Search

Aim of this study is to assess the impact of doravirine (DOR)-based regimens on cardiovascular risk in treatment-experienced people living with HIV (PLWHIV). We retrospectively analyzed a cohort of 40 treatment-experienced PLWHIV switching to a DOR-based three-drug regimen, evaluating 10-year risk of manifesting clinical cardiovascular diseases (CD) through the Framingham Risk Score at baseline, 12, and 24 weeks of follow-up. At baseline, median predicted 10-year risk of cardiovascular disease (10Y-CD) was 8.0% (interquartile range 4.0-13.0). After 12 weeks, we observed a significant reduction in 10Y-CD (mean decrease -2.21, p  = .012); similarly, we observed a nonsignificant reduction at week 24 ( p  = .336). Regarding metabolic parameters, after 24 weeks we observed a significant reduction in total cholesterol (median change -8.8 mg/dL, p  = .018), low-density lipoprotein cholesterol (median -9.5 mg/dL, p  = .007), and triglycerides (median -19.8 mg/dL, p  < .001). Our results show a favorable metabolic impact of DOR-based regimens along with a promising reduction in 10-year risk of cardiovascular disease.

We tried to investigate and compare the safety of a dual therapy (DT) with dolutegravir+lamivudine (DTG +3TC) versus bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). We performed a retrospective analysis in a cohort of virologically suppressed HIV+ pts switching to DT or BIC in our center. Primary endpoint was to evaluate time to treatment discontinuation (TD) for any cause. Survival analysis was employed to determine time to TD and its predictors were analyzed by Cox regression. Moreover, we collected viro-immunological parameters as well as markers of renal function and lipid profile at baseline and after 24 weeks and assessed changes through nonparametric tests. We analyzed 476 patients: 350 starting a DT and 126 starting BIC. Overall, we registered 21 TD: 15 in the DT group during 170 patient-years of follow-up (PYFU) (a rate of 8.8 per 100 PYFU) and 6 in the BIC one during 48 PYFU (12.5 per 100 PYFU). Estimated probabilities of maintaining study regimen after 24 weeks were 95.5% [standard deviation (SD) ±1.1] in the DT group and 94.9% (SD ±2.0) in the BIC group, with no significant differences between them (log-rank p  = .639). Concerning metabolic profile, in the DT group, after 24 weeks, triglycerides decreased significantly (median change -14 mg/dL, p  < .001), whereas high-density lipoprotein cholesterol increased (+3 mg/dL, p  = .031). In the BIC group, meanwhile, we observed a significant decrease in low-density lipoprotein cholesterol after 24 weeks (-13 mg/dL, p  = .026). Both optimization strategies showed high tolerability in the short term in experienced pts, with few differences between them. Further studies are needed to properly assess the matter.

The GEMINI trials have showed that the two drugs regimen of dolutegravir+lamivudine (DTG +3TC) was noninferior to a three-drug regimen as a first line regimen for treatment-naive people living with HIV. The aim of our study was to confirm, in a real-life setting, the efficacy of this regimen. We conducted a retrospective, observational study enrolling treatment-naive patients starting a first-line regimen with lamivudine plus dolutegravir. We evaluated the virological efficacy and the immunological and metabolic profiles. Changes from baseline were evaluated through linear-mixed models for repeated measures. Linear regression analyses were performed to explore variables associated to significant changes in laboratory parameters. We analyzed a total of 20 patients: 15 (75%) were men with a median age of 34.5 years. During a cumulative time of 15.4 patients years of follow up (PYFU), we did not observe any adverse event or treatment discontinuation and all patients achieved virological suppression in the first 6 months from treatment initiation. Increase in CD4 + cells was significant at both week 24 ( p  = .003) and week 48 ( p  = .007) of follow-up. Moreover, CD4/CD8 ratio also significantly improved [median increase of +0.22 ( p  = .028) after 48 weeks of follow-up]. As to metabolic parameters, we observed no significant changes in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. In a subgroup of 11 patients, we further investigate HIV-1 DNA variations. Our results are in line with the findings of the GEMINI trials, confirming the efficacy and safety of DTG +3TC in treatment-naive patients.

Currently approved 2-drug therapies are as effective as 3-drug regimens but could potentially lead to increased cancer risk due to less efficient immune recovery. We conducted a longitudinal cohort study in a tertiary Italian hospital to investigate HIV+ patients starting a triple therapy (TT) (2 NRTIs +3rd agent) or a dual therapy (DT) (3TC/FTC+boosted-PI, boosted-DRV+RAL, and 3TC/FTC or RPV+DTG) regimen between 2009 and 2018. The effect of DT (vs. TT) on tumor onset was evaluated by the multivariable Cox regression and the marginal structural Cox model, after estimating the inverse probability of treatment weights (IPTW). One thousand one hundred and seven patients who had a median follow-up of 4.2 person-years (py) were evaluated; 69.2% were males, with a median age of 43 years. Overall 2,513 treatments were started during the study period (479 DT, 2,034 TT). Eight tumors occurred over 965 py with DT and 35 over 3,817 py during TT ( p  = .797). In the Cox regression, DT did not predict an increased risk of tumor compared with TT (HR 1.14; p  = .757) after adjusting for potential confounders. A marginal structural model using IPTW (HR 0.68; p  = .328) and stabilized IPTW (HR 0.69; p  = .361) confirmed this result. Preliminary findings from our cohort do not suggest an increased risk of tumors with DT compared to TT.