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[Objectives] To evaluate the efficacy and safety of the two-pill regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat as a switching strategy in heavily treatment-experienced people living with HIV (PLWH)., [Methods] Multicentre, prospective, single-arm pilot clinical trial. Participants were virologically suppressed adults receiving a stable antiretroviral regimen of at least three pills from at least three drug families due to previous virological failures and/or toxicities with no documented resistance to integrase strand transfer inhibitors or darunavir (≥15 points, Stanford). Clinical and laboratory assessments were performed at 0, 4, 12, 24, 36 and 48 weeks. HIV-1 proviral DNA was amplified and sequenced by Illumina at baseline. Plasma bictegravir concentrations were determined in 22 patients using UHPLC-MS/MS. The primary study endpoint was viral load (VL)< 50 copies/mL at Week 48 (ITT)., [Results] We enrolled 63 participants (92% men) with median baseline CD4 count of 515 cells/mm3 (IQR: 334.5–734.5), 24 years on ART (IQR: 15.9–27.8). The median number of pills was 4 (range: 3–10). At baseline, proviral DNA was amplified in 39 participants: 33/39 had resistance mutations. Three participants discontinued owing to toxicity. At 48 weeks, 95% had VL < 50 copies/mL by ITT and 100% by PP analysis. A modest increase was observed in the bictegravir plasma concentration, and a significant decrease in estimated glomerular filtration rate was observed only at Week 4, probably related to interaction with renal transporters., [Conclusions] Our data suggest that BIC/FTC/TAF + darunavir/cobicistat is an effective, well-tolerated regimen that may improve convenience and, potentially, long-term success in stable heavily pre-treated PLWH.

[Background] Few women have been included in darunavir/cobicistat clinical development studies, and hardly any of them were antiretroviral experienced or treated with anything other than triple-based therapies., [Objectives] Our aim was to increase our knowledge about women living with HIV undergoing darunavir/cobicistat-based regimens., [Methods] A multicentre (21 hospitals), retrospective study including a centrally selected random sample of HIV-1 patients starting a darunavir/cobicistat-based regimen from June 2014 to March 2017 was planned. Baseline characteristics, 24 and 48 week viral load response (<50 copies/mL), CD4+ lymphocyte count increase, time to change darunavir/cobicistat and adverse event occurrence were all compared by sex. The study was approved by each of the 21 ethics committees, and patients signed informed consent., [Results] Out of 761 participants, 193 were women. Similar characteristics were found for both sexes, except that the women had a longer duration of HIV infection (P = 0.001), and were less frequently pre-treated with darunavir/cobicistat in their previous regimen (P = 0.02). The main reason for using a darunavir/cobicistat-based regimen was simplification, without differences by sex, while monotherapy seems to be more frequently prescribed in women than in men (P = 0.067). The main outcomes, HIV viral load response, CD4+ lymphocyte count increase at 24 or 48 weeks, occurrence of adverse events, main reasons for changing and time to the modify darunavir/cobicistat regimen, did not show differences between the sexes., [Conclusions] No sex disparities were found in the main study outcomes. These results support the use of a darunavir/cobicistat-based regimen in long-term pre-treated women. Clinical Trial.gov No. NCT03042390.

[Background] Late HIV diagnosis remains one of the challenges in combating the epidemic. Primary care providers play an important role in screening for HIV infection. Our study aims to evaluate the relationship between knowledge and barriers to HIV testing and screening outcomes. The impact of an education program for primary care providers, towards improving HIV testing and late diagnosis rates, is also assessed., [Methods] A self-administered questionnaire that was developed within the framework of the European project OptTEST was used to examine HIV knowledge and barriers to HIV testing scores before and after being involved in an HIV education program. A quasi-experimental design with pre- and post-intervention measures was performed to investigate its impact. We performed multivariable logistic regression analysis to assess the relationship between variables for the HIV testing offer., [Results] A total of 20 primary care centers and 454 primary care staff were included. Baseline OptTEST results showed that more knowledgeable staff offered an HIV test more frequently (OR 1.07; CI 95% 1.01–1.13; p = 0.027) and had lower barrier scores (OR 0.89; CI 95% 0.77–0.95; p = 0.005). Nurses had lower scores in knowledge-related items (OR 0.28; CI 95% 0.17–0.46; p<0.001), but higher scores in barrier-related items than physicians (OR 3.28; CI 95% 2.01–5.46; p<0.001). Specific centers with more knowledgeable staff members had a significant association with a greater level of new HIV diagnosis rates (OR 1.61; CI 95% 1.04–2.49; p = 0.032). After the intervention, we found that 12 out of 14 individual questions showed improved scores. In the 6 months after the training program, we similarly found a higher HIV testing rate (OR 1.19; CI 1.02–1.42; p = 0.036)., [Conclusions] This study highlights the association between knowledge and barriers to HIV testing, including HIV testing rates. It shows that it is possible to modify knowledge and reduce perceived barriers through educational programs, subsequently improving HIV screening outcomes.

[Background & Aims] Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where sofosbuvir/velpatasvir/voxilaprevir may not be available., [Methods] GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response (SVR) at 12 weeks after treatment completion (SVR12) was recorded., [Results] A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) were studied. After a resistance report, 186 patients were retreated. An SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin., [Conclusions] In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited., [Lay summary] Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations.