Bloodborne HIV: Don't Get Stuck!

Protect yourself from bloodborne HIV during healthcare and cosmetic services

When will governments in sub-Sahara Africa protect citizens from blood-borne HIV?


            Governments across sub-Sahara Africa support programs – testing partners, etc – to reduce people’s risk to get HIV through sex. Similarly, governments promote programs to protect babies by testing pregnant women and, if HIV-positive, giving them anti-retroviral drugs. Those programs cut sexual and mother-to-child transmission.

            But why are so many people still getting HIV?

            There’s a good reason: Governments across sub-Sahara Africa have ignored people’s risk to get HIV from skin-piercing procedures – injections, dental care, infusions, manicures, etc. That risk is more important in some communities and facilities than in others. Is it a risk for you? You can see it’s a risk when you hear of one or more unexplained HIV infections in your community – in children with HIV-negative mothers, in virgin teens, or in adults with no possible sexual exposure to HIV.

            Investigating unexplained infections is the standard way to find and stop blood-borne transmission and thereby to protect patients. Investigations begin with one or more specific unexplained infections by asking where they came from – what clinic, hospital, or cosmetic service might have reused unsterilized skin-piercing equipment? The next step is to test others who visited suspected facilities; if early testing finds more unexplained infections, testing can be extended to thousands or even tens of thousands to find all infected in the outbreak. Investigators can then work backward from who is infected to zero in on the facilities and procedures infecting patients and/or clients.

            Investigations involve a lot of talking and testing, but they are not expensive and do not require experts with rare skills or unusual instruments. The challenges are simple and straightforward: to get healthcare bureaucrats and providers to cooperate; to tell the public that tests are looking for people with HIV from health care; to find and fix dangerous procedures; and, when that’s done, to persuade the public that health care is safe. All that is local. The goal should be prevention not punishment: to educate and alert everyone – providers, patients, clients – to avoid careless errors. A lot of investigating can be done by communities through informal discussions, but thorough investigations need governments to tell their employees – health program managers, hospital staff – to cooperate. In short: African communities and governments can investigate without outside help.

            No government in sub-Sahara Africa has investigated any unexplained HIV infection. By not doing so, governments have not been accountable to their citizens – allowing them to get HIV from risks that could and should be found and stopped. Government misbehavior has contributed to disasters. For example, national random sample surveys in Botswana in 2013 and eSwatini (formerly Swaziland) in 2021 found more than 50% of women aged 35-39 years to be HIV-positive; a national survey in South Africa in 2017 found 39.4% of women aged 35-39 years to be HIV-positive. Findings have been even worse in some local surveys, such as 66.4% of women aged 35-39 years and 59.6% of men aged 40-44 years to be HIV-positive in a community in KwaZulu-Natal in 2014. It is unthinkable that governments in Europe or the Americas – and almost anywhere else in the world – would accept such disasters without doing whatever was necessary to protect men, women, and children.

            Rephrasing the title of this blog: When will African governments be accountable to protect citizens from blood-borne HIV by investigating unexplained infections? Whatever else might contribute to high HIV prevalence, that is something governments can do to protect citizens.

            On the matter of whether or not to investigate, Western governments and institutions have given bad advice to African governments. They have said nothing about investigations as the appropriate and proven response to unexplained HIV infections – such as HIV-positive children with HIV-negative mothers in Kinshasa in 1985. Instead, researchers who saw and reported those 1985 infections advised everyone to accept that unknown numbers of Africans will continue to get HIV from skin-piercing procedures in health care!

            Opposition to investigations is seldom stated baldly, as in this 1994 paper by the head of the World Health Organization’s Global Programme on AIDS and future head of UNAIDS: “The media…has helped to increase public awareness about the dangers of nosocomial [in-hospital] transmission. But the short-term benefits of increased public awareness [after a 1988-89 investigation in Russia] may not always be positive. The current outbreak of diphtheria in Russia… has been blamed in part on publicity surrounding [investigated] nosocomial HIV transmission in southern Russia and other problems in the health-care system, which are thought to have discouraged mothers of young children from seeking immunizations from a health-care system that they perceived to be unsafe.”

            Can governments in sub-Sahara Africa reject Western governments’ advice to ignore and not to investigate unexplained infections? I am hopeful: I see two ongoing economic and geopolitical shifts reducing Western governments’ influence:

*          Economic growth in sub-Sahara Africa year-by-year reduces foreign aid as a percentage of African government budgets. As that percentage drops, African governments are better able to reject donors’ advice.  

*          The world is shifting from a uni-polar to a multi-polar order. BRICS countries (Brazil, Russia, India, China, South Africa), especially, are challenging United States’ (US) efforts to lead a uni-polar world. In 2023, the BRICS partnership attracted new members, while the US squandered international goodwill and influence by financing war in Ukraine and ethnic cleansing in Gaza. China leads one of the new poles in the emerging multi-polar world. Other influential countries, Russia, India, Germany, Japan, Indonesia, etc, may short- or long-term join one or another bloc. A multi-polar world lets aid-receiving countries (most of sub-Sahara Africa) balance one donor against others. This flexibility lets African governments be more accountable to their citizens and less accountable to any donor.  

            I am hopeful these shifts will allow African governments to be more accountable to their citizens and, specifically, to investigate unexplained HIV infections.

How to reach African and global HIV prevention targets?


Introduction: Missing the 2020 target

            In 2014-16 the United Nations (UN), World Health Organization (WHO), and UNAIDS set targets to cut new HIV infections (incidence) globally from 1.9 million in 2015 to 500,000 in 2020 and 200,000 in 2030 (Table 1). The 2030 target is a Sustainable Development Goal (SDG) – to end AIDS by 2030. Those targets promoted interventions that cut HIV transmission, but not enough to reach targets: global incidence in 2020 was 1.5 million, three times the target (Table 1). In 2021, the UN set a new target – 370,000 new infections in 2025 – with the same 200,000 target for 2030.

Table 1: Global HIV incidence targets and estimates, 2015-2030

Incidence targets, estimates2015202020252030
Targets    
 UN, WHO, UNAIDS, and Sustainable Development Goal targets set in 2014-16[1-3] 500,000 200,000*
 Revised UN target set in 2021[4]  370,000200,000
UNAIDS estimates[5]1,900,0001,500,000  
* WHO[1] proposed reducing incidence by 90% from 2.1 million in 2010 to 210,000 in 2030.

            UNAIDS’ 2021-26 strategy focuses on “reducing inequalities”[6,7] so interventions get to more people. That will help, but will it be enough to end AIDS by 2030? This blog considers what has been done and what more could be done to prevent HIV in sub-Sahara Africa and in the rest of the world. Along with continuing current programs, investigating unexplained HIV infections – in children with HIV-negative mothers, in adults with no sexual exposures to HIV – may be essential to end aids by 2030.

Missing targets in sub-Sahara Africa

            Across sub-Sahara Africa, new infections peaked at 2.2 million in 1996. From 1996, incidence fell 3% per year to 1.24 million in 2015 and then slightly faster – 6% per year – to 860,000 in 2021.[5] Following sub-sections consider what happened and what could happen for three transmission paths accounting for most infections in Africa – mother-to-child, heterosexual sex, and skin-piercing medical and cosmetic procedures. After 2000, reductions in mother-to-child and sexual transmission came with policy changes championed by Kevin de Cock at the United States (US) Centers for Disease Control and Prevention (more testing),[8] Jim Kim  at WHO (more anti-retroviral treatment), and Michel Sidibe, UNAIDS Executive Director, 2009-19 (more testing and treatment). After 1999, safer medical injections came with programs led by Yvan Hutin at WHO.[9]

            Mother-to-child: The percentages of HIV-positive women getting drugs to protect their babies  increased from nothing in the mid-1990s to 89% in Eastern and Southern Africa and 61% in Western and Central Africa in 2015, with little change to 2021 (Table 2). Annual HIV incidence in children aged 0-14 years fell circa 300,000 during 1996-2021, accounting for more than a fifth of the overall fall in incidence in sub-Saharan Africa during those years. Further reductions in mother-to-child transmission could cut remaining incidence another 10%-15%. While interrupting mother-to-child transmission is important to protect babies, children’s other risks need attention as well: during 2006-17 national surveys in eSwatini, Mozambique, South Africa, Uganda, and Zimbabwe found 6%-33% of infected babies and young children with HIV-negative mothers.[10]

Table 2: Estimated HIV incidence and interventions in Africa, 1996-2021

Intervention, incidence1996201020152021
Estimated incidence in sub-Sahara Africa, of which2,200,0001,530,0001,240,000860,000
 Adults1,770,0001,240,0001,060,000730,000
 Children aged 0-14 years430,000288,000172,000132,000
Prevention of mother-to-child transmission (PMTCT), % of HIV-positive mothers reached    
 Eastern and Southern Africa0%52%89%90%
 Western and Central Africa0%29%61%60%
Testing: % of HIV-positive adults knowing their status    
 Eastern and Southern Africa<5%63%81%91%
 Western and Central Africa<5%37%54%84%
Treatment as prevention: % of HIV-positive adults with suppressed viral loads    
 Eastern and Southern Africa0%20%47%74%
 Western and Central Africa0%10%26%73%
Note: UNAIDS’ estimated incidence by age groups do not add to UNAIDS’ estimated totals. Sources: UNAIDS.[5]

            Heterosexual sex: The percentages of HIV-positive adults in sub-Sahara Africa knowing their status and having suppressed viral loads hugely increased from low single digits in 1996. By 2015, roughly 3/4ths knew their status and 2/5ths had suppressed viral loads. By 2021, close to 90% knew their status and almost 3/4ths had suppressed viral loads (Table 2).

