Bloodborne HIV: Don't Get Stuck!

More than a dozen studies over decades found that women who used Depo for birth control were more likely to get HIV than women who didn’t use it. Despite that evidence, governments of the US and Sweden, the Bill and Melinda Gates Foundation, and the UN Population Fund arranged and funded the ECHO trial (Evidence for Contraceptive Options and HIV Outcomes).[1]

The ECHO 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 that Depo use increased women’s risk to get HIV by 40-50%.[2,3,4] Hence, 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.”[5]

The principle here is “equipoise”: research can be justified in situations where so far we don’t know the answer. But, in this case, we already know the answer. Giving women Depo to watch them get HIV is like asking women to cross streets with their eyes closed to see if they are more likely to get hit by cars vs. women who keep their eyes open.

As for  intrauterine devices and implants (the other two birth control methods in the study), there is not enough information to say what if any impact they have on women’s HIV risk. Similarly, no one can say if monthly injections of NET-EN (norethisterone enanthate) effect women’s HIV risk. The ECHO trial could have been both ethical AND useful if it had tested those methods against a safe option.  And there is a safe option: According to a lot of research, both before and after the ECHO trial began, pills do not increase women’s risk for HIV.[3,6] Hence, the ECHO trial could have tested various birth control methods (but NOT Depo) against pills. Such a trial would satisfy The Declaration of Helsinki ethical guidelines[5]: “The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best proven intervention(s)..”

As it turned out, and as could have been expected, a lot of women got HIV during the ECHO trial — almost 4% per year for all methods. 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.

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 and committees at WHO and Columbia University approved it as ethical.[1]

ECHO trial results have been widely misinterpreted. A report of the trial in The New York Times, for example, said the results show Depo-Provera “does not raise HIV risk.” Because the trial did not compare Depo-Provera to pills, it does not support that statement.[7] Just nonsense!

Like many other studies in Africa, the study withholds collected information that is relevant to assess sexual and non-sexual risks. Encouragingly, the study tested partners for HIV (pp 305-6 in [1]), but the study does not say how many partners tested HIV-positive or how much having an HIV-positive partner increased a woman’s HIV risk. Huh, isn’t that relevant to understand what happened?

The study does not report if women who got HIV during follow-up intervals reported any sex acts during those intervals — with HIV-positive partners or with anyone else. Withholding relevant information also violates the Declaration of Helsinki (article 36: “Researchers have a duty to make publicly available the results of their research on human subjects and are accountable for the completeness and accuracy of their reports…”).[5]

Aside from not reporting all relevant collected information, by all accounts the study did not collect other relevant information. Like most other foreign-funded HIV research in Africa, the study ignored non-sexual risks.

How to stop these outrages? Appealing to courts may get better results than waiting for health care professionals to change. Recently, a US court allowed Guatemalans harmed during medical research to sue private US institutions in US courts.[8] Does this mean that any woman in the ECHO trial randomized to Depo-Provera who got HIV during the trial could sue private US institutions involved in the trial in US courts?

References

1. 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; published online June 13. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31288-7/fulltext; supplementary appendix available at: http://echo-consortium.com/wp-content/uploads/2019/06/ECHO-primary-HIV-results-appendix-Lancet-online-first-June-2019.pdf (accessed 24 May 2022)

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. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526270/ (accessed 24 May 2022).

3. Morrison CS, Chen PL, Kwok C, et al. Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis. PLoS Med 2015; 12: e1001778. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303292/ (accessed 26 July 2019).

4. 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. Abstract available at: https://www.ncbi.nlm.nih.gov/pubmed/?term=brind+condly+mosher (accessed 5 March 2018). More results from this review are at: Depo-Provera and HIV. PRI, no date. Available at: https://www.pop.org/depo-provera-and-hiv/ (accessed 6 March 2018).

5. World Medical Association (WMA). WMA Declaration of Helsinki – ethical principles for medical research involving human subject, amended October 2013. Ferney-Voltaire, France: WMA, 2013. Available at: https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/ (accessed 24 May 2022).

6. Polis CB, Curtis KM, Hannaford PC, et al. An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in women. AIDS 2016; 30: 2665–83. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106090/ (accessed 26 July 2019).

7. McNeil DG. Depo-Provera, an injectable contraceptive, does not raise HIV risk. New York Times 13 June 2019. Available at: https://www.nytimes.com/2019/06/13/health/depo-provera-hiv-africa.html (accessed 27 July 2019).

8. Stempel J. Johns Hopkins, Bristol-Myers to face $1 billion syphilis infections suit. Reuters 4 January 2019. Available at: https://www.reuters.com/article/us-maryland-lawsuit-infections/johns-hopkins-bristol-myers-must-face-1-billion-syphilis-infections-suit-idUSKCN1OY1N3 (accessed 26 July 2019).