Dolutegravir + Lamivudine vs. Dolutegravir + Tenofovir Disoproxil Fumarate/Emtricitabine: Very-Low-Level HIV-1 Replication through 144 Weeks in the GEMINI-1 and GEMINI-2 Studies.

In GEMINI-1/-2, dolutegravir + lamivudine was non-inferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in achieving viral suppression (viral load [VL] < 50 copies/mL) in treatment-naive adults. Abbott's RealTime HIV-1 assay provides quantitative VL (40-10,000,000 copies/mL) and qualitative target detected or target not detected (TND) for VL < 40 copies/mL. This post hoc analysis assessed very-low-level viremia and "blips" through Week 144. Proportions with VL < 40 copies/mL and TND are presented overall and by baseline VL and CD4+ cell count. "Blips" (single VL ≥ 50 to <200 copies/mL with adjacent values < 50 copies/mL) were assessed from Day 1 after VL suppression and from Weeks 48 through to 144. Proportions with TND increased through Week 48 and were similar between groups at all visits (Week 144: dolutegravir + lamivudine, 451/716 [63%]; dolutegravir + TDF/FTC, 465/717 [65%]). By observed analysis, TND rates were similar between groups across baseline subgroups. Through Week 144, proportions with ≥1 "blip" were generally comparable for dolutegravir + lamivudine vs. dolutegravir + TDF/FTC from Day 1 (15% vs. 20%) and from Week 48 (7% vs. 11%). Through 144 weeks, the proportions with TND or "blips" were similar between dolutegravir + lamivudine and the three-drug comparator, reinforcing the efficacy and durability of dolutegravir + lamivudine.

Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study.

At week 48 in the phase IIIb DAWNING study, the integrase strand transfer inhibitor (INSTI) dolutegravir plus 2 nucleoside reverse transcriptase inhibitors demonstrated superiority to ritonavir-boosted lopinavir in achieving virologic suppression in adults with HIV-1 who failed first-line therapy. Here, we report emergent HIV-1 drug resistance and mechanistic underpinnings among dolutegravir-treated adults in DAWNING. Population viral genotyping, phenotyping, and clonal analyses were performed on participants meeting confirmed virologic withdrawal (CVW) criteria on dolutegravir-containing regimens. Dolutegravir binding to and structural changes in HIV-1 integrase-DNA complexes with INSTI resistance-associated substitutions were evaluated. Of participants who received dolutegravir through week 48 plus an additional 110 weeks for this assessment, 6 met CVW criteria with treatment-emergent INSTI resistance-associated substitutions and 1 had R263R/K at baseline but not at CVW. All 7 achieved HIV-1 RNA levels of <400 copies/mL (5 achieved <50 copies/mL) before CVW. Treatment-emergent G118R was detected in 5 participants, occurring with ≥2 other integrase substitutions, including R263R/K, in 3 participants and without other integrase substitutions in 2 participants. G118R or R263K increased the rate of dolutegravir dissociation from integrase-DNA complexes versus wild-type but retained prolonged binding. Overall, among treatment-experienced adults who received dolutegravir in DAWNING, 6 of 314 participants developed treatment-emergent INSTI resistance-associated substitutions, with a change in in vitro dolutegravir resistance of >10-fold and reduced viral replication capacity versus baseline levels. This study demonstrates that the pathway to dolutegravir resistance is a challenging balance between HIV-1 phenotypic change and associated loss of viral fitness. (This study has been registered at ClinicalTrials.gov under identifier NCT02227238.).

A multistate trial of pharmacy syringe purchase.

Pharmacies are a potential site for access to sterile syringes as a means for preventing human immunodeficiency virus (HIV), but the type and extent of their utility is uncertain. To examine pharmacy syringe purchase, we conducted a standardized, multistate study in urban and rural areas of four states in which attempts to purchase syringes were documented. Of 1,600 overall purchase attempts, 35% were refused. Colorado (25%) and Connecticut (28%) had significantly lower rates of refusal than Kentucky (41%) and Missouri (47%). Furthermore, urban settings had higher rates of refusal (40%) than rural settings (31%, P < .01). Race and gender did not have a consistent impact on rates of refusal. Despite potential advantages of pharmacies as sites for access to sterile syringes, pharmacy purchase of syringes faces significant obstacles in terms of the practices in different jurisdictions.

Pharmacist ambivalence about sale of syringes to injection drug users.

OBJECTIVE: To examine pharmacists' attitudes and practices surrounding human immunodeficiency virus (HIV) prevention among injection drug users. DESIGN: Focus groups. SETTING: Urban and rural sites in Colorado, Connecticut, Kentucky, and Missouri. PATIENTS OR OTHER PARTICIPANTS: Eight focus groups, with 4 to 11 pharmacists participating in each group. INTERVENTIONS: Transcripts of focus group discussions were evaluated for common themes by the authors and through the use of NUD*IST. MAIN OUTCOME MEASURES: Willingness to sell syringes to all customers, views on syringe exchange programs (SEPs), knowledge of laws governing syringe sales and racial, ethnic, or gender biases in syringe selling practices. RESULTS: Two pharmacists established their own policies of selling syringes to everyone, and three expressed a willingness to have their pharmacies serve as SEPs. A total of 20% of the pharmacists expressed an interest in learning more about the efficacy of SEPs and distribution of syringes by pharmacists, and were willing to change their views based on this information. Many also indicated a general willingness to work with SEPs or to participate in the effort to curb the spread of HIV. However, a majority of pharmacists opposed having SEPs in their pharmacies and reported selling syringes only within specific limits: to known diabetics, to individuals who looked reasonable, or to individuals who presented a logical explanation. No racial, ethnic, or gender bias was observed. CONCLUSION: Opinions among pharmacists varied across and within sites. While a majority of pharmacists would not establish SEPs in their own pharmacies, nearly all would participate in other HIV-prevention programs. Educational programs for pharmacists may be valuable in HIV-prevention efforts.