            While these changes no doubt slashed sexual transmission, their impact on overall-incidence depended on the proportion of incidence in Africa through sex. Continuing high incidence in adults – despite huge increases in testing and treatment – agrees with recent evidence suggesting heterosexual sex accounts for less than half of HIV infections among adults: five studies that sequenced HIV collected from communities in Africa identified sex partners to explain only 0.3%-7.5% of infections; and in eight similar studies a median of 53% of sequence pairs linked people of the same sex (suggesting that contaminated instruments linking people of either sex accounted for more transmissions than male-female sex).[11] Furthermore, since percentages knowing their infections and having suppressed viral loads were already so high in 2021, further increases in these percentages can be expected to have only minor impact on sexual transmission, and even less on overall incidence.

            Condom promotion, an old story, cannot explain differences over time. The potential impacts of other interventions aimed at sexual risks – voluntary medical male circumcision (VMMC) and pre-exposure prophylaxis (PrEP)[12,13] – are limited by how much sexual transmission remains after testing, treatment, and condoms. Furthermore: VMMC programs circumcise many people who would have been circumcised otherwise; many say circumcision harms men; and multiple studies have found women not interested in PrEP (eg, in Kenya[14]).

            Skin-piercing events in health care and cosmetic services: Blood safety (testing blood before transfusing) in sub-Sahara Africa took a leap forward with US support from 2003.[15] Beginning in 1999, WHO’s Safe Injection Global Network (SIGN) campaigned for injection safety. Estimated numbers of unsafe injections per year in sub-Sahara Africa fell by circa 90% from the 1990s to 2011-15  (260-520 million in the 1990s, calculated as 50% of 1-2 injections per person for a population of 520 million[16]; 40 million in 2011-15, calculated as 3.3% of 1.18 injections per person for a population of 910 million[17]).

            More testing of transfused blood and fewer unsafe injections no doubt reduced HIV transmission during health care. However, there are enough other skin-piercing risks in medical and cosmetic services (dental care, infusions, catheters, manicures, tattooing, etc) to explain continuing high levels of blood-borne transmission in Africa.

            The best way to prevent medical and cosmetic procedures transmitting HIV is to investigate unexplained infections. People who see an unexplained infection and realize that whatever caused it may be infecting others can initiate informal local investigations. For example, in 2014, a village leader in Roka, Cambodia, realized he had an unexplained HIV infection. He urged relatives and neighbors to go for tests, which found more infections.[18] Media attention brought a government investigation that identified 242 with HIV from health care. Similarly, a private doctor in Ratodero, Pakistan, identified several unexplained infections in early 2019. Publicity brought a government investigation that by early 2023 had found circa 2,800 children and hundreds of adults with HIV from health care.[19] Publicity from investigations promotes safe practices and warns people to beware blood-borne risks.

            Anal sex among MSM and unsafe injections among IDU: UNAIDS estimates 10% of incidence in sub-Sahara Africa in 2021 was in MSM and IDU (7% in MSM including transgender women born male; and 3% in IDU). The interventions UNAIDS proposes for MSM and IDU (treatment as prevention, PrEP, condoms, sterile injection equipment, etc.) are on target. However, impact on overall incidence may be small, not only because working with MSM and IDU is challenging, but also because 10% may overstate their share of Africa’s incidence. If MSM and IDU had 10% of Africa’s infections, per capita incidence from those risks in Africa (0.0075%/year, calculated as 10% of 860,000 infections in 1.12 billion people) would higher than in the rest of the world, which seems unlikely (0.006%/year, calculated as 62% of 640,000 infections in 6.65 billion people).[20,21]

Missing targets in the rest of the world

            In the rest of the world (excluding sub-Sahara Africa) new HIV infections in adults peaked in the 1990s and then fell circa 4% per year to 2010. During 2010-21, adult incidence fell more slowly, at 0.3% per year, with major differences by regions (eg, falling in Asia and the Pacific, but increasing in Eastern Europe and Central Asia). Following subsections consider interventions and incidence for five risks, four of which UNAIDS addresses (mother-to-child, MSM, heterosexual sex, and IDU) and a fifth that UNAIDS ignores (medical and cosmetic skin-piercing procedures).

Table 3: HIV incidence and interventions in the rest of the world, 1996-2021

Incidence, interventions201020152021
Estimated adult incidence610,000600,000590,000
Testing: % of HIV-positive adults knowing their status (three regions with most infections) 53%, 73%, no estimate62%-82%
Treatment as prevention: % of HIV-positive adults with suppressed viral loads (three regions with most infections) 20%, 45%, no estimate48%-64%
Note: Adult incidence adds UNAIDS’ estimates for each regions outside sub-Sahara Africa. Source: UNAIDS.[5]

           Mother-to-child: According to UNAIDS, outside sub-Sahara Africa, incidence in children aged 0-14 years was 3% of total incidence for all ages in 2021. In the two regions that account for most children’s incidence, Asia and the Pacific and Latin America, 49% and 63%, respectively, of HIV-positive women got drugs to protect their babies in 2021, with little change from 2015. Reaching and treating more HIV-positive pregnant women could bring modest reductions in overall incidence.

            Sex, including MSM and heterosexual sex: UNAIDS estimates that 82% of HIV incidence outside sub-Sahara Africa in 2021 came from sex – 44% in MSM (including transsexuals) and 38% in heterosexuals. Most of those infections come from three regions: Asia and the Pacific, Eastern Europe and Central Asia, and Latin America.

            For those three regions, UNAIDS estimates 48%-64% of HIV-positive adults had suppressed viral loads in 2021 (Table 3). Because people with suppressed viral loads almost never transmit through vaginal or anal sex, increasing percentages of adults with suppressed viral loads no doubt reduced sexual transmission during 2010-2021. However, since overall incidence fell only 3% during that period, UNAIDS may have been overestimating sexual transmission. Because countries with the best information on HIV risks (in Western Europe, North America, and East Asia) report large percentages of infections in MSM, overestimates of HIV from sex are more likely for heterosexuals than for MSM. Ignoring problems with estimates, some further reductions in sexual transmission could be achieved by extending treatment, especially to MSM with new infections.

            IDU: UNAIDS estimates IDU accounted for 18% of incidence in the rest of the world, with big differences between the three regions with the most incidence — 4% in Latin America, 12% in Asia and the Pacific, and 39% in Eastern Europe and Central Asia. Cross-country comparisons suggest these rates can be reduced, but proven interventions (eg, getting IDUs to use sterile injection equipment, opioid treatment) can be hard to implement due to controversies about policies and difficulties reaching and working with IDUs.

            Skin-piercing events in health care and cosmetic services: Where most infections are in MSM and IDUs, several times more men than women are infected. For example, across Western and Central Europe and North America, 3.2 men are infected for every woman (according to UNAIDS estimates for 2021).[5] Even higher ratios are common in countries with low HIV prevalence; for example, Australia has a sex ratio of 7.1 and 0.1% adult prevalence.

            On the other hand, low ratios of men to women infected in many countries outside sub-Sahara Africa suggest many women and some men are getting HIV from non-IDU skin-piercing procedures. The two regions that account for roughly 2/3rds of infections outside sub-Sahara Africa have much lower male-female ratios compared to Western Europe and North America. In Eastern Europe and Central Asia, with 1.1% adult prevalence, the sex ratio is 1.9 overall, but lower in many countries, including 1.0 in Ukraine. Similarly, the sex ratio in Asia and the Pacific is 1.7, but lower in many countries, including 0.7 in Papua New Guinea and 0.9 in Cambodia. The Caribbean region, with 1.2% adult prevalence (the highest outside sub-Sahara Africa) has a sex ratio of 1.0.

            UNAIDS’ silence about HIV infections from unsafe health care ignores a lot of evidence. As of 2011-15, WHO experts estimated that 6.7% of injections in Southeast Asia, 2.9% in Europe, and 9.8% in the Eastern Mediterranean were unsafe.[16] During 1986-2021, scores of investigations outside sub-Sahara Africa uncovered small to large outbreaks from unsafe medical procedures, including twelve with more than 100 to an estimated 100,000 HIV infections.[10]

Conclusion: Africa could lead

            Considering the annual rate at which HIV incidence has been falling since 2015, there is little chance that targets – 370,000 new infections in 2025 and 200,000 in 2030 – will be achieved with UNAIDS’ current strategy. Much of the potential impact from treatment and testing has already been realized. Other interventions in UNAIDS’s strategy will help, but not enough.

            To meet targets, something must be done about HIV transmission through skin-piercing procedures in health care and cosmetic services. The best way to reduce such transmission is to investigate unexplained infections. Based on experiences to date, WHO, UNAIDS, donors, and many governments are unlikely to lead. If and when the African general public takes the lead to investigate unexplained infections in several communities, it will likely take several more years for public awareness to roll back blood-borne transmission in Africa. Investigations in Africa could encourage the public and governments in other regions to investigate as well. If investigations in Africa begin in the next several years, and if other investigations and programs progress, HIV incidence around the world could fall to 200,000 by 2030 or not long after. Without investigations, targets are out of reach.

References

1. WHO. Accelerating progress on HIV, tuberculosis, malaria, hepatitis and neglected tropical diseases. A new agenda for 2016 – 2030. Geneva: WHO, 2015. Available at: https://apps.who.int/iris/bitstream/handle/10665/204419/9789241510134_eng.pdf  (accessed 12 May 2023).

