Understanding the latent HIV-1 reservoir is critical for developing strategies for cure

1 October 2021

Immune activation, measured on CD8+ T cells, just prior to antiretroviral therapy (ART) initiation, was an independent predictor of the size of the replication-competent HIV-1 reservoir, according to a study by the collaborative team of researchers from CAPRISA and the Universities of Cape Town and North Carolina.  The study, Immunological correlates of the HIV-1 replication-competent reservoir size, was recently published in the journal Clinical Infectious Diseases.

Researchers carried out a longitudinal study of 20 women enrolled in the CAPRISA 002 acute infection cohort and quantified the frequency of resting CD4+ T-cells harbouring replication-competent HIV-1 after 5 years of suppressive ART that was initiated during chronic infection and investigated immune correlates of reservoir size.  Viral loads and CD4+ T-cell counts also predicted the size of the reservoir, but models that included immune activation improved their predictive value (Figure). 

This is important because the longer HIV infection proceeds, the more activation accumulates, and therefore early therapy in a less activated immune system may improve the chances of achieving an HIV cure. “The results are consistent with the hypothesis that the host immune milieu near the time of ART initiation plays an important role in shaping the durable reservoir of HIV infection that persists on ART,” says Dr Lyle McKinnon, Honorary Senior Scientist at CAPRISA. 

The latent HIV reservoir is a major barrier to curing HIV infection, and recent efforts have accelerated with respect to solving fundamental problems, such as where the reservoir is located, how best to measure it, when it is established, and ways that it can be targeted therapeutically. The new knowledge regarding the contribution of immune to activation to HIV reservoir formation may assist with the design of novel cure and/or therapeutic vaccine approaches.

For further reading see:
Ismail SD, et al. Immunological correlates of the HIV-1 replication-competent reservoir size. Clinical Infectious Diseases 2021. doi: 10.1093/cid/ciab587. https://pubmed.ncbi.nlm.nih.gov/34181706/


Figure: Correlations between model predictions and measured frequency of latently infected cells. Correlation between replication-competent HIV-1 in resting memory CD4+ T-cells [log10 (infectious units per million, IUPM)] and the predicted IUPM resting CD4+ T-cells over the time period from (A) acute infection to ART initiation (n=20), (B) over the final year prior to ART initiation (n=20), (C) acute infection to QVOA (n=20), and (D) from a year prior to ART initiation to QVOA (n=20). Non-parametric Spearman rank correlation coefficients and the P-value of the correlation are given at the bottom of each panel.