Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy.

OBJECTIVES: Long-acting formulations of cabotegravir (CAB) and rilpivirine (RPV) have demonstrated efficacy in Phase 3 studies. POLAR (NCT03639311) assessed antiviral activity and safety of CAB+RPV long-acting administered every 2 months (Q2M) in adults living with HIV-1 who previously received daily oral CAB+RPV in LATTE (NCT01641809). DESIGN: A Phase 2b, multicenter, open-label, rollover study. METHODS: LATTE participants with plasma HIV-1 RNA less than 50 copies/ml who completed at least 300 weeks on study were eligible. Participants elected to switch to either CAB+RPV long-acting Q2M or daily oral dolutegravir/RPV for maintenance of virologic suppression. The primary endpoint was the proportion of participants with HIV-1 RNA greater than or equal to 50 copies/ml at Month 12 (M12) per the Food and Drug Administration Snapshot algorithm. The incidence of confirmed virologic failure (CVF, two consecutive HIV-1 RNA measurements greater than or equal to 200 copies/ml), as well as safety, laboratory, and patient-reported outcomes (HIV Treatment Satisfaction and preference questionnaires) were also assessed. RESULTS: Of 97 participants enrolled, 90 chose to receive CAB+RPV long-acting and seven chose dolutegravir/RPV. At M12, no participant had HIV-1 RNA greater than or equal to 50 copies/ml or met the CVF criterion in either treatment group. No new safety signals were identified. Total treatment satisfaction was high at Baseline and remained stable through M12 across both treatment groups. Overall, 88% (n = 77/88) of long-acting arm participants preferred CAB+RPV long-acting to oral CAB+RPV. CONCLUSION: CAB+RPV long-acting maintained virologic suppression in participants who had previously received daily oral CAB+RPV for at least 5 years in LATTE, with a favorable safety profile. Most participants preferred CAB+RPV long-acting to their prior oral CAB+RPV regimen at M12.

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.

Predictors of death and survival duration among a sample of persons living With HIV/AIDS.

A follow-up study was conducted on a sample of 120 ethnically diverse HIV-positive men and women first interviewed in 2000. Participant survival and death rates were ascertained from death records and analyses were performed to identify demographic and psychosocial predictors of survival from the original data. Consistent with past studies, factors associated with survival were age, CD4 count, years HIV positive, and lower alcohol use. Two analyses identified use of professional counseling as a unique factor associated with reduced risk of death. Contrary to our hypotheses, the results from these analyses did not suggest that social groups with fewer economic and institutional resources or those with limited access to highly active retroviral therapy (HAART) therapies were at reduced risk of survival.

Unsafe sex among HIV positive individuals: cross-sectional and prospective predictors.

A follow-up study was conducted on a sample of 120 ethnically diverse HIV positive men and women first interviewed in 2000. Of the 86 survivors, 37 (43%) were able to be contacted 7-8 years later to conduct an exploratory examination of cross-sectional and prospective predictors of unsafe sexual behavior. Predictors that emerged as significant in the two cross-sectional analyses and the prospective analysis tended to be different variables, perhaps underscoring changing needs, perceptions, and behaviors among HIV positive persons over time. The cross-sectional analysis conducted at the baseline time frame showed a considerable number of significant correlates of unsafe sex, including several demographic/background variables. The cross-sectional analysis conducted on data collected 7 years later, on the other hand, showed far fewer significant correlates of unsafe sex, none of which were demographic/background variables, and which tended to be different correlates than those found in the baseline cross-sectional analysis. Significant predictors in the prospective analysis tended to be social support factors. This different pattern of prediction may be important to those designing interventions to influence risky sexual behavior.