Non-adherence to Antiretroviral Therapy Results in Persistent Viremia

HIV persists in a reservoir as reflected in the detection of residual HIV-1 viremia despite long-term antiretroviral therapy (ART).^1-3 However, it is not known whether noncompliance with ART plays a role in this residual viremia.

A new study recently published in the journal AIDS attempts to answer this question._⁴ The study evaluated the role of ART adherence on levels of residual HIV-1 viremia using the Research on Access to Care in the Homeless (REACH) cohort. This cohort prospectively enrolled patients infected with HIV from San Francisco.

The investigators assessed adherence to therapy by patients for whom a 3-drug combination had been prescribed. They did so by conducting unannounced visits to the participants in the community every 3 to 6 weeks to count the number of antiretroviral pills in their possession. The study included individuals who had at least 6 months of virologic suppression (less than 50 HIV-1 RNA copies/mL), were enrolled in the REACH Adherence Monitoring Cohort for at least 3 months, and had available plasma for the single-copy assay (SCA). This assay is a real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for HIV-1 RNA in plasma.

The SCA was performed on plasma samples that were previously found to have less than 50 HIV-1 RNA copies/mL from a time point that matched the inclusion criteria. The assay was also performed on an available plasma sample collected 1 to 3 months before the primary time point (median, 28 days; interquartile range, 28 to 31 days). The investigators examined the correlation between the change in viral loads and the average ART adherence in the interval between the two time points.

At the primary time point, 47% of participants had detectable residual HIV-1 virus in plasma. Average ART adherence over the past 2 months was significantly associated with levels of residual HIV viremia (Spearman r = –0.25; P = .04). On multivariate analysis, ART adherence over the past 2 months was significantly associated with residual viremia (P = .004), even after adjusting for duration of virologic suppression, CD4⁺ cell count, and the particular ART regimen.

Take-home message

The authors conclude that incomplete adherence with ART can be associated with higher levels of residual HIV-1 viremia. Primary care physicians should be cognizant of the consequences of incomplete adherence, including persistent viremia.

References
1. Palmisano L, Giuliano M, Nicastri E, etl al. Residual viraemia in subjects with chronic HIV infection and viral load <50copies/ml: the impact of highly active antiretroviral therapy. AIDS. 2005;19:1843–1847.
2. Palmer S, Maldarelli F, Wiegand A, et al. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci U S A. 2008;105:3879–3884.
3. Hatano H, Delwart EL, Norris PJ, et al. Evidence of persistent low-level viremia in long-term HAART-suppressed, HIV-infected individuals. AIDS. 2010;24:2535–2539.
4. Li JZ, Gallien S, Ribaudo H, et al. Incomplete adherence to antiretroviral therapy is associated with higher levels of residual HIV-1 viremia. AIDS. 2014;28:181-186.