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Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4+ T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4+ T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4+ cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly. [ABSTRACT FROM AUTHOR]

The Patient Medication Adherence Questionnaire Version 1.0 (PMAQ-V1.0) is a patient-reported adherence instrument to assess medication-taking behaviors and identify barriers to adherence with antiretroviral therapy. To assess the correlation between adherence and virologic outcome, the PMAQ-V1.0 was administered to 194 antiretroviral-experienced adults with HIV infection enrolled in a 16-week evaluation of protease inhibitor-containing regimens featuring a lamivudine/zidovudine combination tablet. At baseline, plasma HIV-1 RNA levels were less than 10,000 copies/mL and CD4(+)-cell counts were equal to or greater than 300 x 10(6)/L; patients had been receiving a conventional regimen of lamivudine + zidovudine (separately) plus a protease inhibitor for at least 10 weeks immediately prior to the study. Forty-eight percent of patients who reported missing at least one dose of a nucleoside reverse-transcriptase inhibitor (NRTI) during the study had detectable plasma HIV-1 RNA, compared with 26% of patients who reported no missed doses (P = .002). Patients who missed at least one dose of an NRTI or protease inhibitor were 2.5 times more likely to have quantifiable HIV-1 RNA than those who reported no missed doses. Patients who reported fewer barriers and more motivators to adherence had better virologic outcomes (P = .001). Several dimensions of the PMAQ-V1.0 did not function as well as hypothesized. In this study, self-reported adherence derived from the PMAQ-V1.0 predicted virologic outcomes, but further refinement of the dimensions appears warranted. [ABSTRACT FROM AUTHOR]

A correction to the article "Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy," by N. M. Archin and colleagues is presented.