Combination ART During Early Stage of HIV May Preserve CD4 Helper T Cells

Instituting combination antiretroviral treatment (ART) during early stages of HIV infection may generate functional CD8 “killer” T-cells and preserve CD4 helper T cells, which are the virus’s primary target, according to a new study from Massachusetts General Hospital.

The study, which was conducted among South African women at risk for contracting the virus, set out to examine whether the typical process of HIV infection suppression, in which the infection induces a massive CD8 T cell response that suppresses viral levels, could be subverted by early institution of ART.

"In a sense, this study shows that limiting the amount of virus the immune system encounters can stimulate much more potent CD8 T cell responses, leading to the development of long-term immune memory," says Bruce Walker, MD, senior author of the report. "The results have implications for HIV vaccine development, as this kind of functional immunity to HIV is what we would need from a vaccine."

Investigators enrolled a group of participants through the Females Rising Through Education, Support, and Health (FRESH) in KwaZulu-Natal, the South African province with one of the world’s highest HIV infection rates. The participants were women, ages 18 to 23, who were not in school or employed, were sexually active, and were HIV negative at the time of enrollment. Participants received HIV testing twice a week.

Hyperacute HIV infection was detected in 46 of the participants. Twenty-six of these participants began receiving ART within 24 to 48 hours of initial detection, 8 participants began receiving ART at later stages of infection, and 12 began treatment when CD4 T cells dropped below 350, the standard treatment guideline for South Africa at the time.

Results indicated that, while immediate HIV-specific CD8 T cell response of women receiving early ART was much less intense than those whose treatment began later, that response remained functional and persistent. This was indicated by continued expression of genes associated with key antiviral cytokines. Early ART also altered the maturation of HIV-specific CD8 T cells towards generation of effective antiviral T cell memory and promoted robust HIV-specific CD4 T cell responses.

According to Walker, understanding what constitutes a 'good' immune response to HIV gives us important information for vaccine design and could guide the development of interventions to achieve these kinds of responses in chronic infection.

Reference

Early antiretroviral treatment may preserve key immune responses to HIV [press release]. ScienceDaily website. Published May 22, 2019. https://www.sciencedaily.com/releases/2019/05/190522141810.htm. Accessed May 23, 2019.