Determinants of HIV-1 reservoir size and long-term dynamics during suppressive ART. Nature Communications.
Bachmann et al. aimed to examine how the size of the HIV-1 reservoirs changes in the long term and what factors affect the changes or size of the reservoir.
In this longitudinal observational study including patients from the Swiss HIV Cohort Study, the team of researchers carried out extensive test series on blood samples and the corresponding data from 1,057 people who have successfully been receiving ART for many years. The data collection provided at least three samples from each of the 1,057 people in order to measure the HIV reservoirs. On average, the samples were taken 1.5, 3.5, and 5.4 years after starting ART. For 412 individuals, data was available that enabled the status of the HIV reservoirs to be monitored over a period of ten years.
On average, the size of the HIV-1 reservoir during the first 5.4 years after starting ART decreased, with an estimated half-life of 5.6 years. During the observation period, the shrinking of the reservoirs leveled off considerably and appeared to reach a plateau. Contrary to expectations, however, 281 people (26.6%) in the analysis exhibited no decline but rather an increase in the size of the reservoirs despite successful antiretroviral therapy. Viral blips between 50 and 199 HIV-1 RNA copies/ml plasma occurred in 126 individuals within 0.5–1.5 years after initiation of ART and were significantly associated with a larger HIV-1 reservoir size. In addition to viral blips, high viral load pre-ART and slower time to viral suppression were found to be independently associated with a larger HIV-1 reservoir size. Nonwhite ethnicity was significantly associated with a smaller HIV-1 reservoir size, while HIV-1 non-B subtype only showed a significant association with a small HIV-1 reservoir in the univariable model.
In conclusion, this study found a small but continuous decay of the HIV-1 reservoir after initiation of suppressive ART. The decay slowed down over time and approached a plateau. Strikingly, viral blips were related to larger reservoirs and a less pronounced reduction of them over time. These blips were previously considered clinically irrelevant or negligible, but the study shows that these are biologically significant.