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Objective: To determine whether nucleos(t)ide reverse transcriptase inhibitors (NRTI) contribute to an accelerated loss in telomere length (TL) in HIV-infected patients on antiretroviral therapy (ART). Design: Substudy of randomised controlled trial. Methods: Patients with HIV RNA <50 copies/mL on combination ART (n = 256) were randomised to darunavir/ritonavir (DRV/r) 800/100 mg once daily, either as monotherapy (n = 127) or with 2 NRTIs (n = 129) for up to 144 weeks. TL and telomerase activity was quantified on stored peripheral blood mononuclear cells (PBMC; n = 124) using quantitative real time PCR. Results: Patients in the sub-study had a mean age of 44 years and had received NRTI for a mean of 6.4 years (range 1–20 years). As expected, older patients have significantly shorter TL (p = 0.006), while women had significantly longer TL (p = 0.026). There was no significant association between TL and either the duration of prior NRTI treatment (p = 0.894) or the use of a PI versus NNRTI (p = 0.107). There was no significant difference between patients who continued or ceased NRTI in the mean change/year of TL or telomerase (p = 0.580 and 0.280 respectively). Conclusion: Continuation versus cessation of NRTI treatment was not associated with an accelerated loss in TL or telomerase activity. [ABSTRACT FROM AUTHOR]

Background: In patients receiving combination antiretroviral therapy (ART), switching to monotherapy with ritonavir-boosted darunavir (DRV/r) can maintain plasma HIV-1 RNA suppression with no treatment-emergent drug resistance; effects on cellular HIV-1 DNA burden are less well characterized. Methods: In MONET, patients on stable combination ART for at least 6 months with plasma HIV-1 RNA <50 copies/mL and no history of virologie failure switched to DRV/r 800/100 mg once daily, either alone (n = 127) or with 2 nucleoside reverse transcriptase inhibitors (NRTIs) (n = 129). In a representative subset of 146 patients, total HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) was tested retrospectively at baseline, week 48, week 96, and week 144. Results: Mean HIV-1 DNA levels at baseline vs week 144 were 2.50 vs 2.49 log10 copies/106 PBMC in the monotherapy arm and 2.59 vs 2.61 log10 copies/106 PBMC in the triple therapy arm, with mean (median) changes of -0.05 (-0.03) and +0.03 (+0.01) log10 copies/106 PBMC in the 2 arms, respectively. Overall baseline HIV-1 DNA levels were higher in patients with nadir CD4 counts <200 cell/(μL (P < .05) and in patients who over 144 weeks experienced at least 1 HIV-1 RNA measurement >50 copies/mL (P < .05). Conclusions: In this substudy of the MONET trial, HIV-1 DNA levels remained stable during 144 weeks of either DRV/r monotherapy or triple therapy with DRV/r + 2 NRTIs. In both treatment arms, baseline HIV-1 DNA levels were predicted by the nadir CD4 cell count and predictive of plasma HIV-1 RNA detection during follow-up. [ABSTRACT FROM AUTHOR]

Background: Protease inhibitor monotherapy is an attractive treatment option for HIV-infected subjects. Data assessing neuropsychiatric events with the use of protease inhibitor monotherapy are sparse. Methods: Clinician- and patient-reported neuropsychiatric events were assessed over 48 weeks in HIV-infected subjects on stable antiretroviral therapy, with a plasma HIV RNA <50 copies/mL, randomised to commence on a one to one basis darunavir/ritonavir (800/100 mg once daily) alone (DRVrMono) or with nucleoside analogues (DRVrNRTI). Patient-reported events were assessed by the Functional Assessment of HIV Infection (FAHI) questionnaire and included an assessment of cognitive function. Results: Of 256 subjects enrolled, clinician-reported grade 1–4 adverse events of the nervous system (all cause) were seen in 16% of patients in each treatment arm. FAHI questionnaires were completed by 206 subjects at 48 weeks. No differences in cognitive functioning or other FAHI scores were observed between study treatment groups: Cognitive Functioning score [mean (SD)] 8.9 (2.4) and 9.0 (2.6) in DRVrMono arm and 8.8 (2.6) and 8.9 (2.8) in DRVrNRTI arm at baseline and week 48, respectively (P value for difference = .76). Conclusion: In this exploratory analysis, no differences in the evolution of neuropsychiatric adverse events over 48 weeks are observed in HIV-infected subjects randomised to switch antiretroviral therapy to darunavir/ritonavir with or without nucleoside reverse transcriptase inhibitors. [ABSTRACT FROM AUTHOR]

Background: In low- and middle-income countries (LMICs), a substantial unmet need for affordable single-tablet regimen (STR) options remains. Rilpivirine (RPV, TMC278) is formulated in a low-cost STR with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Objectives: Switching at Low HIV-1 RNA into Fixed Dose Combinations (SALIF) compared RPV with efavirenz (EFV), both as STRs with TDF and FTC, in maintaining virologic suppression. Methods: SALIF was a phase 3b, randomised, open-label, non-inferiority study in virologically suppressed adults (HIV-1 RNA < 50 copies/mL) on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy (ART) in Cameroon, Kenya, Senegal, South Africa, Uganda and Thailand. Patients (N = 426), stratified by NNRTI use, were randomised 1:1 to receive TDF/FTC/RPV (300/200/25 mg qd) or TDF/FTC/EFV (300/200/600 mg qd). Primary endpoint was proportion of patients with virologic suppression (HIV-1 RNA < 400 copies/mL) at week 48 (intent-to-treat, modified Food and Drug Administration Snapshot, 10% non-inferiority margin). Results: Patients received TDF/FTC/RPV (n = 213) or TDF/FTC/EFV (n = 211). At week 48, virologic suppression was maintained in 200/213 (93.9%) patients in the RPV arm and 203/211 (96.2%) in the EFV arm (difference –2.3%; 95% confidence interval: −6.4, +1.8), demonstrating non-inferiority of TDF/FTC/RPV. One patient in each arm experienced virologic failure without treatment-emergent resistance. Twenty-seven patients discontinued prematurely (8.0% RPV vs. 4.7% EFV), the most frequent reasons being adverse events (3.3% vs. 0.5%, respectively), site closure (1.9% vs. 0.5%), loss to follow-up (0.9% vs. 1.4%) and consent withdrawal (0.9% vs. 1.4%). Conclusion: In adults with suppressed viral load on first-line NNRTI-based ART in LMICs, switching to an STR of TDF/FTC/RPV was non-inferior to TDF/FTC/EFV in maintaining high rates of viral suppression with a comparable tolerability profile. [ABSTRACT FROM AUTHOR]