HIV infection continues to spread despite antiretroviral therapy

Fletcher CV. Proc Natl Acad Sci USA. 2014;doi:10.1073/pnas.1318249111.

  • February 11, 2014

Recent data suggest that HIV continues to replicate in lymphatic tissues of some individuals taking antiretroviral drugs considered fully suppressive, drawing on the idea that constant replication is caused by lower concentrations of antiretrovirals in lymphatic tissues compared with peripheral blood.

“We know the drugs we use today are effective because our patients are doing better and living longer, but these drugs cannot cure the infection. We wanted to know why and thought that maybe the drugs were not getting into the tissues where most virus replication is happening,” study researcher Timothy Schacker, MD, director of the program in HIV medicine at the University of Minnesota, said in a press release.

The study included 12 patients who were treated with antiretrovirals. Two patients had been previously treated but had been off ART for more than a year, and 10 patients had never received antiretrovirals before the study.

Six patients in the study received tenofovir-emtricitabine-efavirenz (Atripla; Bristol-Myers Squibb and Gilead Sciences); four received atazanavir (Reyataz, Bristol-Myers Squibb) and ritonavir (Norvir, AbbVie); and two received darunavir (Prezista, Janssen) and ritonavir.

Researchers took samples from lymph nodes, ileum and rectum, and peripheral blood to determine intracellular concentration after initiating therapy.

The study findings indicate commonly used antiretroviral drugs were less likely to penetrate lymphoid tissue cells than blood cells. Four patients exhibited a slower rate of decay of HIV from the follicular dendritic cell network, which signifies continued virus production during ART, and correlated to lower antiretroviral drug levels in lymphatic tissue cells during 6 months of therapy.

“Most HIV replicates in the lymph and gut tissues and that’s where we need to look to understand the efficacy of these drugs. The ongoing replication we found in the lymph and gut tissues we tested were directly correlated with the drug levels found there. This persistent low-level replication may be one case of the chronic immune activation we find in these patients, and is likely an important factor in accelerated aging, increased cardiovascular events and early mortality common in these patients,” study researcher Ashley Haase, MD, of the University of Minnesota, said in the release.

Disclosure: The researchers report no relevant financial disclosures.