[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. 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.
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. 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.” 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.
Table: Selected complaints from women taking PrEP pills in a 2017-20 trial in Africa
% of women complaining
Abnormal uterine bleeding
Upper respiratory tract infection
Nevertheless, in multiple trials in Africa, women taking PrEP pills got HIV as fast as women taking placebo pills (with no medicine). 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.
To overcome the problem of women not taking PrEP pills, prominent foreign agencies including WHO, USAID, 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.
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. 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), “…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 two 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. In 2021, WHO recommended rings for women at high risk. Through end-2022, governments of Zimbabwe, South Africa, and several other countries approved the rings.
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).
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.
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). 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). 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).
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.
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.
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.
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/.