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IDWeek 2014: Earlier Treatment, NNRTI Use Predict Slower HIV Rebound After Stopping ART

HIV viral load usually begins to rise again within 4 to 8 weeks after stopping antiretroviral therapy (ART), though starting treatment earlier in the course of infection and using a non-nucleoside reverse transcriptase inhibitor (NNRTI) may delay viral rebound, according to study findings presented at IDWeek 2014 last week in Philadelphia.

Researchers are studying various approaches to achieve a "functional cure" for HIV, which would allow people to remain off ART for a substantial period of time without disease progression. Such studies ultimately require participants to undergo treatment interruption to see if the virus returns, and it is useful to know the characteristics of typical viral rebound as a basis of comparison.

Jonathan Li from Brigham and Women's Hospital and colleagues performed a pooled analysis of AIDS Clinical Trials Group (ACTG) analytic treatment interruption studies to evaluate the timing of HIV rebound and CD4 T-cell loss.

They aimed to compare a "monitored antiretroviral pause" (MAP) strategy, in which ART is resumption once a specified viral load threshold is reached, versus an analytic treatment interruption (ATI) strategy that lasts a specified amount of time or allows the virus to return to its previous set-point before restarting treatment. The MAP strategy may be safer for study participants, they hypothesized.

This analysis included a total of 235 participants in 6 ACTG treatment interruption studies. Patients were included if they were on suppressive ART with HIV RNA <50 copies/mL and received no immunological or immune-based interventions such as vaccines. Two-thirds had started ART during chronic infection, 14% did so during acute infection, and 20% did so during recent or early infection.

Most participants were men, about 70% were white, and the median age was 41 years. At baseline, median CD4 counts ranged from approximately 800 cells/mm³ among those who started ART during chronic infection to more than 900 cells/mm³ among those who started during acute infection. A majority of people (60%) who started ART during chronic infection were on NNRTI-based regimens, compared with only 6% of those who started treatment sooner.

The researchers looked at 2 primary definitions of viral rebound: confirmed viral load >200 copies/mL, or a single viral load >1000 copies/mL.

Results

• While a majority of participants had detectable viral load by week 4 after stopping ART, a subset of people showed more durable viral suppression.
• Using a viral load threshold of either 200 or 1000 copies/mL, approximately 35% had undetectable HIV RNA at 4 weeks, about 10% did so at 8 weeks, and 6% were still undetectable at 12 weeks.
• Participants who started ART during acute or recent infection were significantly more likely to still have viral load <200 copies/mL at 12 weeks than those who started during chronic infection (about 13% vs 3%, respectively).
• People taking NNRTI-based regimens were significantly more likely to have viral load <200 copies/mL at 4 weeks than those using other types of antiretrovirals (44% vs 13%, respectively)
• Although CD4 counts declined slowly, they were higher when viral load became detectable than they were at the end of a timed treatment interruption -- indicating that losses were smaller using a MAP rather than an ATI strategy.
• People who had previously fallen to lower CD4 cell nadirs (lowest-ever levels) had larger CD4 declines during treatment interruption.

"Although most HIV+ patients have viral rebound within 4-8 weeks of stopping ART, a subset maintained drug-free remission for longer periods of time," the researchers concluded. "Participants treated during acute/recent HIV infection were more likely to maintain virologic suppression after treatment interruption."

"Compared with the traditional ATI approach, a MAP strategy is associated with smaller declines in CD4+ counts," they continued. "Future studies should assess virologic and immunologic determinants of delayed HIV rebound using a MAP strategy."

10/22/14

Reference

J Li, E Aga, R Bosch, et al. HIV Rebound Kinetics and CD4+ T-Cell Loss after Treatment Interruption: A Pooled Analysis of Six AIDS Clinical Trials Group (ACTG) Studies. IDWeek 2014. Philadelphia, October 8-12, 2014. Abstract 541.