Evidence of Smaller HIV Reservoirs in a Ugandan Cohort
The size of the reservoir of replication-competent HIV that persists in individuals on ART has been described in several studies from North America, but no information has previously been presented from the African continent, where the burden of HIV infection is greatest. A study just published in Clinical Infectious Diseases by Jessica Prodger and colleagues takes a first step toward filling this gap, and the results may be surprising.
The researchers measured the size of the replication-competent HIV reservoir in a cohort of 70 individuals on suppressive ART in Rakai, Uganda, and compared the results to those obtained previously in a study involving 51 participants from Baltimore. On average, the reservoir was three-fold smaller: 0.36 infectious units per million cells (IUPM), compared to 1.08 IUPM. This translates into approximately one out of every 2.7 million CD4 T cells containing replication-competent HIV in the individuals in Rakai versus one out of every million cells among those in Baltimore.
In both cohorts, a higher set point viral load prior to treatment was associated with a larger HIV reservoir, while a longer duration of viral suppression due to ART was associated with a smaller reservoir. These findings indicate that key factors that influence the size of the reservoir are shared across the two settings.
The reasons for the difference in the average amount of replication-competent HIV detected remain to be elucidated, but the researchers note that there are differences between the populations in terms of "lifetime immunologic challenges, HIV-1 subtypes, and genetic background." Previous studies have documented environmentally driven differences in levels of immune activation when comparing Ugandan and Italian individuals living in Italy to those living in Uganda, raising the speculative possibility that elevated CD4 T cell activation and turnover might lessen opportunities for HIV to establish latency in long-lived, resting memory CD4 T cells (the cell type that generally harbors the bulk of the replication-competent HIV reservoir). Further research is urgently needed to better understand the results, since they may have significant implications for the prospects of curing HIV infection in the African setting.
A recent open access review article published in the Journal of the International AIDS Society by Theresa Rossouw and colleagues touches on similar themes, discussing considerations that are likely to be important for remission and cure research in low- and middle-income countries (LMIC). These include immune activation, uncontrolled HIV replication, viral subtype, co-infections, microbial translocation and nutrition. The authors argue strongly for the importance of expanding the global reach of current efforts, stating: "the inclusion of patients from high burden LMIC is essential for cure research." The fact that these two papers appeared within weeks of each other (they were published online May 23 and June 5, respectively) is a welcome slice of kismet, as they shed timely light on an important topic.
Richard Jefferys is project director at Treatment Action Group (TAG).