A 48-week randomized phase 2b study evaluating cenicriviroc versus efavirenz in treatment-naive HIV-infected adults with C-C chemokine receptor type 5-tropic virus.

OBJECTIVE: To compare the efficacy, safety, and anti-inflammatory effects of cenicriviroc (CVC), an oral, once-daily C-C chemokine receptor types 5 and 2 antagonist, with those of efavirenz (EFV) in treatment-naive, HIV-1-infected adults. DESIGN: A 48-week, randomized, double-blind, double-dummy phase 2b trial at 43 institutions (USA and Puerto Rico). METHODS: Study participants (HIV-1 RNA ≥1000 copies/ml, CD4 cell count ≥200 cells/µl, C-C chemokine receptor type 5-tropic virus) were randomized 2 : 2 : 1 to CVC 100 mg (CVC100), CVC 200 mg (CVC200), or EFV 600 mg, each administered with emtricitabine/tenofovir disoproxil fumarate. Key end points were virologic success (HIV-1 RNA <50 copies/ml) at week 24 (primary) and week 48 (secondary), safety/tolerability at weeks 24 and 48. Study sites and patients remained blinded until week 48. RESULTS: A total of 143 patients were randomized (CVC100, n = 59; CVC200, n = 56; EFV, n = 28). Virologic success was obtained at week 24 in 76, 73, and 71% of study participants for CVC100, CVC200, and EFV, respectively (all P > 0.05 versus EFV), and at week 48 in 68, 64, and 50%, respectively (all P > 0.05 versus EFV). Resistance mutations emerged in five and zero CVC and EFV-treated study participants, respectively. Virologic nonresponse and nucleoside reverse transcriptase inhibitor resistance decreased when CVC minimum plasma concentration was at least 47.8 ng/ml. Treatment-related adverse events of at least grade 2 and discontinuations because of adverse events were less frequent in CVC-treated study participants. Total and low-density lipoprotein cholesterol decreased with CVC, but increased with EFV. C-C chemokine ligand type 2 (CCL2) (aka monocyte chemotactic protein-1) increased in a dose-dependent manner, whereas soluble CD14 levels decreased with CVC. CONCLUSION: CVC showed efficacy and favorable safety in treatment-naive HIV-1-infected study participants, supporting selection of CVC200 for phase 3 studies. TRIAL REGISTRATION: NCT01338883.

Insights on GRACE (Gender, Race, And Clinical Experience) from the patient's perspective: GRACE participant survey.

The Gender, Race And Clinical Experience (GRACE) study was conducted between October 2006 and December 2008 to evaluate sex- and race-based differences in outcomes after treatment with a darunavir/ritonavir-based antiretroviral regimen. Between June 2010 and June 2011, former participants of the GRACE trial at participating sites were asked to complete a 40-item questionnaire as part of the GRACE Participant Survey study, with a primary objective of assessing patients' characteristics, experiences, and opinions about participation in GRACE. Of 243 potential survey respondents, 151 (62%) completed the survey. Respondents were representative of the overall GRACE population and were predominantly female (64%); fewer were black, and more reported recreational drug use compared with nonrespondents (55% vs. 62% and 17% vs. 10%, respectively). Access to treatment (41%) and too many blood draws (26%) were reported as the best and worst part of GRACE, respectively. Support from study site staff was reported as the most important factor in completing the study (47%). Factors associated with nonadherence, study discontinuation, and poor virologic response in univariate analyses were being the primary caregiver for children, unemployment, and transportation difficulties, respectively. Patients with these characteristics may be at risk of poor study outcomes and may benefit from additional adherence and retention strategies in future studies and routine clinical care.

Meeting notes from the 3rd IAS Conference. New drugs.

CCR5 antagonists created quite a buzz at IAS: several are entering phase III trials and could be available in the next 2 to 3 years.