Andrew R. Zolopa

We report week 96 results from a phase 3 trial of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF, n = 348) vs efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF, n = 352). At week 48, EVG/COBI/FTC/TDF was noninferior to EFV/FTC/TDF (88% vs 84%, difference +3.6%, 95% confidence interval: -1.6% to 8.8%). Virologic success (HIV-1 RNA <50 copies/mL) was maintained at week 96 (84% vs 82%, difference +2.7%, 95% CI: -2.9% to 8.3%). Discontinuation due to adverse events was low (5% vs 7%). Median changes in serum creatinine (mg/dL) at week 96 were similar to week 48. These results support the durable efficacy and long-term safety of EVG/COBI/FTC/TDF.

Potent antiretroviral therapy (ART) has transformed HIV infection into a chronic manageable disease, but drug resistance remains a common problem that limits the effectiveness and clinical benefits of treatment. With increasing experience with ART, the understanding of viral dynamics of HIV improved, and researchers learned how challenging HIV can be to control. With new-class and new-generation drugs, it is hoped that the lessons learned will be useful for limiting drug resistance and optimizing the use of ART for long-term management of HIV infection.

Background. This phase 2, randomized, active-controlled, 48-week study assessed the noninferiority of the human immunodeficiency virus (HIV) integras

Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined. A5164 was a randomized strategy trial of “early ART” - given within 14 days of starting acute OI treatment versus “deferred ART” - given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) ≥50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively. The difference in the primary endpoint did not reach statistical significance: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27–0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30–0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events. Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications. ClinicalTrials.gov NCT00055120

Testing for resistance to antiretrovirals is considered to be standard of care and is widely used in the management of human immunodeficiency virus (HIV)–infected persons. Despite the widespread use of resistance testing, the clinician still faces a number of challenges when applying these technologies in the optimal management of antiretroviral therapy. Both genotype and phenotype tests require interpretation, and available interpretative algorithms for genotypes and resistance cutoffs for phenotypes are incomplete and evolving. Even experts in HIV resistance do not completely agree in their interpretation of genotypes. Moreover, discordant results between genotypes and phenotypes are a common source of confusion when both tests are used to evaluate resistance in a patient. Finally, newer indicators, such as replication capacity, are clinically available and appear to have prognostic value, but how this in vitro measure should be used in the management of antiretroviral therapy remains to be fully defined.

Background. Resistance testing is considered standard of care in HIV medicine, but there is no standard interpretation system for genotype tests. We

In patients with failure of antiretroviral therapy that contains protease inhibitors, HIV-1 genotype is predictive of virologic response to subsequent therapy. This predictive capacity adds to that... Background: Tests for resistance to HIV drugs are available for clinical use; however, their predictive value has not been fully assessed. Objectives: To determine HIV-1 genotypic predictors of a v...