2. UNAIDS. Fast-Track: ending the AIDS epidemic by 2030. Geneva: UNAIDS, 2014. Available at: https://www.unaids.org/sites/default/files/media_asset/JC2686_WAD2014report_en.pdf

3. UN General Assembly. Political Declaration on HIV and AIDS: On the fast-track to accelerate the fight against HIV and to end the AIDS epidemic by 2030 (General Assembly resolution 70/266). New York: UN, 2016. Available at: https://www.unaids.org/sites/default/files/media_asset/2016-political-declaration-HIV-AIDS_en.pdf (accessed 12 May 2023).

4. United Nations. Political Declaration on HIV and AIDS: ending inequalities and getting on track to end AIDS by 2030. New York: UN, 2021. Available at: https://www.unaids.org/sites/default/files/media_asset/2021_political-declaration-on-hiv-and-aids_en.pdf.

5. UNAIDS. HIV estimates with uncertainty bounds 1990-2021. Geneva: UNAIDS, 2022. Available at: https://www.unaids.org/en/resources/documents/2022/HIV_estimates_with_uncertainty_bounds_1990-present (accessed 12 May 2023).

6. UNAIDS. Global AIDS Strategy 2021-2026. Geneva: UNAIDS, 2021. Available at: https://www.unaids.org/sites/default/files/media_asset/global-AIDS-strategy-2021-2026_en.pdf (accessed 13 May 2023).

7. UNAIDS. In Danger: UNAIDS global AIDS update 2022. Available at: https://www.unaids.org/sites/default/files/media_asset/2022-global-aids-update_en.pdf (accessed 19 May 2023).

8. De Cock KM, Mbori-Ngacha D, Marum E. Shadow on the continent: public health and HIV/AIDS in Africa in the 21st century. Lancet 2002; 360: 67-71.

9. WHO. Safe Injection Global Network (SIGN): Initial meeting report, October 4-5, 1999. Geneva: WHO, 2000. Available at: https://apps.who.int/iris/bitstream/handle/10665/66232/WHO_DCT_00.1.pdf (accessed 25v May 2023).

10. Gisselquist D. Stopping Bloodborne HIV: investigating unexplained infections. London: Adonis & Abbey, 2021. Available at: https://sites.google.com/site/davidgisselquist/stoppingbloodbornehiv   (accessed 29 December 2022).

11.  Gisselquist D. Recognizing and stopping blood-borne HIV. SSRN [internet] 2022. Available at: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4174723 (accessed 23 January 2023).

12. UNAIDS, WHO. Uneven progress on the voluntary medical male circumcision. Geneva: UNAIDS and WHO, 2022. Available at: https://cdn.who.int/media/docs/default-source/hq-hiv-hepatitis-and-stis-library/who-unaids-male-circumcision-progress-brief-2022.pdf?sfvrsn=2852eedf_1&ua=1 (accessed 14 May 2023).

13. WHO. Global State of PrEP. Geneva: WHO, 2022. Available at: https://www.who.int/groups/global-prep-network/global-state-of-prep#:~:text=There%20were%20about%201.6%20million,in%20eastern%20and%20southern%20Africa. (accessed 14 May 2023).

14. Kinuthia J, Pintye J, Abuna F, et al. Pre-exposure prophylaxis uptake and early continuation among pregnant and post-partum women within maternal and child health clinics in Kenya: results from an implementation programme. Lancet HIV2020; 7: e38-e48.

15. Mili FD, Teng Y, Shiraishi RW, et al. New HIV infections from blood transfusions averted in 28 countries supported by PEPFAR blood safety programs, 2004‐2015. Transfusion 2021; 61: 851-861. Available at: https://onlinelibrary.wiley.com/doi/epdf/10.1111/trf.16256 (accessed 19 May 2023).

16. Kane A, Lloyd M, Zaffran M, et al. Transmission of hepatitis B, hepatitis C and human immunodeficiency viruses through unsafe injections in the developing world: Model-based regional estimates. Bull World Health Organ 1999; 77: 801-7. Available at https://pubmed.ncbi.nlm.nih.gov/10593027/ (accessed 16 May 2023).

17. Hayashi T, Hutin YJ-F, Bulterys M, et al. Injection practices in 2011- 15: a review using data from the Demographic and Health Surveys (DHS). BMC Health Serv Res 2019; 19: 600. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712605/pdf/12913_2019_Article_4366.pdf (accessed 16 May 2023).

18. Sarath E. Ministry of Health, Cambodia. 24 December 2014. HIV cases in Sangke district, Battambang. Available at: http://www.cdcmoh.gov.kh/97-hiv-cases-in-sangke-district-battambang

19. Bhatti MW. Dozens getting HIV positive on weekly basis in four Sindh talukas. Geo News [internet] 7 March 2023. Available at: https://www.geo.tv/latest/474811-hiv-outbreak-peaks-in-sindh-as-more-and-more-children-test-positive (accessed 4 May 2023).

20. UNAIDS. Core epidemiology slides. Geneva: UNAIDS, 2022. Available at: https://www.unaids.org/en/resources/documents/2022/core-epidemiology-slides (accessed 17 May 2023).

21. UN Population Division. World Population Prospects 2022. New York: UN, 2022. Available at: https://population.un.org/wpp/ (accessed 19 May 2023).

Misinforming Africans about HIV led to AIDS disasters


In the early 1980s, AIDS was first recognized among men-who-have-sex with men (MSM) and injection drug users (IDU) in the United States (US). Because hepatitis B was common in both groups but rare in the US general population, it was apparent almost immediately that whatever caused AIDS threatened groups at high risk for hepatitis B. That included the general population in Africa, where 70%-90% of adults had current or resolved hepatitis B infection.[1]

The first studies using HIV tests in Africa in the mid-1980s found that Africans were getting HIV from blood exposures and sex. Experts debated how much came from each risk, but what they did not do is give Africans the information they needed to address either one of them. Instead, experts bombarded them with misinformation, telling them almost all adults’ infections came from sex, a fabrication inconsistent with evidence.

Not warning Africans about HIV from health care

WHO assured Africans their health care was safe, even though WHO and donor governments warned staff to avoid health care in Africa. In Mexico, Russia, Romania, and India in the late 1980s government investigations of unexplained infections not only found and stopped large outbreaks from medical procedures but also warned – educated – the public  to beware blood-borne risks. But no government in sub-Sahara Africa similarly investigated any unexplained infection, and no international organization or donor recommended investigations in Africa.[2]

Not letting Africans see who was infected so they could avoid sex risks

WHO, donors, and governments did not make HIV tests easily available. Across most of Africa, HIV tests were difficult to get until some years after 2000. This was deliberate: WHO tied tests to counseling and urged caution rather than action[3]: “National AIDS programmes that decide to develop voluntary testing and counselling services where none now exist should proceed cautiously by initiating and evaluating a trial project.” WHO staff opposed access to home-based tests, denying (despite evidence) that testing had a role to play in preventing heterosexual transmission.[4]

Hence, few people knew if they or their sex partners were infected. Not until 2012, 25 years after low cost rapid tests were developed, did WHO recommend couple counseling to allow people to see their sex risks.[5] In 2016, four years later, WHO recommended home-based self-testing kits (which had been available from the 1990s) and helping HIV-positive adults inform and warn their sex partners.[6]

Lying about HIV sexual transmission

Since WHO and donors did not want to admit HIV from health care, they had no choice but to blame sex. Not later than 1988, WHO and donors invented and spread the lie that almost all adults’ infections in Africa came from sex. Yes, sex was a risk; but the claim that almost all adults’ infections came from sex was contradicted by evidence available at the time.[7] But it was a useful lie, distracting attention from infected children with HIV-negative mothers, infected virgins, and infected teens and adults with one HIV-negative lifetime sex partner. Moreover, blaming sex was useful in another way: The lie silenced people who had gotten HIV from health care by threatening them with disbelief and suspicions of sexual misbehavior if they talked about their infections. Blaming sex became an industry that was bad for Africans’ health but made a lot of money for donor, government, and NGO health staff. It is a testament to families in Africa that most husbands and wives trusted each other and stayed together in the face of experts’ lies about sexual transmission.

Bad policies allowed AIDS disasters

These bad policies have harmed millions. As of 2021, the percent of adults HIV-positive (adult HIV prevalence) ranged from 2.3% to 27.9% in 17 countries in sub-Sahara Africa, whereas outside sub-Sahara Africa, only 0.3% of adults were infected, and no country had as many as 2% of adults HIV-positive. Outcomes have been even worse for women: across sub-Sahara Africa 1.7 women are HIV-positive for every infected man (UNAIDS’ 2021 estimates: 15.2 to 8.9 million infections), whereas outside the region, 1.8 men were infected for every woman (8.1 to 4.5 million).[8]

References

1. Kiire CF. The epidemiology and prophylaxis of hepatitis B in sub-Saharan Africa: a view from tropical and subtropical Africa. Gut 1996; 38: S5-S12. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1398049/pdf/gut00509-0010.pdf (accessed 19 May 2023).

2. Gisselquist D. Stopping Bloodborne HIV: investigating unexplained infections. London: Adonis & Abbey, 2021. Available at: https://sites.google.com/site/davidgisselquist/stoppingbloodbornehiv   (accessed 29 December 2022).

3. Global Programme on AIDS. Statement from the consultation on HIV testing and counselling for HIV infection, Geneva 16-18 November 1992. Geneva: WHO, 1993. Available at: https://apps.who.int/iris/handle/10665/58905 (accessed 23 May 2023).

