Virus World

There is a “window of opportunity” in the weeks after someone is infected with HIV where treatment may lead to better control later on, researchers say. Treatment for human immunodeficiency virus (HIV) four weeks after infection may make it possible to control the virus without medication in the long term, a new study has shown. The finding reinforces the importance of detecting HIV early, according to researchers from the French Institut Pasteur, CEA, Inserm, University of Paris Cité, and the University of Paris-Saclay. Treatment for HIV is called antiretroviral therapy (ART) and can be taken as a pill or an injection. The goal is to reduce a person’s viral load to an undetectable level so the person has no risk of transmitting HIV.

This therapy is now so effective that it can fully control the virus, with researchers even exploring ways to cure it. This latest study looked at the impact of early treatment on primates with simian immunodeficiency virus (SIV), which is closely related to HIV. The researchers found that very early treatment for two years led to controlling the virus even after treatment was interrupted. “We show an association between early treatment and control of the infection after treatment is stopped, and our study indicates the existence of a window of opportunity to promote remission of HIV infection,” Asier Sáez-Cirión, head of the Institut Pasteur’s viral reservoirs and immune control unit and co-senior author of the study, said in a statement. A previous 2013 study in humans had shown a similar possibility, suggesting that early treatment could allow people to stop treatment, with the virus in a “state of remission”. The latest study also showed that the benefits of early treatment were lost if therapy was started just five months later. The findings were published in the scientific journal Nature Communications.

The AIDS epidemic has been a global public health issue for more than 40 years and has resulted in ~40 million deaths. AIDS is caused by the retrovirus, HIV-1, which is transmitted via body fluids and secretions. After infection, the virus invades host cells by attaching to CD4 receptors and thereafter one of two major chemokine coreceptors, CCR5 or CXCR4, destroying the host cell, most often a T lymphocyte, as it replicates. If unchecked this can lead to an immune-deficient state and demise over a period of ~2–10 years. The discovery and global roll-out of rapid diagnostics and effective antiretroviral therapy led to a large reduction in mortality and morbidity and to an expanding group of individuals requiring lifelong viral suppressive therapy. Viral suppression eliminates sexual transmission of the virus and greatly improves health outcomes.

HIV infection, although still stigmatized, is now a chronic and manageable condition. Ultimate epidemic control will require prevention and treatment to be made available, affordable and accessible for all. Furthermore, the focus should be heavily oriented towards long-term well-being, care for multimorbidity and good quality of life. Intense research efforts continue for therapeutic and/or preventive vaccines, novel immunotherapies and a cure. In HIV infection, the virus invades and destroys the immune system of the host. This Primer by Bekker and colleagues summarizes the epidemiology, mechanisms, diagnosis and treatment of HIV infection, and discusses patient quality of life and open research questions for this condition.

Published August 17, 2023:

https://www.nature.com/articles/s41572-023-00452-3 

Michelle Moorhouse, MB BCh, from Wits Reproductive Health and HIVInstitute, like many other physicians, started to notice that the numbers on the scale kept going up for her patients who were taking integrase inhibitors. Speaking from the podium here at the International AIDS Society (IAS) 2019 Conference on HIV Science, Moorhouse explained that "a real flurry" of reports started coming in about tenofovir alafenamide and dolutegravir being associated with weight gain.

Dolutegravir and tenofovir alafenamide can lead to weight gain, especially in women, according to new data that are changing the way researchers look at their study populations.  So the ADVANCE team worked with researchers from the New Antiretroviral and Monitoring Strategies in HIV Infected Adults in Low-income countries (NAMSAL) trial NCT02777229) to pull together all the weight-gain data accrued from their combined cohort of 1666 participants.  And they found a consistent story.

In the NAMSAL trial, weight gain was higher in the dolutegravir group than in the efavirenz group (5 kg vs 3 kg; P ≤ .001), and the mean increase in body mass index was greater in the dolutegravir group (1.7 vs 1.2 kg/m2; P ≤ .001). In the ADVANCE trial, weight gain was even more pronounced, but the pattern was the same: participants in the dolutegravir plus Descovy group gained more weight over 96 weeks than those in the dolutegravir plus Truvada group (8 kg vs 5 kg).