In HIV-1-infected, treatment-experienced patients, vicriviroc demonstrated potent virologic suppression through 24 weeks. The relationship of vicriviroc to malignancy is uncertain. Further development of vicriviroc in treatment-experienced patients is warranted.

Objective: Prior studies have shown improved neurocognition with initiation of antiretroviral treatment (ART) in HIV. We hypothesized that stopping ART would be associated with poorer neurocognitive function. Methods:Neurocognitive function was assessed as part of ACTG 5170, a multicenter, prospective observational study of HIV-infected subjects who elected to discontinue ART. Eligible subjects had CD4 count Ͼ350 cells/mm 3 , had HIV RNA viral load Ͻ55,000 cp/mL, and were on ART (Ն2 drugs) for Ն6 months. Subjects stopped ART at study entry and were followed for 96 weeks with a neurocognitive examination.Results: A total of 167 subjects enrolled with a median nadir CD4 of 436 cells/mm 3 and 4.5 median years on ART. Significant improvements in mean neuropsychological scores of 0.22, 0.39, 0.53, and 0.74 were found at weeks 24, 48, 72, and 96 (all p Ͻ 0.001). In the 46 subjects who restarted ART prior to week 96, no significant changes in neurocognitive function were observed. Conclusion: Subjects with preserved immune function found that neurocognition improved signif-icantly following antiretroviral treatment (ART) discontinuation. The balance between the neurocognitive cost of untreated HIV viremia and the possible toxicities of ART require consideration. Classification of evidence:This study provides Class III evidence that discontinuing ART is associ- -1266GLOSSARY ACTG ϭ AIDS Clinical Trials Group; ART ϭ antiretroviral treatment; EFV ϭ efavirenz; HAART ϭ highly active antiretroviral therapy; HAD ϭ HIV-associated dementia; NP ϭ neuropsychological summary score; TI ϭ treatment interruption; VL ϭ viral load.

Disease progression after TI was low in this cohort. A higher nadir in CD4(+) cell count, a lower HIV load before ART, and an HIV load < or =50 copies/mL at the time of TI predicted a longer time to the primary end point.

The contribution of host T-cell immunity and HLA class I alleles to the control of human immunodeficiency virus (HIV-1) replication in natural infection is widely recognized. We assessed whether vaccine-induced T-cell immunity, or expression of certain HLA alleles, impacted HIV-1 control after infection in the Step MRKAd5/HIV-1 gag/pol/nef study. Vaccine-induced T cells were associated with reduced plasma viremia, with subjects targeting ≥3 gag peptides presenting with half-log lower mean viral loads than subjects without Gag responses. This effect was stronger in participants infected proximal to vaccination and was independent of our observed association of HLA-B*27, -B*57 and -B*58:01 alleles with lower HIV-1 viremia. These findings support the ability of vaccine-induced T-cell responses to influence postinfection outcome and provide a rationale for the generation of T-cell responses by vaccination to reduce viremia if protection from acquisition is not achieved. Clinical trials identifier: NCT00095576.

The enhanced sensitivity Trofile assay was used to re-test co-receptor usage at study screening and entry for the 118 ACTG A5211 treatment-experienced subjects who had CCR5-tropic (R5) virus by the original Trofile assay at study screening. Among 90 vicriviroc recipients, a significantly (P<0.001) greater mean reduction in HIV-1 RNA was observed in 72 subjects with R5 virus versus 15 subjects reclassified with dual/mixed-tropic viruses at screening: −1.11 vs. −0.09 (day 14), −1.91 vs. −0.57 (week 24) log10 copies/mL, respectively. Results suggest that the enhanced sensitivity assay is a better screening tool for determining patient eligibility for CCR5 antagonist therapy.

There was a greater effect of nonadherence on virologic failure in blacks given efavirenz-containing regimens than in whites. Self-reported adherence and QOL are independent predictors of virologic failure.

In AIDS Clinical Trials Group A5095, 9% of participants who experienced an adverse event related to efavirenz substituted nevirapine. Most adverse events resolved; 15 participants ultimately discontinued nevirapine therapy. Grade 3/4 hepatotoxicity was observed in 14% of individuals who substituted nevirapine, compared with 6% who continued efavirenz therapy. Substitution of nevirapine because of efavirenz toxicity was generally safe and efficacious.

Using standard and ultrasensitive techniques, we detected nonnucleoside reverse-transcriptase inhibitor–associated resistance mutations in 11 (20%) of 54 subjects who discontinued virologically suppressive nonnucleoside reverse-transcriptase inhibitor–containing antiretroviral therapy. Resistance was detected in 45% and 14% of subjects with a baseline human immunodeficiency virus type 1 RNA level of 51–400 copies/mL and ≤50 copies/mL, respectively. Mutations remained detectable for at least 48 weeks in some subjects.