Annex 2: Unethical HIV Research in Africa

The HIV-related research projects discussed here violate common sense ideas about what is right. They also violate the World Medical Association’s Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects, articles 4 and 7: “It is the duty of the physician to promote and safeguard the health, well-being, and rights of patients, including those who are involved in medical research”; and “Medical research is subject to ethical standards that promote and ensure respect for all human subjects and protect their health and rights.”[1]

Many organizations that have funded or approved unethical research in sub-Saharan Africa have also influenced responses to HIV epidemics in Africa. The double standard they have demonstrated with respect to research parallels a similar double standard in their responses to HIV from health care in Africa (Chapter 3). Double standards apply to other countries as well. Where governments allow, foreigners have all too often paid for unethical research and unsafe health care that would not be allowed in their home countries. The organizations named here do a lot of good much of the time, but not always.

Sections below discuss selected studies with ethical problems, beginning with the most recent. In these studies, researchers: gave women a drug known to increase their HIV risk; followed people not aware they were HIV-positive to watch them infect spouses and/or children and to watch them get sick and die of AIDS; followed vulnerable women without addressing their priority, which was to find out how they got HIV so other women could protect themselves; and did not investigate evidence a study clinic had infected participants.

The last section lists foreign organizations that funded or approved each project. This annex is by no means an exhaustive account of unethical foreign-funded HIV-related research in Africa.

2015-18: Giving women a drug that increases their HIV risk

Depo-Provera (briefly: Depo) is a drug similar to the hormone progesterone. Women who use it for birth control get Depo injections every three months. In the early 1990s, researchers found evidence that Depo use increased women’s risk to get HIV. That finding was subsequently repeated in many later studies. Importantly, women have safe options: many studies have found that birth control pills do not increase women’s risk to get HIV.[2,3]

Evidence that Depo use increased women’s risk for HIV is important for women in Africa. In most countries where foreign aid is not a factor, the percentage of women using Depo is low or nil.[4] However, across much of Africa, large percentages of women use Depo. For example, as of latest information from 2013-2018, more than 20% of married or partnered women in South Africa, Zambia, Namibia, and Malawi used hormone injections for birth control (mostly Depo, but also some NET-EN,[4] which seems to have less or no impact on women’s HIV risk).

Despite mounting evidence Depo use increases women’s HIV risk, influential organizations including USAID and the Bill and Melinda Gates Foundation continued to promote Depo in Africa. To challenge the evidence, USAID, the Bill and Melinda Gate Foundation, and others (Table A2.2) arranged and funded the ECHO trial (Evidence for Contraceptive Options and HIV Outcomes).[5] The trial randomly assigned more than 7,000 HIV-negative women in eSwatini, Kenya, South Africa, and Zambia to one of three birth control methods: Depo, an intrauterine device, or a hormone implant. During 2015-18, the ECHO trial followed and retested women to see who got HIV.

The trial was unethical: Before the ECHO trial began to enroll women in December 2015, three reviews of accumulated evidence (from 10-18 studies published during 1993-2014) had estimated Depo use increased women’s risk to get HIV by 40% to 50%.[2,3,6,7] Assigning research participants to Depo violated the Declaration of Helsinki’s admonition to “promote and safeguard the health, well-being and rights of patients, including those who are involved in medical research.”[1]

As for intrauterine devices and implants, the other two contraceptives in the study, there was too little information to say what if any impact they have on women’s HIV risk; testing Depo against those methods was meaningless. Hence, the trial was not only unethical, it was pointless. No matter what the trial found about women getting HIV with one or another method, results could not say Depo was safe. As it turned out, HIV risk among all women was high, with almost 4% getting HIV each year, Women taking Depo got HIV a bit faster, at 4.2% per year. Such high rates likely include a lot of infections from bloodborne risks (see Chapter 6).

The ECHO trial had no problem finding people willing to do the dirty work – to implement unethical research – and no problem getting ethical approval. More than 750 people collaborated in ECHO research[5] and multiple committees approved it (see last section in this annex).

