The first results of the NAMSAL study, carried out by Swiss, French and Cameroonian teams, have allowed the WHO to revise its AIDS treatment recommendations to better adapt them to more diverse contexts.
Until very recently, the World Health Organization (WHO) recommended two drugs, dolutegravir and efavirenz, for the treatment of HIV infection. However, these two treatments had never been compared under the conditions typically found in countries heavily affected by HIV. A joint study by the University of Geneva (UNIGE) and Geneva University Hospitals (HUG) in Switzerland, the French Research Institute for Development (IRD), and the Central Hospital of Yaoundé in Cameroon, involving 613 patients from various Cameroonian hospitals, the NAMSAL study now eliminates this ambiguity. While both drugs reduce viral load in patients equally, the risk of drug-induced resistance is significantly lower with dolutegravir—a crucial benefit for both public and individual health. These results, published in the New England Journal of Medicine , provided the WHO with its first robust data on this issue. They also emphasize the need to conduct high-quality studies among affected populations, rather than only in patients living in high-income countries, despite the operational complexities of such studies.
Many antiretroviral drugs are available to reduce the HIV viral load (the amount of virus per ml of blood) to an undetectable level. Among the frequently used treatments are efavirenz, which has been available since 1998, and the more recent dolutegravir, introduced in 2013. “While both drugs are well-known, they had never been compared against each other in low-income countries,” says Professor Alexandra Calmy, Vice Dean of the UNIGE Faculty of Medicine in charge of international and humanitarian medicine and head of the HUG HIV/AIDS Unit, who participated in this work. “Therefore, we decided to do so, with the support of ANRS and UNITAID, to base international recommendations on solid evidence.”
A double-blind study
The NAMSAL study (New Antiretroviral and Monitoring Strategies in HIV-Infected Adults in Low-Income Countries) was conducted in Cameroon between July 2016 and October 2018. 613 treatment-naïve people with HIV were randomly assigned to one of two recommended therapies: a daily dose of dolutegravir or a 400 mg dose of efavirenz (a lighter dose than the usual 600 mg dose to reduce adverse reactions), in combination with two other molecules (triple therapy). While the results in terms of viral load after 48 months of treatment are similar between the two groups (approximately three-quarters of patients have seen their viral load fall to an undetectable level), the difference lies in viral resistance for those patients for whom the treatment has not worked as desired.
Take into account the specificities of the populations.
Furthermore, the results of the NAMSAL study show that the effect of both drugs on viral load is less than expected. “Clinical trials conducted for marketing authorization take place in Western patients, the vast majority of whom are men, who also benefit from early detection and good overall health,” explains Dr. Charles Kouanfack of Yaoundé Central Hospital and the first author of this study. “Our patients are very different: two-thirds of them are women who undergo late screening and therefore have a very high initial viral load and often receive little medical follow-up. Treatments take longer to become effective.”
Essential scientific data for the WHO
These results illustrate the importance of such studies in developing international recommendations. “We must have data that are representative of the populations receiving treatment in all their diversity and not select the people included in studies according to overly strict criteria,” says Alexandra Calmy, who is also a WHO expert in the field of HIV/AIDS, as is Professor Delaporte. “I would also like to emphasize the importance of not excluding women from clinical trials, especially when they constitute the majority of patients.” Without this data, the WHO could not recommend one drug over another. Today, the UN agency clearly recommends dolutegravir for the reasons detailed in the study. The update to its recommendations, made in August 2019 following the publication of this work,
This work also illustrates Geneva's expertise in this field, as well as the emphasis placed by UNIGE and HUG on global health. Indeed, both Geneva institutions have mechanisms to encourage research and education in low-income countries and frequently participate in the work of international and humanitarian organizations based in Geneva.
September 24, 2019
Alexandra Calmy
Vice Dean of the Faculty of Medicine at UNIGE in charge of international and humanitarian medicine
Head of the HIV/AIDS Unit at HUG