Earlier Antiretroviral Therapy Leads to Lower HIV Reservoirs

June 6, 2014

An open access paper published in the Journal of Infectious Diseases reports that earlier HIV suppression by ART is associated with significantly smaller HIV reservoirs in perinatally infected youths. The study, by Katherine Luzuriaga and colleagues, was initially presented at CROI last year and compared two groups of four individuals: one group started ART at 0.5–2.6 months of age and the other at 6-14.7 years of age. HIV DNA levels were significantly lower in the early-treated group, and replication-competent virus could only be detected in one out of the four, at a very low level, but was found in all of the late-treated study participants. Additionally, there was evidence of a decrease in HIV DNA levels over time in the early-treated group. At this year's CROI, Deborah Persaud described a similar but much larger analysis that echoed these findings, and also identified negative or indeterminate HIV antibody tests as a marker for smaller reservoirs (the presentation can be viewed via webcast).

Both the Journal of Infectious Diseases paper and an accompanying commentary by Jonathan Li and Rajesh Gandhi note that the results are consistent with prior studies in adults demonstrating that early initiation of ART is associated with a significantly lower HIV reservoir (for two examples, see the study abstract from  Vivek Jain et al, and the study abstract from Laurent Hocqueloux et al). One implication is that some early-treated individuals may ultimately be able to safely interrupt ART, but the authors emphasize that this needs to be tested in carefully conducted clinical trials. Several cautionary examples of HIV rebound despite undetectable or extremely low reservoirs prior to ART interruption are cited, including the Boston patients and a case report from the laboratory of Tae-Wook Chun.

An additional example involving a 3-year-old child started on ART within 72 hours after birth was reported recently at the Canadian Association for HIV Research conference. According to an article in the Globe & Mail, an ART interruption was prompted by adherence difficulties and viral load rebounded from undetectable levels to 7,797 copies in two weeks and 11,358 copies in four (although the article uses the word "skyrocketed," these viral load levels are actually low for untreated pediatric HIV infection and the apparent increase from the second to fourth week is small and within the variability of the assay). ART has since been restarted and viral load once again suppressed. The researchers presenting this case noted some differences with the Mississippi baby, including a longer time to viral load suppression (six months versus 19 days) and an instance of a borderline detectable viral load prior to the ART interruption.

A clinical trial investigating immediate ART in babies born to HIV-positive mothers who did not receive prevention of mother-to-child transmission (PMTCT) is about to be launched by the International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Network. An entry for the trial is now posted in the database and additional information, including the protocol, is available on the IMPAACT website. The primary aim is to assess whether the apparent remission of HIV infection that has been achieved in the Mississippi baby can be duplicated in other infants.

Update 6/9/14: The IMPAACT trial investigators have published a "personal view" article in Lancet Infectious Diseases that discusses some of the ethical issues raised by their research. The article is accessible free of charge but requires registration for the website.

Richard Jefferys is the coordinator of the Michael Palm HIV Basic Science, Vaccines & Prevention Project Weblog at the Treatment Action Group (TAG). The original blog post may be viewed here.

This article was provided by Treatment Action Group. It is a part of the publication Michael Palm HIV Basic Science, Vaccines & Cure Project.

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