2012-16: Following women at high risk to study very new infections

Scientists working on HIV vaccines and cures would like to know what happens during very early HIV infections, in the first several weeks and months after the virus enters the body.[8] To study very early infections, researchers recruited women aged 18-23 years from the Umlazi Township in KwaZulu-Natal, South Africa, where the percentage of women HIV-positive had been seen to “rise from less than 1% at age 15 to 66% at age 23.”[9] To see new HIV infections, this location was a good choice. Women in the study got HIV at the rate of 8.2% per year.

Because women in the community were at such high risk to get HIV, they were a vulnerable group, for which the Declaration of Helsinki mandates special protection (article 20): “Medical research with a vulnerable group is only justified if the research is responsive to the health needs or priorities of this group…”[1] Given the very high rate at which young women in the community were getting HIV, the priority was to identify how women in the study got HIV, so women in the community could be warned about what risks to avoid. The study was unethical, ignoring women’s priority while taking advantage of their vulnerability (high risk for HIV) to study new infections. (If the study had addressed the priority – how women got HIV – but had also collected information from new infections that might help to develop vaccines and cures, that was arguably ethical.)

The study tested women’s blood for HIV virus twice per week. Because virus generally shows up in blood 1-2 weeks after the event that caused the infection, the study was ideally designed to identify specific events that led to infections. The study saw 42 new infections. Most women had one partner, so testing partners at the beginning of the study and new partners during the study was one way not only to protect women in the study but also to see how they got HIV. The study says nothing about tracing and testing partners to see if they were the sources of women’s new infections, and has not reported women’s sexual events in the 1-3 weeks before virus appeared in their blood.

Considering the very high rate at which women were getting HIV, the study team should have considered blood exposures as well. Did women with new infections have an injection, manicure, or other skin-piercing event 1-3 weeks ago? Aside from injections for birth control, the study does not report anything about skin-piercing events, and there is no indication it asked.

An early report from the study says women who reported injections for birth control (mostly Depo, but also some NET-EN) got HIV at the rate of 12% per year compared to 3.7% for women who reported not using any long-term birth control; “behavioural differences... could not explain this increased risk.”[10] Considering that Depo use increases women’s HIV risk by 40%-50% only, most new infections in women getting injections for birth control likely came from contaminated injections. But the study does not say if women reported birth control injections 1-3 weeks before showing up with a new infection, or if they reported sex with an HIV-positive man or with any man during that time. That would help to determine if the injections infected women or if Depo use increased their susceptibility to sexual transmission.

Even if women had not been vulnerable, researchers had “a duty” according to article 6 in the Declaration of Helsinki[1] “to make publicly available the results of their research on human subjects and are accountable for the completeness and accuracy of their reports.” Not identifying the events that infected women was not only unethical, it was also bad science. Bodies respond differently if HIV enters through a skin-piercing event or through sex. Assuming all women got HIV from sex could lead to a lot of confusion if many or most of their infections came from blood risks.

1989-2007: Following couples unaware one is infected to watch one infect the other

Beginning in 1989 and continuing at least to 2003-7, foreign-funded research projects in Africa tested, followed, and re-tested thousands of adults without routinely telling them the results of their HIV tests. In many such studies, the populations followed included couples in which only one partner was infected. When researchers know someone is at risk to get HIV from an infected spouse but do not tell them, researchers are not doing their duty to protect participants’ health. (To be ethical, projects can refuse to enroll people who do not want to know their HIV test results and are unwilling to tell their spouse.)

At least five such projects have reported the numbers of men and women at risk from HIV-positive partners, and how many at-risk spouses got HIV. These five studies (Table A2.1) collectively reported 145 new infections in 723 exposed spouses. Combining data from the five studies, at-risk wives got HIV at the rate of 11.1% per year, while at- risk husbands got HIV at the rate of 8.6% per year. (Some new infections in at-risk partners likely came from sources other than their HIV-positive partners; the same studies reported adults with HIV-negative spouses getting HIV at rates as high as 0.9% per year[16]).

The percentage of HIV-positive partners knowing they were infected may have exceeded 50% in Rakai, 1994-98, but was much lower in other studies. Based on what has been reported (see below), it seems likely more than three-fifths of HIV-positive partners in the five studies combined did not know they were infected, and even more HIV-negative partners did not know they were at risk. Condom use was low in all studies. Here’s what the five studies say about who knew what and how many used condoms.