4. Mertens TE, Smith GD, Van Praag E. Home testing for HIV. Lancet 1994; 343: 1293. Available with pay-wall at: https://www.thelancet.com/journals/lancet/issue/vol343no8908/PIIS0140-6736(00)X8037-3 (accessed 23 May 2023).

5. WHO. Guidance on couples HIV testing and counselling including antiretroviral therapy for treatment and prevention in serdiscordant couples. Geneva: WHO, 2012. Available at: https://apps.who.int/iris/handle/10665/44646 (accessed 19 May 2023).

6. WHO. Guidelines on HIV self-testing and partner notification: supplement to consolidated guidelines on HIV testing services. Geneva: WHO, 2016. Available at: https://apps.who.int/iris/handle/10665/251655 (accessed 22 May 2023).

7.  Gisselquist D, Potterat JJ, Brody S, Vachon F. Let it be sexual: how health care transmission of AIDS in Africa was ignored. Int J STD AIDS 2003; 14: 148-161. Available at: https://www.cirp.org/library/disease/HIV/gisselquist1/gisselquist1.pdf (accessed 23 May 2023).

8. UNAIDS. HIV estimates with uncertainty bounds 1990-2021. Geneva: UNAIDS, 2022. Available at: https://www.unaids.org/en/resources/documents/2022/HIV_estimates_with_uncertainty_bounds_1990-present (accessed 12 May 2023).

HIV Own Goals – LGBTQ in Uganda


Shaming people for their alleged sexual behavior has deadly consequences for everyone infected with HIV and anyone engaged in behaviors said to result in HIV transmission, or claimed to be so engaged. Given the weight of evidence against the sexual behavior paradigm of HIV transmission (which, mysteriously, only operates in high prevalence African countries), why does the industry still use it to prop up every campaign?

When HIV was identified in several US cities in the 1980s, it was mainly found among men who had sex with men (MSM), injecting drug users (IDU) and people who received blood products or transfusions that contained the virus. Now, 40 years later, the largest proportion of people in those same US cities with HIV are MSM, with IDUs a distant second.

A few years later, when HIV started to spread rapidly in African countries, such ‘high risk groups’ did not account for the highest proportion of HIV transmissions. Rather, prevalence was higher among people who were not MSM or IDUs. Prevalence was high among a group often referred to as commercial sex workers (CSW), or just as sex workers. But it’s not clear that these were coherent groups of people who self-identified as sex workers, or if they were assumed to be sex workers by those collecting data, on the basis of their HIV status.

In fact, many of the people infected with HIV early on in the epidemic in African countries which subsequently experienced the highest prevalence rates in the world were more closely associated with healthcare than with high levels of ‘risky’ sexual behavior. Women who gave birth in health facilities, even clients of STI facilities, were infected in very large numbers. And that is still the case. Most people infected do not engage in any kind of risky behavior. Their infections are unexplained by the prevailing paradigm.

From the 1980s onwards, very high transmission rates in African countries tended to be found in cities, within the compounds of employers of large numbers of people, such as mines and other labor-intensive industries, close to well-developed infrastructures, in the vicinity of large hospitals, and in areas and countries where healthcare was accessible to all or most people. Examples of this are South Africa, Botswana, Zimbabwe, Zambia, Swaziland and Lesotho, mostly in Southern or Eastern Africa.

In contrast, most countries, even on the African continent, experienced lower transmission rates. Transmission rates in countries in the north of the continent, especially those on or overlapping with the Sahara, were, and still are, lower than in many US cities. Isolated areas, places where healthcare facilities didn’t exist, or were not used by most people, remained relatively free of HIV. Even in countries where HIV prevalence was very high in some areas, it remained low in isolated areas. Examples are Kenya, Tanzania, Uganda and others, where there are only a few high prevalence hostpots.

So why did the HIV industry play the LGBTQ and promiscuity cards in countries where neither MSM nor sexual behavior seemed to be the biggest risk for HIV transmission? If the industry wanted people in African countries to reduce transmission, they would have had more success if they had encouraged healthcare facilities to figure out why they seemed to be the source of a lot of infections, perhaps a majority. The funders of healthcare (and HIV) would have been ideally placed to insist that an appropriate proportion of funding be spent on healthcare safety, or to withdraw the funding if it was not.

Some transmission may have been a result of sexual behavior, although probably not the sexual behavior of most people, which tended to be conservative. And MSM sex does occur, despite western ‘experts’ initially claiming that it was rare in ‘African’ countries. But successive Modes of Transmission Surveys have shown that infections among these higher risk groups make up only a small proportion of total infections.

All people infected with HIV, young women, men, married or single, those engaged in sex work, or alleged to be so engaged, every MSM, including those alleged to be gay, prisoners and almost everyone else in high HIV prevalence countries suffer the consequences of the continued association of high HIV prevalence with promiscuity and with MSM.

An article in SciDev.net trots out the tired old fictoids, about homophobia threatening ‘HIV progress’, about HIV prevalence being “higher in countries with laws that criminalize homosexuality”, and the insinuation that this “could impact foreign aid to Uganda”.

The deep homophobia that we see in Uganda and other high HIV prevalence countries didn’t exist in the 1980s. The bill (the ‘Bahati Bill’) that initially proposed lengthy sentences and even the death penalty was supported by US evangelical Christians. The spite towards ‘sex workers’ and people who were perceived as being promiscuous was a continuation of long-held prejudices about ‘African’ promiscuity, dating back to the Eugenicists, and beyond.

The worst HIV epidemic in the world is in South Africa, where as much as 20% of the global population of HIV positive people live. Yet, homosexuality is not criminalized there. In contrast, HIV prevalence in most North African countries is lower than that found in many western countries and in US cities where HIV prevalence has been high since the 1980s, although homosexuality is criminalized in most North African countries. Many countries where homosexuality is criminalized are also countries with low or very low HIV prevalence, such as those in the Middle East, Central Asia and elsewhere.

Numerous Aids Indicator Surveys and Demographic and Health Surveys show that most people in all countries, on every continent, engage in relatively low levels of sex, ‘risky’ or otherwise. Some people engage in high levels of sex, sometimes ‘risky’ sex, in every country. Among MSM, only some are ‘promiscuous’ and many take precautions to avoid infecting others or being infected with HIV. Outside of sub-Saharan Africa, people engaged in sex work are unlikely to be infected with HIV unless they are also IDUs or have some other, non-sexual risk.

Playing the promiscuity and LBGTQ cards is what drives the increasing homophobia seen in countries like Uganda. Obama and Cameron threatened to reconsider HIV funding after the Bahati Bill was proposed and Museveni, predictably, said they could keep their funding. This SciDev.net article seems to be reiterating that threat. It was the HIV industry that built itself up around prejudices and issues that the legacy and trade media will always report assiduously.

If SciDev.net and the HIV industry in general are genuinely interested in addressing HIV transmission, after dithering for 4 decades, they could start asking some of these questions that have long demanded an answer. If only some HIV transmission is accounted for by sexual behavior, including MSM sex, how is the rest to be accounted for? If that question is not answered then HIV transmission will continue through the industry’s next ‘target’, 2030. 

High HIV prevalence and unknown risks for African Americans, especially women


Abstract

In the United States, HIV prevalence and incidence for African Americans (Blacks) are much higher than for non-Hispanic Whites. This is especially so for women. Differences remain unexplained more than 35 years after they were recognized in the 1980s. The Centers for Disease Control and Prevention (CDC) collects information on risks for persons diagnosed with HIV in Adult HIV Confidential Case Report Forms. In 2014, the last year the CDC reported raw data from collected Forms, more than half of Black women and more than a quarter of Black men were reported with no identified risk. Moreover, in 2007, the last year the CDC disclosed information about partners of cases reported with heterosexual risk, more than a third of HIV-positive Black women were reported with heterosexual risk despite limited and questionable evidence about partners. Currently, the CDC estimates percentages of HIV-positive adults with various risks using a model that assigns men and women to risks based on factors such as ethnicity. Such estimates hide the CDC’s ignorance about risks. Multiple risks, including, for example, contaminated instruments in healthcare and cosmetic services and sex with bisexual males may be contributing to high HIV prevalence among Blacks, especially women. Research is warranted.

High HIV prevalence and low sex ratio of infections in US Blacks

                The CDC reports 1.27% of Black and 0.18% of White adults (aged ≥13 years) living with reported HIV infection at end-2019 (Table 1). Much higher HIV prevalence for Blacks compared to Whites was due to decades of higher incidence among Blacks. For women, differences have narrowed: the percentage of Black women with new infections in 2019 was 12.5 times the percentage of White women with new infections, whereas HIV prevalence (old and new infections) among Black women was 17.2 times greater than for White women. For Black men, differences may be increasing: in 2019, the percentage of Black men reported with new infections was 8.1 times greater than for White men, whereas HIV prevalence among Black men was 5.6 times greater than for White men.…

                To compare HIV prevalence in US Blacks to prevalence in other countries, CDC’s reports of Blacks living with reported infections must be adjusted to include persons not diagnosed and reported. In 2019, CDC estimated 13.4% of HIV-positive Black adults in the US were unreported (Table 9 in reference[6]).

                Adjusting for unreported infections, an estimated 1.47% (= 1.27/0.866) of Black adults were HIV-positive in 2019. Estimated 1.47% HIV prevalence among Blacks aged ≥13 years exceeds UNAIDS’ estimated 2021 HIV prevalence in adults (aged ≥15 years) in all regions except Eastern and Southern Africa with 6.2% HIV prevalence: Asia and Pacific, 0.2%; Middle East and North Africa.

