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. 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.”
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.
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 : “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.
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.”
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 ): “Voluntary assisted partner notification services should be offered as part of a comprehensive package of testing and care offered to people with HIV.”
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).