Uganda, Rakai, 1994-98[11]

The study does not say how many infected and at-risk partners learned their HIV status. However, another study with more than 40% of the same couples reported[17]: “56% of HIV-1-positive partners in these discordant relationships had requested and received HIV counseling, and 25% stated that they had informed their spouses”; but even so, 92.5% “had never used condoms” and only 1.2% “reported consistent use.”

Uganda, Masaka, 1989-97[12]

Less than 10% of participants received their test results, “and we do not know whether individuals who come for counseling share their test result with their spouse… none of the HIV-negative adults in discordant marriages reported using a condom.”

Tanzania, urban Mwanza, 1991-96[13]

“…HIV test results were only provided if the study participants requested it… [L]ess than 10% of the study participants made use of these services.” Among 88 couples with an HIV-positive partner, “No condoms were used by any of the couples.”

Tanzania, rural Mwanza, 1991-94[14]

Research participants “were only informed of their HIV status if they accessed a parallel voluntary counseling and testing service. Only a small number of participants pursued this service. At follow-up, only 5% of men reported having ever used a condom.”

Uganda, Rakai, 1990-91[15]

"Among the serodiscordant couples, only 10 men (12.7%) and six women (7.2%) requested both counseling and their HIV test results during 1990-91.” In couples where one partner was infected, 2.1% of HIV-negative women and 17% of HIV-negative men reported condom use.

Uganda, Rakai, 2003-7[18]

Similar unethical practices continued into the twenty-first century. To find out what effect circumcising HIV-positive men would have on how fast they infected their sex partners, a study in Rakai, Uganda, during 2003-7 recruited intact (uncircumcised) men who were HIV-positive and their HIV-negative wives. After circumcising some men and not others, the study followed wives to see who got HIV (this study was linked to the continuing Rakai community study; see first and last entries in Table A2.1).

Six of the 155 HIV-positive men in the study refused to get the results of their HIV test when they entered the study. The study does not say how many men who knew they were infected warned their wives; however, in another study with many of the same couples, more than 80% of HIV-positive men told their wives.[19] Relative to what researchers had done in previous studies, what was done in this study – following a small number of wives unaware their husbands were infected – could be considered a minor ethical violation. But it was also so unnecessary that it exposes careless disregard for ethical principles. The percentages of men who would not hear their HIV status and who knew but would not tell their wives were so small that even without them the trial almost surely could have recruited enough couples for the study.

2002-6: Not looking to see if men got HIV from research clinics

Researchers in Kenya during 2002-6 recruited men willing to be circumcised, then on a random basis assigned half to an intervention group to be circumcised first and half to a control group to remain intact (uncircumcised) until the end of the study. The study followed and retested men for up to two years.[20]

The study found four men with new HIV infections one month after circumcision. Three of the four reported no sexual activity during the month. When such unexplained infections are recognized during medical research, they are “unanticipated problems” or “adverse events.” The Declaration of Helsinki admonishes researchers to report adverse events to oversight committees (article 23).[1] The study’s account of adverse events does not include these HIV infections in men a month after circumcisions. There is no indication the study team or committees monitoring the research recognized these unexplained infections as unanticipated problems to be reported and investigated.[21]

To see if the research clinic infected any of the four men, an investigation could have checked when each man was circumcised, tested others attending the clinic on the same days, sequenced HIV from the four men and from anyone else found HIV-positive, and then looked for similar sequences.

