Tolerability is more important than simplicity for treatment durability.

INTRODUCTION: Many studies have shown the superiority of single tablet regimens (STRs) of antiretrovirals for the treatment of HIV in terms of efficacy, adherence and rate of hospitalisation as they offer a low pill burden and once daily dosing. Our objective was to compare the duration of first-line STRs to multi-tablet regimens. METHODS: From our clinical database, we selected patients initiating any of the major first-line regimens between 2007 and 2013. Two STRs, Atripla (ATP) and Complera (CPLR), were compared to three non-STRs: two NRTIs and raltegravir (RAL), atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r). The primary outcome was time to discontinuation of the first-line regimen. The association between regimen type and duration was estimated using Cox proportional hazards models adjusted for age, gender, baseline CD4, baseline viral load, risk factor, site and year of treatment initiation. RESULTS: A total of 743 patients (281 on STRs and 462 on non-STRs) were included. 693 (93%) were male and median age was 43 years. Median length of follow-up was 3.2 years. 56% of patients were MSM, 6% IDU and 6% from endemic countries. Patients on an STR were less likely to be IDU (p<0.024) and have a baseline HIV-RNA ≥100,000 copies/mL (p<0.011). Overall, 321 (43%) patients discontinued their regimen during the study period. The rate of discontinuation one year after starting ARV depends on the regimen: 29% for patients on 2NRTIs+DRV/r, 26% on ATP, 25% on 2NRTIs+ATV/r, 17% on 2NRTIs+RAL and 10% on CPLR (p<0.001). In the adjusted model, durability for STR and non-STR was equivalent (aHR=0.83, p=0.108). Compared to patients on ATP, patients on CPLR were less likely to discontinue (HR=0.58, p=0.070). No difference between ATP and the other regimens was observed: HR for 2NRTIs+RAL=0.92 (p=0.66), 2NRTIs+ DRV/r=1.16 (p=0.36), 2NRTIs+ATV/r=1.11 (p=0.46). CONCLUSIONS: Our findings suggest that STRs do not necessarily result in a more durable treatment. Even with a higher pill burden and/or twice daily dosing, patients initiating therapy with RAL or boosted-PI based regimens were not more likely to discontinue the first-line regimen compared to patients on an STR. Among the STR subgroups, the regimen with better known tolerability conferred more durable treatment. Limitations included our inability to adjust for the patient's adherence to a given regimen.

Abacavir/lamivudine fixed-dose combination with ritonavir-boosted darunavir: a safe and efficacious regimen for HIV therapy.

BACKGROUND: Current treatment guidelines recommend the use of tenofovir (TDF) and emtricitabine (FTC) along with a third agent to treat HIV-positive adults. However, other treatment options, including the use of abacavir (ABC) and lamivudine (3TC) when used with ritonavir-boosted darunavir (DRV/r), have rarely been studied. OBJECTIVE: We evaluated the safety and efficacy of the coformulation of ABC/3TC administered with DRV/r in treatment-naïve and treatment-experienced patients. METHODS: HIV-infected adults who received an open-label combination of ABC/3TC/ DRV/r were followed in a community clinic in Montréal. Patients had no resistance to any of the compounds in their regimen. Viral load (VL), CD4 cell count, AST, ALT, and creatinine levels were examined throughout the 48 weeks of follow-up. RESULTS: Sixty-seven patients with a mean age of 45 years were enrolled. Two did not return for follow-up and were excluded. Thirty-five (52%) were treatment- experienced and the remaining were treatment-naïve. HLA-B*5701 test results were available for 56 patients and none were positive. At baseline, mean VL was 4.8 log for treatment-naïve and 2.3 log for experienced patients. Twelve patients discontinued the study regimen prior to reaching the endpoint. At week 48, 79% had a VL <50. Median CD4 cell gain was higher among treatment-naïve patients (273 cells) than among treatment-experienced patients (102 cells) (P = .002). No patient experienced any grade 2 or higher liver enzyme elevation throughout the study. CONCLUSIONS: The new combination of ABC/3TC/DRV/r demonstrates a high rate of antiviral activity with no major toxicity. The drug combination appears to be generally safe and well tolerated.

Relative contribution of HIV-specific functional lymphocyte subsets restricted by protective and non-protective HLA alleles.

Expression of major histocompatibility complex (MHC) class I alleles such as B*57 and B*27 are associated with slow HIV disease progression. HIV-specific immune responses in slow progressors (SP) are characterized by a poly-functional profile. We previously observed within infected subjects that HIV peptide-specific responses could differ from each other in their functional composition. We investigate here whether responses restricted by MHC class I alleles associated with slow disease progression have a more poly-functional profile than responses restricted by other alleles. We stimulated peripheral blood mononuclear cells (PBMCs) isolated from 36 chronically HIV-infected individuals with a panel of optimal peptides restricted by the HLA alleles expressed by each subject, and assessed the contribution of single IL-2-, single IFN-γ-, and IFN-γ/IL-2-secreting lymphocytes to the total response measured using a dual color ELISPOT assay. The contribution of functional subsets to responses restricted by HLA B*57/B*27 was similar in SP and progressors. For responses restricted by other MHC class I alleles, dual IFN-γ/IL-2-secreting lymphocytes contributed significantly more to the total response in SP than progressors. Within SP subjects, peptides restricted by both B*57/B*27 and other alleles stimulated responses with similar functional profiles. In progressors, peptides restricted by B*57/B*27 stimulated responses composed of a significantly greater proportion of IFN-γ/IL-2-secreting cells than peptides restricted by other alleles. Within progressors, the contribution of IFN-γ/IL-2-secreting lymphocytes was greater to epitopes restricted by protective HLA alleles compared with responses restricted by other alleles. HLA haplotypes influence the relative functional composition of HIV-specific responses.