Discussions [Conclusions]

                Based on the CDC’s latest reports of raw data from submitted Case Report Forms, the CDC’s estimated risks for more than half or even two-thirds of HIV-positive Black women are based on no or insufficient evidence (Tables 3 and 4, above). As for Black men, the CDC’s estimates may be assigning more than a third of infected men to risks despite no or insufficient evidence. Because the CDC stopped reporting raw data from Case Report Forms in 2007 (heterosexual risks) and 2014 (no identified risks), raw data reported in Tables 3 and 4 may have changed. In any case, research is required to explain (and thereby prevent) HIV risks among Blacks, especially Black women. One recent ray of hope is that the thousands of HIV sequences generated every year (to find antiretroviral escape mutations) may also help to track epidemiologic linkages.

Note

The abstract that begins this post is available from SSRN at: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4317106. The several paragraphs after the abstract are quotes from the paper posted and available at SSRN through the above link. This link might work as well: https://deliverypdf.ssrn.com/delivery.php?ID=020102027024077106120117072094019014122017071012062030101001070122113064067007121029056029020062102033001068100026093113121114015072091036076110092001004019068066067085066040013005067075003108113106119077101110124121072000101089094127090093020074003072&EXT=pdf&INDEX=TRUE

UNAIDS Knows What’s Best


Winnie Byanyima, head of UNAIDS, wrings her hands about racism and stigma, and the title of the article points the finger at ‘Big pharma’. But that’s not quite accurate. Big pharma will take money from anyone, not just people in sub-Saharan Africa (SSA). The characterization of HIV as a primarily sexually transmitted virus in sub-Saharan Africa is one of the main sources of stigma. The consequent grouping of HIV positive people according to their assumed or alleged sexual behavior is one of the main sources of racism and sexism. The source of the prejudice is institutions, the UN, development finance, academia and others. 

The executive summary of the 2022 Global Aids Update claims (in a pie chart, page 15) that 97% of all HIV positive people in SSA were infected through sexual contact. Over 40% are said to be infected through sex work, either because they are (alleged) sex workers or (alleged) clients of sex workers. And a whopping 49% are part of the ‘remaining population’. Which means, if they were infected sexually, they must engage in extraordinary levels of ‘risky’ sex (although it looks as if UNAIDS can’t convincingly explain how they were infected, they just publish data attributing it to some kind of sex). 

The population of HIV positive people in SSA is 1.94%, overall (23,500,000 people living with HIV; 1.21b people). Many HIV positive people are either not sexually active, not engaging in any kind of sexual contact with a HIV positive person, or only engage in ‘safe’ sex. A relatively difficult to transmit virus, at least sexually, infects about 23,500,000 people, mostly in a few parts of several countries, the vast majority of those being in about 10 countries in eastern and southern Africa. So why target the entire 1.18b people in SSA when you could target these ‘hyperendemic’ hotspots? (Of course, 1.18b is a much bigger market than just 2% of that, so that’s a good reason.) 

But UNAIDS (and therefore Big pharma, BINGOs, funding, healthcare, and anyone else with a share in the industry) target those who are infected with HIV, regardless of whether they are ‘key populations’. (In case this is beginning to sound like a circular argument, I can assure you that it is.) Being HIV positive is used as a proxy for ‘engaging in some kind of risky sex’; and engaging in sex of any kind, or being assumed to do so, attracts the blanket behavior change communications and other finger-wagging interventions that many people in SSA have grown up with. That means the entire sexually active population of SSA is considered to be ‘at risk’. 

When Big pharma came up with their ‘Pre-exposure prophylaxis’, (PrEP, the use of antiretrovirals by HIV negative people to reduce the risk of being infected), they targeted anyone engaging in sex, or alleged to be engaging in sex. PrEP was designed for people who identified themselves as belonging to a group that faced a higher risk of HIV transmission. It was developed in wealthy countries, where the behaviors involved are not as deeply stigmatized as they are in many parts of SSA. Big healthcare came up with mass male circumcision because the US believes it is ‘hygienic’ (with all the racist overtones of that word). Big NGOs were already deeply involved in ‘behavior change’ programs, which date back to a time when eugenics was openly referred to as science. 

But there is something very simple that Byanyima, UNAIDS and others in the industry can do: they can target the places or broader environments where all the bigger sub-epidemics can be found. They can consider the circumstances in which people live that may make them more susceptible to infection with HIV or other serious diseases. HIV positive people in the worst hit hotspots have things in common that have nothing to do with their individual sexual behavior. Cities, places with relatively good infrastructure, accessible and widely accessed healthcare facilities, high population density areas, big employers and various other factors have been closely associated with some of the highest rates of HIV transmission. 

In contrast, most people in most countries engage in some kind of sexual behavior, some in high levels of sexual behavior, and some in high levels of ‘risky’ sexual behavior. But there is little evidence that sexual behavior patterns are unprecedented in SSA, even less so in HIV hotspots. Pointing the finger at sex and implying that being HIV positive strongly suggests that people’s HIV status is a result of their individual sexual behavior is the source of the stigma associated with HIV. Big pharma and other players in the industry merely adopted UNAIDS’s and academia’s scattergun approach. If you brand the entire population of a sub-continent as promiscuous, you can’t then qualify your actions by adding that you do so in a completely non-stigmatizing way. 

More women than men are infected with HIV in SSA (although far more men than women are infected outside SSA). So, the pie chart claiming that 97% of HIV positive people were infected through their own individual sexual behavior reflects the anti-woman and institutionally sexist strategy of UNAIDS and the industry. African men are stigmatized as predatory. Some men may be, but predatory behavior is not confined to SSA, nor to high HIV prevalence hotspots. UNAIDS and the rest of the industry, including academia, and legacy media who depict HIV as a predominantly sexually transmitted virus, but only in SSA, are upholders of this stigma, institutionalized sexism and racism. 

UNAIDS has been around for nearly thirty years and was set up by people who had already worked with HIV for the 10 years since it was identified. The groups most affected by HIV in the 1980s in SSA were often self-identified as sex workers, sex worker clients, and the like. These are groups that had been targeted by healthcare practitioners for decades to address sexually transmitted infection and contraception. Other groups that were infected with HIV early on include women giving birth in healthcare facilities, antenatal care clinics and similar. Some of the biggest outbreaks of the mid to late 80s and early 90s are the hyperendemic hotspots of today. 

UNAIDS and other institutions that have been working with HIV in SSA from early on, or from the very beginning, know better than anyone how misplaced the stigma is. They know more than most about the conditions people live in, and what their health determinants are. They collect the figures showing that individual sexual behavior cannot account for any of the massive rates of HIV transmission that occurred after HIV was identified (not before). If anyone knows what happened, UNAIDS and all the other institutions working in the epicenters of HIV in SSA should, because they were there. A lot of these epicenters are healthcare facilities. They are still operating and can still be investigated. 

Stigmatize or prevent?


As a US citizen, my tax dollars promote the lie that almost all HIV infections in adolescents and adults in Africa come from sex. Experts who should know better began this lie in the 1980s and have repeated it for decades. The lie ignores early[1] and recent[2] evidence that only a minority of infections come from sex. Most who repeat the lie intend no damage because they believe it.

Whether a deliberate lie or repeated by those who don’t know better, the lie stigmatizes and hurts HIV-positive people. For example:

Beginning in 2015, USAID’s DREAMS program in 10 African countries proposed to reduce new HIV infections in women aged 15-24 years by 40%. DREAMS focused exclusively on sexual risks.[3] By ignoring bloodborne risks, the DREAMS program stigmatized HIV positive women, implying their infections came from sexual behavior, and implicitly charged infected virgins with lying: you’re a slut and a liar. Many young HIV-positive women in the 10 DREAMS countries are self-reported virgins. Since only a small minority of infections in young women in Africa come from sex[4], DREAMS was ill-designed to protect them: predictably, an assessment of Dreams’ impact in South Africa, looking at almost 2,000 women, found that exposure to DREAMS’ programs “was not associated with measurable reductions in risk of sexually acquiring or transmitting HIV.”[5]

WHO in 2012[6]  recommended “Couples and partners should be offered voluntary HIV testing and counselling with support for mutual disclosure.” The document recommended counseling couples about sexual risks but not bloodborne risks. Silence about bloodborne risks encouraged HIV-negative spouses to suspect their infected partners got HIV from sex. Such suspicions threatened relationships and families.

WHO in 2016[7] recommended: “Voluntary assisted partner notification services should be offered as part of a comprehensive package of testing and care offered to people with HIV.” As in 2012, WHO in 2016 recommended counseling couples about sexual risks but said nothing about bloodborne risks. As noted above, silence about bloodborne risks threatened relationships and families. 

WOMENKIND Worldwide defines sexual bullying to include (page 3 in reference [8]) “…spreading rumours about someone’s sexuality or sexual experiences they have had or not had…” The lie that almost all HIV comes from sex promotes such bullying, encouraging people to suspect and spread rumours about the sexual behavior of HIV-positive adolescents and adults in their families and communities.

Not preventing HIV

Warning only about sex risks not only stigmatizes HIV-positive adolescents and adults, it also undermines HIV prevention by encouraging HIV-negative people to ignore avoidable skin-piercing risks. The DREAMS program, for example, by focuses young women’s attention on sex encourages them to overlook bloodborne risks, which are their bigger risk (see Table 6.1, Figure 6.3, and associated text in reference [4]) Messages that warn about both risks would give people the information they need to avoid HIV.

