The first results of the NAMSAL (New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-income countries) study, carried out by Swiss, French and Cameroonian teams, allowed the World Health Organization (WHO) to review its recommendations for the treatment of AIDS in order to better adapt them to the most diverse contexts.
Until recently, WHO recommended two drugs – Dolutegravir and Efavirenz – for the treatment of HIV infection. However, these two treatments have never been compared under conditions commonly found in countries with a high HIV prevalence. The NAMSAL study carried out jointly by the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG) in Switzerland, the Institut de recherche pour le développement (IRD) in France and the Central Hospital of Yaoundé in Cameroon with 613 patients from different Cameroon hospitals, now eliminates this ambiguity. If the two molecules reduce the viral load of the patients almost equally, the risk of developing resistance to treatment is lower with Dolutegravir. These results which can be read in the New England Journal of Medicine, provided the WHO with the first concrete data on the subject. They also underline the need to conduct high-quality studies among the populations involved, and not only with patients living in high-income countries, despite the operational complexity of such studies.
There are many antiretroviral drugs on the market used to reduce the viral load of HIV (the number of viruses per ml of blood) to an undetectable level; among the most used treatments, efavirenz, which exists since 1998, and the last Dolutegravir, introduced in 2013. “Although the two drugs are well known, they have never been compared to each other in low-income countries”, says Professor Alexandra Calmy, deputy director of the UNIGE School of Medicine, responsible for international and humanitarian medicine and head of the HIV/AIDS unit of HUG, who participated in this work. “We have therefore decided to do so with the support of ANRS and Unitaid to base international recommendations on concrete evidence.”
A double-blind study
The NAMSAL study was conducted in Cameroon between July 2016 and October 2018. 613 people with HIV who had never received treatment were randomized to one of two recommended therapies: a daily dose of Dolutegravir or a dose of 400 mg Efavirenz (a dose lighter than the usual dose of 600 mg to reduce adverse reactions), in combination with two other molecules (triple therapy). Although the results in terms of viral load after 48 months of treatment are similar between the two groups – about three-quarters of patients have seen their viral load fall to an undetectable level – the difference lies in the resistance to the virus in patients for whom the treatment did not work as desired. “Dolutegravir does not cause resistance mutations in the virus and therefore allows the option of other treatments,” says Eric Delaporte, a professor at Montpellier University Hospital and the IRD, who led this work. Efavirenz, on the other hand, has triggered important resistance mechanisms, which can be problematic: the people affected are therefore more difficult to treat and can also transmit to others a much stronger virus”.
Taking into account the specificities of populations
The results of the NAMSAL study show that the effect of both drugs on viral load is lower than expected. The clinical studies for approval are conducted on Western patients, the vast majority of whom are men, who also benefit from early diagnosis and good overall health,” explains Dr. Charles Kouanfack of Yaoundé Central Hospital and first author of the study. “Our patients are very different: two-thirds of them are women who are screened late and therefore have a very high initial viral load, which often receive few medical checks. Treatments take longer to function.
These findings illustrate the importance of these studies in the development of international recommendations. “We should have representative data of the populations receiving treatment in all their diversity and not select the people included in the studies according to very narrow criteria”, says Alexandra Calmy, who is also a WHO expert on HIV/AIDS, along with Professor Delaporte. “I would also like to stress the importance of not excluding women from clinical trials, especially when they make up the majority of patients involved.” Without these data, the WHO could not recommend one drug over another. Today, the United Nations agency clearly recommends Dolutegravir for the reasons specified in the study. The update of its recommendations, made in July 2019 after the publication of this work, will now allow countries and funding agencies to negotiate attractive prices with generic producers of Dolutegravir and combinations based on this molecule.