Postpartum viral load rebound in HIV-1-infected women treated with highly active antiretroviral therapy: AIDS Clinical Trials Group Protocol A5150.

BACKGROUND: Pregnancy may lead to increases in HIV-1 RNA levels postpartum. The AIDS Clinical Trials Group (ACTG) A5150 study was designed to characterize the incidence of viral load rebound during the immediate 24 weeks postpartum and explore factors associated with viral load rebound. METHODS: We enrolled pregnant women in the United States who were ≥13 years of age, between 22 to 30 weeks gestation, and who planned to be on stable highly active antiretroviral therapy (HAART) for ≥8 weeks predelivery and to continue this therapy after delivery for the duration of the study. Choice of antiretrovirals (ARVs) was determined by the primary HIV provider. Viral load rebound was defined as an increase of ≥0.7 log10 (5-fold) from the average of the weeks 34 and 36 gestation viral loads to week 24 postpartum or an absolute increase to ≯500 copies/mL for those with viral load <50 copies/mL. RESULTS: Eighty-four women enrolled for postpartum follow-up. Sixty-three had follow-up and viral load obtained through week 24 postpartum. Overall, 18/63 (28.6%; 95% confidence interval [CI], 17.9-41.4) met criteria for viral load rebound. Nineteen of the 63 women made changes or discontinued their ARV regimen prior to week 24 postpartum. For those who remained on stable ARVs, rebound occurred in 8/44 (18.2%; 95% CI, 8.2-32.7) compared with 10/19 (52.6%; 95% CI, 28.9-75.5) who did not remain on a stable ARV regimen. CONCLUSIONS: In the early postpartum period, HIV-1-infected women commonly have increases in viral load. Unplanned changes in ARV regimens and discontinuations of treatment are frequent.

Comparison of once-daily versus twice-daily combination antiretroviral therapy in treatment-naive patients: results of AIDS clinical trials group (ACTG) A5073, a 48-week randomized controlled trial.

BACKGROUND: Dosing frequency is an important determinant of regimen effectiveness. Methods. To compare efficacy of once-daily (QD) versus twice-daily (BID) antiretroviral therapy, we randomized human immunodeficiency virus (HIV)-positive, treatment-naive patients to lopinavir-ritonavir (LPV/r) administered at a dosage of 400 mg of lopinavir and 100 mg of ritonavir BID (n = 160) or 800 mg of lopinavir and 200 mg of ritonavir QD (n = 161), plus either emtricitabine 200 mg QD and extended-release stavudine at a dosage of 100 mg QD or tenofovir at a dosage of 300 mg QD. Randomization was stratified by screening HIV RNA level <100,000 copies/mL versus > or = 100,000 copies/mL. The primary efficacy end point was sustained virologic response (SVR; defined as reaching and maintaining an HIV RNA level <200 copies/mL) through week 48. RESULTS: Subjects were 78% male, 33% Hispanic, and 34% black. A total of 82% of subjects completed the study, and 71% continued to receive the initially assigned dosage schedule. The probability of SVR did not differ significantly for the BID versus QD comparison, with an absolute proportional difference of 0.03 (95% confidence interval [CI], -0.07 to 0.12). The comparison depended on the screening RNA stratum (P=.038); in the higher RNA stratum, the probability of SVR was significantly better in the BID arm than in the QD arm: 0.89 (95% CI, 0.79-0.94) versus 0.76 (95% CI, 0.64-0.84), a difference of 0.13 (95% CI, 0.01-0.25). Lopinavir trough plasma concentrations were higher with BID dosing. Adherence to prescribed doses of LPV/r was 90.6% in the QD arm versus 79.9% in the BID arm (P<.001). Conclusions. Although subjects assigned to QD regimens had better adherence, overall treatment outcomes were similar in the QD and BID arms. Subjects with HIV RNA levels > or =100,000 copies/mL had better SVR with BID regimens at 48 weeks, which suggests a possible advantage in this setting for more frequent dosing. Clinical trial registration. ClinicalTrials.gov registration number: NCT00036452.

Substitution of nevirapine because of efavirenz toxicity in AIDS clinical trials group A5095.

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. Clinical trials registration. NCT00013520 .