References

1. Gisselquist D, Potterat JJ, Brody S, Vachon F. Let it be sexual: how health care transmission of AIDS in Africa was ignored. Int J STD AIDS 2003; 14: 148-161.

2. Gisselquist D. Recognizing and stopping blood-borne HIV. SSRN [internet] 2022. Available at: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4174723 (accessed 23 January 2023).

3. Saul J, Bachman G, Allen S, et al. The DREAMS core package of interventions: A comprehensive approach to preventing HIV among adolescent girls and young women. PLOS ONE, 7 December 2018. Available at https://doi.org/10.1371/journal.pone.0208167 (accessed 22 January 2023).

4. Gisselquist D. Stopping bloodborne HIV: investigating unexplained infections. London: Adonis & Abbey, 2021. Available at: https://sites.google.com/site/davidgisselquist/chpt6sbh (accessed 24 January 2023).

5. Nondumisoa M. Kathya B, Natsayia C, et al. The association of exposure to DREAMS on sexually acquiring or transmitting HIV amongst adolescent girls and young women living in rural South Africa. AIDS 2022; 36: S39-S49.  Available at: https://journals.lww.com/aidsonline/Fulltext/2022/06151/The_association_of_exposure_to_DREAMS_on_sexually.5.aspx (accessed 22 January 2023.

6. WHO. Guidance on couples HIV testing and counselling including antiretroviral therapy for treatment and prevention in serodiscordant couples: recommendations for a public health approach. Geneva: WHO, 2012. Available at: #14 COUPLES HIV TESTING AND COUNSELLING (who.int) (accessed 13 January 2023).

7. WHO. Guidelines on HIV self-testing and partner notification: supplement to consolidated guidelines on HIV testing services. Geneva: WHO, 2016. Available at: https://apps.who.int/iris/bitstream/handle/10665/251655/9789241549868-eng.pdf (accessed 22 January 2023).

8. WOMANKIND Worldwide. Stop sexual bullying: preventing violence, promoting equality, act now. London: WOMANKIND Worldwide, 2010.

After investigating unexplained infections, what’s left for HIV prevention research?


Here’s a proposal: Manage prevention research to prevent HIV

Design and manage HIV prevention research to prevent new HIV infections in participants. At the outset:

Warn participants about bloodborne risks. To help defray those risks: (a) advise participants how to recognize dangerous procedures; and (b) find out where they go for skin-piercing procedures (clinics, hospitals, cosmetic service providers, etc) and then visit those facilities to assess their efforts to prevent HIV transmission through skin-piercing procedures and, if deficient, advise them what to do better.

Warn participants about sex risks. To help defray sex risks: (a) trace and test sex partners, and if any are found HIV-positive, arrange couple counseling to warn participants at risk; and (b) distribute self-testing kits.

Ask participants to return to the study clinic  every three months for HIV tests and questions about risks. If a participant is found with a new infection despite all the advance advice and attention to possible risks, prevention didn’t work. Researchers, in other words, failed to protect them.

To find out what went wrong – to determine the source of the infection – ask about the participant’s possible sex and blood exposures in recent months. Then (re)trace and (re)test sex partners, and (re)visit facilities that provided skin-piercing procedures. If no sex risk is identified, test others attending suspected skin-piercing facilities to see if any facility infected others and thereby to zero in on the source.

After 6-9 months or so, once research staff have determined what failed to allow any new infections and have adjusted advice to participants and to health care and cosmetic service providers, the rate of new HIV infections should fall to zero. If not, researcher should be able to put their fingers on what went wrong. What was it? Do participants overlook risks? Do health care and cosmetic service providers continue unsafe procedures?

Decades of prevention research missed the point

Over more than 30 years, foreign-funded medical researchers in Africa recruited hundreds of thousands of men and women into trials to test various ways to protect them from getting HIV. Most such research repeated simple errors.

Not asking to investigate unexplained infections

Trials saw and reported HIV-positive men and women who denied sexual risk. None of the researchers involved publicly  recommended investigations to find how such participants got HIV. Here’s one of many examples:

  • A trial in Mpumalanga, South Africa saw 82 unexplained infections in young women. Among more than 2,000 women aged 13-20 enrolled in 2011-12, 38 who reported never having vaginal or anal sex were HIV-positive.[1] While following and retesting women through 2017, the study saw another 44 new infections in self-reported virgins. The study team considered unexplained infections as evidence of “misreporting on sexual behaviors.”[2,3]

By seeing unexplained infections but not recommending investigations, researchers failed to protect trial participants and other patients. They thereby violated ethical obligations laid out in the World Medical Association’s (WMA) Declaration of Lisbon: “Quality assurance should always be a part of health care. Physicians, in particular, should accept responsibility for being guardians of the quality of medical services.”[4]

Not protecting participants from sexual risks

No HIV prevention trial traced and tested sexual partners of trial participants at the beginning of the trial in order to warn participants if partners were infected. For example:

  • A 2016-19 trial enrolled and followed more than 3,000 women age 18-35 years at 15 sites across South Africa. Although 89% of the women reported a main sex partner at baseline, the study did not trace and test those partners to see if they were infected and thereby a risk for participants, During follow-up the study saw 239 new infections; women got HIV at the rate of 4.3%/year.[5]

A small minority of trials included spouses and other long-term partners and so tested them as well (without having to trace them), but even then, many such studies did not warn participants their spouses were infected. For example:

  • A 1989-97 study in Uganda (part of which was a trial) watched 12 husbands and 22 wives with infected partners get HIV. The study tested and followed adults without telling them their HIV status. An estimated 10% of all adults in the study nevertheless learned their HIV status from a local testing service. Tellingly, researchers reported (page 1088 in reference [6]: “we do not know whether individuals… share their test result with their spouse…  none of the HIV-negative adults in discordant marriages reported using a condom.”

Following participants without first testing partners and warning participants if partners were infected did not protect participants according to best practice. In the Uganda study noted in the above bullet, women with HIV-positive partners got HIV at 70 times the rate for women who had HIV-negative partners (10.5%/year vs 0.15%/year). Not protecting participants violates ethical principles in the World Medical Association’s Declaration of Helsinki noted above.[7]

Why were spouses left at risk? The HIV Prevention Trials Network coordinates a lot  of research in Africa. The Network’s guidelines advise caution not to protect participants too much: “…a very robust prevention package could potentially compromise the ability of a study to detect effects of the experimental modality, which undermines the scientific validity and social value of the research.”[8] 

Not warning partners, not identifying a sexual source

As far as I can see, no HIV prevention trial traced and tested sexual partners of participants who turned up with new HIV infections during the trial. By failing to do so, researchers did not establish a sexual source for new infections. For most trials, testing sex partners is not a big challenge; only small minorities of men and women in Africa report more than one sex partner in the past year (with some variation by country).

Moreover, when a participant shows up with a new HIV infection, not testing partners likely left many at risk. If a partner was HIV-negative (so the participant’s infection came from bloodborne transmission or another partner), the partner should be warned about his or her HIV risk. WHO endorsed this best practice as a “strong recommendation” in 2016 (page xvii in reference [9]): “Voluntary assisted partner notification services should be offered as part of a comprehensive package of testing and care offered to people with HIV.”

References

1. Pettifor A, MacPhail C, Selin A, et al. HPTN 068: a randomized control trial of a conditional cash transfer to reduce HIV infection in young women in South Africa – study design and baseline results. AIDS Behav 2016; 9: 1863-1882. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990514/ (accessed 18 December 2018).

2. Stoner MCD, Nguyen N, Kilburn K, et al. Age-disparate partnerships and incident HIV infection in adolescent girls and young women in rural South Africa: an HPTN 068 analysis. AIDS 2019; 33: 83-91. Abstract available at: https://www.ncbi.nlm.nih.gov/pubmed/30289813 (accessed 10 May 2019)

3. Gisselquist, David and Collery, Simon, Indulging Sexual Fantasies Instead of Protecting Public Health: Not Acting on Evidence Young Women in South Africa Got HIV from Non-Sexual Risks (June 15, 2019). Available at: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3405457 (accessed 10 January 2023.

4. World Medical Association (WMA). Declaration of Lisbon on the Rights of the Patient, 5 December 2022. WMA [internet]. Available at: https://www.wma.net/policies-post/wma-declaration-of-lisbon-on-the-rights-of-the-patient/ (accessed 10 January 2023).

5. Gray GE, Becker L-G, Laher F, et al.  Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120–MF59 in Adults. N Eng J Med 2021; 384: 1089-1100. https://www.nejm.org/doi/pdf/10.1056/NEJMoa2031499?articleTools=true. Supplementary information: https://www.nejm.org/doi/suppl/10.1056/NEJMoa2031499/suppl_file/nejmoa2031499_appendix.pdf   

6. Carpenter LM, Kamali A, Ruberantwari A, et al. Rates of HIV-1 transmission within marriage in rural Uganda in relation to the HIV sero-status of the partners. AIDS 1999; 13: 1083-1089.

7. WMA. Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects, 22 September 2022. WMA [internet]. Available at: https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/ (accessed 10 January 2023).

8. Brown B, Sugarman J. HPTN ethics guideline for research, revised February 2020. HIV Prevention Trials Network [internet]. Available at: https://www.hptn.org/sites/default/files/inline-files/HPTNEthicsGuidanceDocument_2.26.20.pdf (accessed 10 January 2023).

