Blame the research design for the failure of the HIV study

In the last decade, the medical community has made great strides in methods of preventing HIV. It’s a promising landscape, with studies showing the effectiveness of antiretrovirals (ARVs) as the basis for pills, topical gels, and barrier methods that men and women can use to protect themselves from HIV.

Unfortunately, a recent study published in the prestigious New England Journal of Medicine (NEJM) represents a step backwards. Known as VOICE, or vaginal and oral interventions to control the epidemic, the study showed no preventive results for women in southern Africa using pre-exposure prophylaxis (PrEP) pills made with ARV or topical microbicidal gel.

This is a particularly troubling failure because previous studies have shown that these ARV-based methods work. Most of the women who took part in the VOICE study did not use the tablets or gel, but those who did were protected. In other words, the study failed not because the products didn’t work but because they weren’t used.

The scientific community suspects that the VOICE study has presented disappointing results since 2011, when the research – involving more than 5,000 women and costing $ 94 million – was halted for vain. The main explanation of the NEJM authors for the failure is the deception and lack of conformity of the participants.

But when a study fails, we must be careful not to imply that the subjects are at fault. Rather, my analysis of the study suggests that the research design was to blame. The stake of this research is more social and behavioral than medical; to be successful, we need to better understand which routines and methods work best for women under stressful everyday conditions. If the proposed methods are not used, researchers must rethink their approach or women at risk will continue to be infected with HIV and the epidemic will escalate.

In any clinical trial, it is the responsibility of the researchers to build trust. Without long-term preparation, any community will be wary of new interventions. Particularly in South Africa, where many VOICE participants have been recruited, researchers face significant cultural challenges, including more than 40 years of apartheid and a decade of Ministry of Health-backed AIDS denial.

Despite this history, a campaign of grassroots and sustained global treatment action, which included the efforts of Nelson Mandela in his later years, led to a change in government policy and the provision of ARV treatment by the state health system. When the program was launched, millions of South Africans consistently adhered to the treatment. Many lives have been saved and others protected from infection.

Any new research requires community involvement and a rigorous evaluation of practices. VOICE researchers could have learned lessons from a successful microbicide trial, CAPRISA 004, led by the Center for the AIDS Program of Research in South Africa. After conducting interviews, the researchers decided to ask women to use the microbicidal gel only before and after sex, rather than daily. This took into account that many of their partners were migrant workers who were absent for long periods of time and that the women might not stick to an unnecessary daily routine, knowing that they were unlikely to have any problems. sexual relations. The researchers set up an interactive feedback system: the women were asked to return the microbicidal gel applicators (which were tested as the study progressed to detect if they had been used appropriately. ) and meet motivational advisers. In 2010, the CAPRISA trial found that many women used the microbicide the day they had sex and that it was protective.

Rather than follow this precedent, the VOICE researchers instructed its participants to use the microbicide on a daily basis. The trial failed because the women did not use the products as directed. The NEJM article focuses on the fact that the women did not always disclose that they had not taken the pills or used the gel and handed over pill bottles and applicators that appeared to have been used – even though subsequent blood tests showed no trace of the study drug. . With permanent biomarkers and more effective feedback mechanisms, these issues may have surfaced and been resolved sooner.

The VOICE study appeared to lack sufficient community engagement. CAPRISA 004 focused on women in Durban (just like VOICE) and Vulindlela, a rural area outside of Durban. First securing the support of local Zulu chiefs, CAPRISA developed extensive community engagements in Vulindlela. Doctors attended local council events and the clinic provided AIDS treatment. It is significant that the results of CAPRISA 004 were much better in Vulindlela than they were in Durban. Women in rural areas have historically been more constrained by patriarchal relationships, more wary of drugs labeled toxic by traditional leaders, and therefore less likely to adhere to preventive measures than women in urban areas. Data suggests that substantial long-term community engagement in Vulindlela has boosted women’s cooperation. Rather than building on these important successes, VOICE apparently did not sufficiently consider the social situations of women in its study.

Bottom-up search design can improve results, but it takes time, costs money, and disrupts accepted hierarchies. Since funders and donors may not recognize the need to incorporate the costs of community engagement, studies are more likely to focus on pharmaceutical methods than on a large investment in local engagement. But as we have learned from decades of research on AIDS and recently with Ebola, without continued community involvement, it is not possible to effectively fight an epidemic.

The high incidence of HIV seen in the VOICE study reminds us that we desperately need methods that women can more easily apply in difficult situations, especially those most at risk in southern Africa: women ages 15-22. years. There are at least two promising products on the horizon – one a monthly ring, the other an injection given four times a year – that could become additional and vital tools in the fight against this ongoing crisis.

Meanwhile, PrEP is not a panacea. Not only are there side effects, but people should use it appropriately as well. But making PrEP available wherever women are at risk – not just for women in the United States – is a critical next step nonetheless. Most importantly, to reduce the incidence of HIV infection globally, we need to work with women and men at the community level to promote trust and identify the best ways to use the effective methods we already have. .