1990-2004: Following and not treating adults unaware they are HIV-positive to watch them get sick and die of AIDS

In 1989, researchers in Uganda began a long-term study in 15 villages (later expanded to 25 villages) in Masaka District.[22] During repeat surveys, researchers tested adults for HIV, but did not tell them if they were infected. The study encouraged them to go for HIV tests elsewhere if they wanted to know. Before 2004, “only approximately 10% of the population knew their HIV status.”[22]

Beginning in 1990, the Masaka study invited adults found to be HIV- positive along with spouses and some other HIV-negative people into a Natural History Cohort. The study did not tell Cohort members if they were infected. Because the Cohort included HIV-negative adults, no one either in or outside the Cohort would know who was infected.[23]

The study asked people in the Cohort to visit a study clinic every three months for a physical exam. To allow “unbiased reporting of symptoms and signs,” the project did not tell staff at the study clinic who was infected.[24] Clinic staff treated Cohort members for “conditions diagnosed using basic laboratory facilities and standard drugs from the WHO essential drug list, which should be available in any health post throughout Africa.”[25]

Masaka researchers used the Natural History Cohort to study “survival times, disease progression, and AIDS-defining disorders” in untreated Africans.[24] As late as 2000, median survival time with AIDS for Cohort members was 9.2 months, “similar to the average of 10 months reported in industrialized countries early in the HIV epidemic.”[25] For HIV-positive Cohort participants, “[p]rimary prophylactic therapy [to prevent tuberculosis and other opportunistic infections that come with HIV] and antiretroviral regimens have been available since 2004.”[26]

Masaka’s Natural History Cohort is similar to the Tuskegee Study of Untreated Syphilis in the Negro Male, a widely reviled blight on the US medical community. In the Tuskegee Study, researchers followed African-American men with syphilis from 1932 to 1972, without treating them. Researchers reported results openly in medical journals. In 1964, for example: “The syphilitic group continues to have higher mortality and morbidity than the uninfected controls, with the cardiovascular system most often involved.”[27] The US Public Health Service stopped the study in 1972, but only after newspapers brought it to the attention of the non-medical US public. In the Tuskegee Study, doctors followed men with tertiary syphilis, who were not at risk to infect others, whereas in Masaka and elsewhere in Africa researchers not only watched people who did not know they had HIV sicken and die, but also watched them infect spouses and children.

1997-2000: Watching mothers unaware they were HIV-positive infect breastfeeding babies

During 1997–2000, the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) study enrolled 14,110 mother-baby pairs within four days after delivery. The study then followed mothers and babies for up to two years, retesting to detect new HIV infections.[28]

Among the 14,110 mothers, 4,495 (32%) were HIV-positive at delivery. “Mothers could learn their [HIV test] results at any time during the study..., but they were not required to do so.”[29] Only 7.2% of mothers asked for their HIV test results by three months after delivery. HIV-positive mothers were less likely to ask. Through the end of the project, only 15.5% of all infected and uninfected mothers heard the results of their tests.[29]

If mothers learned they were HIV-positive, the study advised them to breastfeed for six months, then stop.[29] But if mothers did not know, the study did not tell them their child was at risk. Most HIV-positive mothers continued to breastfeed: 97% were breastfeeding at six months, 92% at 12 months, 66% at 18 months, and 19% at two years.[28] From ages 6-18 months, 121 breastfeeding babies of women who were HIV-positive at delivery got HIV.[30]

After six months, shifting babies to formula was a viable option, and no doubt many parents would have done so if they knew their babies were at risk. The families in this study lived in Harare, the capital of one of the richest countries in Africa.

What to make of this?

Rich country governments and other foreign organizations funded the projects discussed in this chapter, and institutional review boards said they were ethical (Table A2.2). Despite common sense, the Declaration of Helsinki, and other guidelines for medical research, unethical research has been all too common in Africa.

Abbreviations: BASF: Badische Anilin und Soda Fabrik (German chemical company); BMGF: Bill and Melinda Gates Foundation; DfID: UK Department for International Development; IAVI: International AIDS Vaccine Initiative; JHU: Johns Hopkins University; MRC: UK Medical Research Council; LSHTM: London School of Hygiene and Tropical Medicine; NIH: US National Institutes of Health; ODA: UK Overseas Development Administration; PEPFAR: US President’s Emergency Fund for AIDS Relief; U: university; UN: United Nations; USAID: United States Agency for International Development; WHO: World Health Organization. Sources: See references in the second column in each row.


1. World Medical Association (WMA). WMA Declaration of Helsinki – ethical principles for medical research involving human subject, amended October 2013. Ferney-Voltaire, France: WMA, 2013.