9. WHO. HIV self-testing and partner notification services: supplement to consolidated guidelines and HIV testing services. Geneva: WHO, 2016. Available at: https://apps.who.int/iris/bitstream/handle/10665/251655/9789241549868-eng.pdf (accessed 10 January 2023).

eSwatini: recent survey shows how to stop the country’s HIV epidemic


In December 2022, eSwatini’s Ministry of Health published results from a 2021 HIV survey.[1] Although the report does not say so, it shows how to stop the country’s HIV epidemic.

Most women’s infections not from sex

In 2021, women aged 15-49 years were getting HIV at the rate of 1.45% per year. Considering how many men were infected (18.7%) and how many had suppressed viral loads (86.1%), sex explains less than 0.3% of women getting HIV in a year. Hence, most women’s infections — >1.15% out of 1.45% — likely came from blood exposures during health care or cosmetic services, not sex.

Here’s how 2021 survey data show eSwatini women get HIV from sex at <0.3%/year:

  • From the survey 18.7% of men aged 15 and older were HIV-positive of which 86.1% had suppressed viral loads and were no threat to infect anyone through sex. [1]
  • Hence, only 2.6% (= 13.9% x 18.7%) of men were threats to infect their sex partners (18.7% were HIV-positive, but only 13.9% (= 1-86.1%)  of them had unsuppressed viral loads).
  • HIV-positive men with unsuppressed viral loads could be expected to infect 11% of steady sex partners in a year (this 11%/year rate comes from 5 studies that followed men and women in Africa who did not know they were infected; reference[2] summarizes evidence from 5 studies[3-7]).
  • Hence, if 2.6% of HIV-positive men with unsuppressed HIV had regular sex with HIV-negative women, men could be expected to infect 0.29% of women in a year (= 2.6% x 11%/year).
  • BUT 0.29%/year getting HIV from sex is an overestimate, since many HIV-positive men are celibate during any given year (>10% in a recent survey[8], or have partners who are already HIV-positive[9]; and/or use condoms when they don’t know the HIV status of partners.[8]

Finding and stopping bloodborne transmission

The beginning of the end of eSwatini’s HIV nightmare arrives as soon as people – workers, teachers, farmers, clergy, etc – recognize one or more unexplained HIV infections in their community, and for their own protection demand that government investigates. Investigations test others attending suspected source facilities, find more infected, and find specific facilities and procedures that transmitted HIV. Around the world, such investigations have uncovered local outbreaks with 100s to 1,000s of infections from medical procedures. The biggest was in China during 1990-95, with an estimated 100,000 infected when they sold blood and plasma.[2]

References

1. Ministry of Health, eSwatini. Population-based HIV impact assessment: summary sheet. New York: Columbia University, 2022. Available at: https://phia.icap.columbia.edu/wp-content/uploads/2022/12/53059_14_SHIMS3_Summary-sheet-Web.pdf (accessed 29 December 2022).

2. Gisselquist D. Stopping Bloodborne HIV: investigating unexplained infections. London: Adonis & Abbey, 2021. Available at: https://sites.google.com/site/davidgisselquist/stoppingbloodbornehiv (accessed 29 December 2022).

3. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med 2000; 342: 921-929. Available at: https://pubmed.ncbi.nlm.nih.gov/10738050/ (accessed 30 December 2022).

4. Carpenter LM, Kamali A, Ruberantwari A, et al. Rates of HIV-1 transmission within marriage in rural Uganda in relation to the HIV sero-status of the partners. AIDS 1999; 13: 1083-1089. Abstract only available at: https://pubmed.ncbi.nlm.nih.gov/10397539/ (accessed 30 December 2022).

5. Senkoro KP, Boerma JT, Klokke AH, et al. HIV incidence and HIV-associated mortality in a cohort of factory workers and their spouses in Tanzania, 1991 through 1996. J Acquir Immune Defic Syndr 2000; 23: 194-202. Abstract only available at: https://pubmed.ncbi.nlm.nih.gov/10737435/ (accessed 30 December 2022).

6. Hugonnet S, Mosha F, Todd J, et al. Incidence of HIV infection in stable sexual partnerships: a retrospective cohort study of 1802 couples in Mwanza Region, Tanzania. J Acquir Immune Defic Syndr 2002; 30: 73- 80. Abstract only available at:  https://pubmed.ncbi.nlm.nih.gov/12048366/ (accessed 30 December 2022).

7. Serwadda D, Gray RH, Wawer MJ, et al. The social dynamics of HIV transmission as reflected through discordant couples in rural Uganda. AIDS 1995; 9: 745-750. Abstract only available at: https://pubmed.ncbi.nlm.nih.gov/7546420/ (accessed 30 December 2022).

8. Ministry of Health, Swaziland. Swaziland HIV incidence measurement survey 2 (SHIMS 2) 2016-17. New York: Columbia, 2019. Available at: https://phia.icap.columbia.edu/wp-content/uploads/2020/02/SHIMS2_Final-Report_05.03.2019_forWEB.pdf (accessed 29 December 2022).

9. Central Statistical Office, Swaziland. Swaziland Demographic and Health Survey 2006-07. Calverton (MD): Macro International; 2008. Available at:  https://dhsprogram.com/publications/publication-fr202-dhs-final-reports.cfm (accessed 29 December 2022).

Protect women? Investigate unexplained HIV infections, and shun dangerous interventions


[Note: This blog responds to news that Wits University, South Africa, plans to promote HIV pre-exposure prophylaxis (PrEP) to women through pills, injections and vaginal rings.][1,2]

To protect African women from HIV – to protect yourself, too – pay attention to HIV in women with no sex risks. Women go for a lot of sex-related health care: pregnancy care, child delivery, birth control injections, etc. When skin-piercing procedures in health care and cosmetic services transmit HIV, women are on the front lines.

Ignoring unexplained infections, Africa’s government health agencies operate with the fiction that almost all HIV-positive adults got it from sex. That fiction denies evidence, which says bloodborne transmission is more common than sexual transmission.[3] Many HIV/AIDS experts in and outside Africa who promote the sex-does-it-all fiction know it’s wrong (but lie). Many health staff – along with much of the general public – are not aware it’s fiction. 

Most women avoid sexual exposure to HIV with condoms and tested partners. But if they believe the sex-does- it-all lie, they aren’t alert to avoid unsterilized skin-piercing instruments in health care and cosmetic services. So they get HIV from blood, not sex.

Building on the fiction that sex accounts for most infections, health experts and agencies (WHO, UNAIDS, others) push new medical interventions for women in Africa to use to protect themselves from HIV via sex. Three such interventions deliver antiretroviral medicine for pre-exposure prophylaxis (PrEP) in: daily pills, injections, and vaginal rings.

PrEP pills

In 2015, WHO recommended young HIV-negative African women at high risk for HIV (in communities where ~3% or more get HIV every year) to take PrEP pills daily to prevent HIV infection after exposure.[4] Currently, most PrEP pills deliver two antiretroviral medicines, tenofovir and emtricitabine, or TDF-FTC.

PrEP pills work. If taken daily, they will almost always stop HIV: In a trial among men-who-have-sex-with-men (MSM) reported in 2014, “No infections occurred during periods when drug concentrations were commensurate with use of 4 or more tablets per week.”[5] PrEP stops bloodborne transmission as well: In a trial reported in 2013, PrEP pills reduced new infections among injection drug users in Thailand by almost half.[6]

Table: Selected complaints from women taking PrEP pills in a 2017-20 trial in Africa[7]

Adverse event% of women complaining
Gastrointestinal disorders23%
Abnormal uterine bleeding19%
Headache17%
Upper respiratory tract infection19%
Back pain7%

Nevertheless, in multiple trials in Africa, women taking PrEP pills got HIV as fast as women taking placebo pills (with no medicine).[8] The problem seems to have been that many women believed the lie that almost all HIV comes from risk. Because PrEP gives women diarrhea, headaches, body aches, etc (see Table), many women skipped pills when they had no sex risks. Then they got HIV from unsuspected bloodborne risks.

Cabotegravir injections

To overcome the problem of women not taking PrEP pills, prominent foreign agencies including WHO,[9] USAID,[10] and others urge African governments to offer cabotegravir PrEP injections every eight weeks. Zimbabwe approved cabotegravir PrEP in 2022, and South Africa is expected to do so in early 2023.[1] 

Unlike TDF-FTC from pills, which stays in bodies for days only, the injected cabotegravir stays in blood for months, escaping slowly over time. An injection every eight weeks keeps blood levels high enough to stop most (not all!) new HIV infections. Two recent trials comparing cabotegravir vs. pills found that both stopped HIV, except that pills didn’t work when people didn’t take them:

  • A 2017-20 trial in Africa divided women into two “arms.” Women in one arm got cabotegravir injections every 8 weeks; women in the other got TDF-FTC pills.[7] The study reported 4 new HIV infections with cabotegravir vs. 36 with TDF-FTC. However, (quote from page 1784): “Poor or non-adherence (<2 doses per week) was observed in most TDF-FTC incident [new] infections (35 [98%] of 36).”
  • A similar trial followed MSM in the US and six other countries during 2016-20.[11,12] In this study as well (quote from page 607 in[11]), “…inadequate TDF–FTC adherence among some participants appeared to drive the overall finding of [lower] HIV incidence… in the cabotegravir group…”

The two trials mentioned above reported unpleasant side effects along with serious health threats. In the African trial, women’s complaints with cabotegravir were similar to those with PrEP pills (Table above). In additional, trials reported:

  • Liver damage: In the trial among MSM, more than 2% quit the trial because of “liver-related adverse events.”
  • HIV resistance: Because medicine from injections stays in the blood for a long time, it can mask new infections, allowing HIV to multiply and accumulate resistance mutations. The trial among women in Africa saw 5 cases of resistance; the trial among MSM reported resistance and delays in seeing new infections.