2. Ralph LR, McCoy SI, Shiu K, Padian N. Hormonal contraception use and women’s risk of HIV acquisition: a meta-analysis of observational studies. Lancet Infect Dis 2015; 15: 181-89

3. Morrison CS. Chen P-L. Kwok C, et al. Hormonal contraception and the risk of HIV acquisition: an individual participant meta-analysis. PLoS Med 2015; 12: e1001778.

4. UN, Department of Economic and Social Affairs, Population Division. World Contraceptive Use 2020. POP/DB/CP/Rev2020. New York: UN, 2020.

5. Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial Consortium. HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial. Lancet 2019; 394: 303-313.

6. Brind J, Condly SJ, Mosher SW, et al. Risk of HIV infection in depo-medroxyprogesterone acetate (DMPA) users: a systematic review and meta-analysis. Issues in Law and Medicine 2015; 30: 129-138.

7. Depo-Provera and HIV. Population Research Institute [internet], 1 January 2019. Available at: hiv/ (accessed 6 March 2018).

8. Dong KL, Moodley A, Kwon DS, et al. Detection and treatment of Fiebig stage 1 HIV-1 infection in young at-risk women in South Africa: a prospective cohort study. Lancet HIV 2018; 5: e35-e44.

9. Fresh. Ragon Institute of MHG, MIT and Harvard [internet], 2020. Available at; 0FRESH%20study%20(Females%20Rising,they%20are%20infected%2 0with%20HIV (accessed 7 July 2020).

10. Byrne EH, Anahtar MN, Coneh KE, et al. Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in South African women: a prospective cohort study. Lancet Infect Dis 2016; 16: 441-448.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. Wawer MJ, Sewankambo NK, Serwadda D, et al. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomized controlled trial. Lancet 1999; 353: 525-535.

17. Gray RH, Wawer MJ, Brookmeyer R, et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1 discordant couples in Rakai, Uganda. Lancet 2001; 357: 1149-1153.

18. Wawer MJ, Makumbi F, Kigozi G, et al. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomized controlled trial. Lancet 2009; 374: 229-237.

19. Kairania RM, Gray RH, Kiwanuka N, et al. Disclosure of HIV results among discordant couples in Rakai, - Uganda: A facilitated couple counselling approach. AIDS Care 2010; 22: 1041-1051.

20. Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet 2007; 369: 643-656.

21. Gisselquist D. HIV infections as unanticipated problems during medical research in Africa. Account Research 2009; 16: 199-217.

22. Biraro S, Morison LA, Nakiyingi-Miiro J, et al. The role of vertical transmission and health care-related factors in HIV infection of children: a community study in rural Uganda. J Acquir Immune Defic Syndr 2007; 44: 222-228.

23. Morgan D, Malamba SS, Maude GH, et al. An HIV-1 natural history cohort and survival times in rural Uganda. AIDS 1997; 11: 633-640.

24. Morgan D, Maude GH, Malamba SS, et al. HIV-1 disease progression and AIDS-defining disorders in rural Uganda. Lancet 1997; 350: 245- 250.

25. Morgan D, Mahe C, Mayanja B, et al. HIV-1 infection in rural Africa: is there a difference in median time to AIDS and survival compared with that in industrialized countries? AIDS 2002;16: 597-603.

26. Whitworth JA, Birao S, Shafer LA, et al. HIV incidence and recent injections among adults in rural southwestern Uganda. AIDS 2007; 21: 1056-1058.

27. Rockwell DH, Moore MB. The Tuskegee study of untreated syphilis. Arch Int Med 1964; 114: 792–798.

28. Humphrey JH, Iliff PJ, Marinda ET, et al. Effects of a single large dose of vitamin A, given during the postpartum period to HIV-positive women and their infants, on child HIV infection, HIV-free survival, and mortality. J Infect Dis 2006; 193: 860–871.

29. Piwoz EG, Iliff PJ, Tavengwa N, et al. An education and counseling program for preventing breast-feeding-associated HIV transmission in Zimbabwe: design and impact on maternal knowledge and behavior. J Nutr 2005; 135: 950-955.

30 Iliff PJ, Piwoz EG, Tavengwa NV, et al. Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV- free survival. AIDS 2005; 19: 699-708.