The “sales pitch” for cabotegravir for African women is injections every eight weeks take away women’s day-by-day control over PrEP drugs in their blood. With cabotegravir they can’t stop PrEP on days they don’t have sex risks. Will women accept cabotegravir? Women who are persuaded – somehow – to take it will suffer unpleasant and health-threatening side effects but will be protected from bloodborne as well as sexual transmission. However, any such benefits to some women leave others – men, women, children – exposed to continuing bloodborne transmission in health care and cosmetic services.

Vaginal rings with dapivirine

The European Medicines Agency in 2020 approved dapivirine vaginal rings for women outside the EU.[13] In 2021, WHO recommended rings for women at high risk.[14] Through end-2022, governments of Zimbabwe, South Africa, and several other countries approved the rings.[15]

Current enthusiasm for vaginal rings with dapivirine (an antiretroviral) conflicts with less-than-impressive results from two 2012-15 trials.

  • Ring trial: Women aged 18-45 in South Africa and Uganda got HIV at the rate of 4.1%/year with dapirivine rings and 6.1%/year with placebo rings (without medicine).[16]
  • Aspire trial: Women aged 18-45 years in South Africa, Malawi, Uganda, and Zimbabwe got HIV at the rate of 3.3%/year with dapivirine rings, and 4.5%/year with placebo rings.[17]

Sex risks? In the Ring trial, 98% reported a main sex partner. In the Aspire trial 57% reported using a condom at their last sex act, 41% were married, and 97% reported having the same primary partner for the past 3 months. In both trials, women reported an average of 2 vaginal sex acts per week. With such behavior, half to two-thirds or more of their primary partners would have to be HIV-positive for sex to account for observed new infections, which is absurd (in the Aspire trial, 1% of women knew their primary partner was HIV-positive, 55% knew he was HIV-negative, and 43% did not know[18]). Considering women’s limited sex risks, bloodborne transmission likely accounted for most new infections in both trials.

Did the rings work at all? Comparing dapivirine rings to placebo rings is misleading. Both rings disturb the vagina (inflammation, different microbes), favoring sexual transmission. That seems to have happened in a previous study comparing antiretroviral vaginal gel to a placebo gel – and to placebo daily pills. Women with either gel got HIV faster than women with placebo pills (6.0% with antiretroviral gel, 6.8% with placebo gel, but only 4.6% with placebo pills).[19] Furthermore, the modestly lower rate of new infections in women using dapivirine vs. placebo rings might have had nothing to do with sexual transmission, but might have been due to trace amounts of dapivirine in blood blocking bloodborne transmission.

As demonstrated in the trials, dapivirine rings are disasterouse failures. The trials saw women using them get HIV at 3.3%-4.1%/year. At those rates, 33%-44% of women would be HIV-positive in 10 years. Women who want to avoid HIV should rely on something else.

Conclusion: Protecting women takes a back seat to professional self-interest

Knowing how women get HIV could guide programs to reduce their risks. Trials among women in Africa discussed above (one for cabotegravir, two for vaginal rings) could have looked for risks that infected women. They didn’t. None tested partners after women got HIV. Without testing trials cannot confirm sexual transmission. As for bloodborne risks, none of the trials asked about and reported skin-piercing events in health care and cosmetic services.

Experts directing many other studies among women in Africa display similar lack of curiosity about how women got HIV at high rates. For example:

  • A 2016-19 trial of a candidate HIV vaccine in 15 sites across South Africa reported women aged 18-25 years got HIV at the rate of 4.7%-4.4%/year (the higher rate was in women taking the candidate vaccine).[20]
  • A 2015-18 trial to see the impact of various birth control technologies on women’s HIV risk enrolled women aged 16-35 years in nine sites across South Africa. The overall rate at which women got HIV was 4.5%/year, going as high as 6.8%/year at a site in KwaZulu-Natal.[21]

Neither of these trials – high profile, with lots of resources to ask about anything – tested partners, and neither asked about and reported bloodborne risks. Without evidence, trial reports simply assumed sexual transmission, even though the rates at which women got HIV were too high to be explained by sex.

If protecting women is the goal: (a) governments should investigate unexplained infections to find and stop bloodborne transmission; (b) trials (such as cited here) should look for women’s sex and bloodborne risks; (c) based on what experts learn from (a) and (b), public health programs should warn women about bloodborne risks; and (d) public health programs should stop abusing HIV-positive women by saying almost all HIV comes from sex.

In promoting PrEP pills, injections, and rings for women in Africa, health staff at WHO, European Medicines Agency, USAID, Wits, and other organizations have chosen the self-serving option – protecting their reputations by ignoring unexplained infections that likely came from unsafe health care, and promoting new medical interventions which expand health agencies and incomes even though proposed impacts on HIV sexual transmission are suspect and come with health threats. For sure, special circumstances might warrant these technologies for some people, such as MSM, some prostitutes, and women who want to get pregnant by HIV-positive men with uncontrolled viral loads. But most women in Africa, if warned of all sex and bloodborne risks, can protect themselves without PrEP in any form.

References

1. Gonzalez LL. South Africa to begin piloting injectable PrEP in early 2023. NAM [internet] 7 November 2022. https://www.aidsmap.com/news/nov-2022/south-africa-begin-piloting-injectable-prep-early-2023.

2. Gonzalez LL. South Africa: Pilot projects set to inform rollout of HIV prevention shot. allAfrica [internet] 2022. https://allafrica.com/stories/202211220372.html.

3 Gisselquist D. Recognizing and stopping blood-borne HIV transmission. SSRN [internet] 2 August 2022. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4174723.

4. WHO expands recommendation on oral pre-exposure prophylaxis of HIV infection (PrEP). Geneva: WHO; 2015. https://www.paho.org/sites/default/files/2020-03/cover-eng_46.jpg.

5. Grant RM, et al. An observational study of preexposure prophylaxis uptake, sexual practices, and HIV incidence among men and transgender women who have sex with men. Lancet Infect Dis 2014; 14: 820-829. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107918/pdf/nihms624706.pdf.

6. Choopanya K, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomized, double-blind, placebo controlled phase 3 trial. Lancet 2013, 381: 2083-2090.

7. Delany-Moretlwe S, et al. Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial. Lancet 2022; 399: 1779-89. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077443/pdf/main.pdf.

8. Gisselquist D. Women’s estimated HIV infections from sex in trials of pre-exposure prophylaxis in Africa: Implications for HIV prevention strategies. bioRxiv [internet] 8 June 2017. https://www.biorxiv.org/content/10.1101/146530v1.full.pdf.

9. Guidelines on long-acting injectable cabotegravir for HIV prevention. Geneva: WHO, 28 July 2022. https://www.who.int/publications/i/item/9789240054097.

10. USAID’s Approach to HIV and Optimized Programming. Washington, DC: USAID, 2022. https://www.usaid.gov/sites/default/files/2022-12/HIV_Report_F_single_508.pdf.

11. Landovitz RJ, et al.,Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women. N Eng J Med 2021; 385: 597-608. https://www.hptn.org/sites/default/files/inline-files/nejmoa2101016.pdf.

12. Marzinke MA, et al. Characterization of HIV infection in cisgender men and transgender women who have sex with men receiving injectable cabotegravir for HIV prevention: HPTN 083. J Infect Dis 2021; 224: 1581-92. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599849/.

13. EMA. Dapivirine Vaginal Ring 25 mg: opinion on medicine for use outside EU (dapivirine). EMA [internet] 24 July 2020. Available at: https://www.ema.europa.eu/en/opinion-medicine-use-outside-EU/human/dapivirine-vaginal-ring-25-mg  (accessed 16 December 2022).

14. WHO recommends the dapivirine vaginal ring as a new choice for HIV prevention for women at substantial risk of HIV infection. Geneva: WHO, 2021. https://www.who.int/news/item/26-01-2021-who-recommends-the-dapivirine-vaginal-ring-as-a-new-choice-for-hiv-prevention-for-women-at-substantial-risk-of-hiv-infection.

15. International Partnership for Microbicides (IPM). Dapivirine ring. IPM [internet]. https://www.ipmglobal.org/our-work/our-products/dapivirine-ring.

16. Nel A, et al. Safety and efficacy of a Dapivirine vaginal ring for HIV prevention in women. NEJM 2016; 375: 2133-43. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1602046.

17. Baeten JM, et al. Use of a vaginal ring containing dapivirine for HIV prevention in women. N Eng J Med 2016; 375: 2121-32. https://www.nejm.org/doi/full/10.1056/nejmoa1506110.

18. Palanee-Phillips T, et al. Characteristics of women enrolled into a randomized clinical trial of dapivirine vaginal ring for HIV-1 prevention. PLOS ONE 2015; 10: e0128857. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489588/.

19. Marrazzo JM, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Eng J Med 2015; 372: 509- 518, with supplementary materials. https://www.nejm.org/doi/full/10.1056/nejmoa1402269.

20. Gray GE, et al.  Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120–MF59 in Adults. N Eng J Med 2021; 384: 1089-1100. https://www.nejm.org/doi/pdf/10.1056/NEJMoa2031499?articleTools=true.

21. Palanee-Phillips T, et al. High HIV incidence among young women in South Africa: Data from a large prospective study.  PLoS One 2022; 17: e0269317. https://pubmed.ncbi.nlm.nih.gov/35657948.