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Objective Large inter-individual variability in the pharmacokinetics of rilpivirine and cabotegravir has been reported in the first weeks after starting long-acting injectable (LAI) therapy. Here, we assessed the distribution of rilpivirine and cabotegravir trough concentrations in people with HIV (PWH) on long-term LAI treatment. Methods Adult PWH treated with LAI for at least 32 weeks with an assessment of drug plasma trough concentrations were considered. The proportion of rilpivirine and cabotegravir plasma trough concentrations below four-times the protein-adjusted concentrations required for 90% inhibition of viral replication (4×PA-IC90) was estimated. Results Sixty-seven PWH were identified. LAI treatment duration was 216 ± 80 weeks (range 32–320 weeks). Cabotegravir concentrations were associated with lower inter-individual variability compared with rilpivirine (45% versus 84%; P  < 0.05). No differences were found in rilpivirine (160 ± 118 versus 189 ± 81 ng/mL; P  = 0.430) and cabotegravir (1758 ± 807 versus 1969 ± 802 ng/mL; P  = 0.416) trough concentrations in males (n  = 55) versus females (n  = 12). A non-significant trend for lower cabotegravir concentrations was found in PWH with a body mass index >30 kg/m2 (n  = 9) versus non-obese participants (1916 ± 905 versus 1606 ± 576 ng/mL; P  = 0.131). Three out of the 67 PWH had at least one drug concentration <4×PA-IC90: 100% of PWH had undetectable HIV viral load. Conclusions At steady state, optimal systemic exposure of cabotegravir and rilpivirine was found in most PWH; cabotegravir trough concentrations were associated with lower inter-individual variability compared with rilpivirine. The study was not powered to assess the contribution of sex and/or body weight on LAI exposure due to the small number of females and obese PWH included. [ABSTRACT FROM AUTHOR]

This article discusses the use of fostemsavir, a first-in-class attachment inhibitor, to overcome potential drug-drug interactions (pDDIs) between chemotherapy and boosted protease inhibitors (bPIs) in heavily treatment-experienced people with HIV (PWH) and cancer. The authors present two cases of PWH with solid malignancies who were able to undergo first-line chemotherapy with the use of fostemsavir to avoid pDDIs. The authors suggest that fostemsavir provides an additional option for constructing a suppressive antiretroviral regimen in PWH with cancer, but caution that strict virological monitoring is necessary. They also mention the potential for fostemsavir to increase the exposure of paclitaxel, a chemotherapy drug, and advise clinicians to monitor for potential paclitaxel-related toxicity in PWH treated with fostemsavir. [Extracted from the article]

• A mortality gap remains for late presenters, particularly, AIDS presenters, in recent years. • Increased mortality for AIDS presenters was driven by AIDS events in the first year. • Two-year immune recovery is the key for long-term mortality in short-term AIDS survivors. • Late and AIDS presenters still show a higher risk treatment failure. • Urgent public health strategies are needed for emerging unknown HIV infections. Limited data are available on the long-term outcomes in recent years for late HIV diagnosis (LD). All subjects with HIV enrolled in the ICONA cohort in 2009-2022 who started antiretroviral treatment (ART) within 4 months from diagnosis were included and divided into: (i) pre-ART CD4 count ≥350/mm3 without AIDS (non-LD), (ii) pre-ART CD4 count <350/mm3 without AIDS (LD asymptomatic), and (iii) with AIDS events pre-ART (LD-AIDS). The estimated probability and independent risk for mortality (all-cause and cause-specific) and treatment failure were evaluated. Of 6813 participants (2448 non-LD, 3198 LD asymptomatic, and 1167 LD-AIDS), 161 (2.4%) died after ART initiation. At survival analysis, a higher probability of all-cause mortality has been identified for LD than non-LD (P <0.001) and within the former, for LD-AIDS over LD asymptomatic (P <0.001). After adjusting for confounders, LD showed a higher risk of all-cause mortality (vs non-LD adjusted hazard ratio (aHR) 5.51, P <0.001) and, in particular, being an AIDS presenter predicted a greater risk of all-cause (aHR = 4.42, P <0.001), AIDS-related (adjusted subhazard ratio [aSHR] = 16.86, P <0.001), and non-AIDS–related mortality (aSHR = 1.74, P = 0.022) than the rest of the late presenters. Among the short-term survivors in the LD-AIDS group, the long-term mortality was mediated by the lack of immune recovery at 2 years. Finally, LD compared with non-LD and, particularly, among the former, LD-AIDS over LD asymptomatic showed a greater risk of treatment failure. In recent years, LD subjects, particularly, AIDS presenters, remained at a higher risk of poorer outcomes. Public health strategies for early HIV diagnosis are urgently needed to constrain the mortality gap. [ABSTRACT FROM AUTHOR]

• Both bictegravir (BIC) and dolutegravir (DTG), in association with emtricitabine/tenofovir alafenamide (FTC/TAF), show high efficacy in treatment-naïve people living with human immunodeficiency virus. • DTG+FTC/TAF discontinuations are mainly due to switching to a single tablet regimen or a two-drug regimen. • Favourable immunological recovery was observed, even in the short term. First-line integrase strand transfer inhibitor-based regimens have become commonly used in clinical practice over the last decade. This study aimed to analyse and compare the efficacy and safety of bictegravir (BIC) and dolutegravir (DTG) when prescribed in association with emtricitabine/tenofovir alafenamide (FTC/TAF) as part of a first-line regimen for the treatment of human immunodeficiency-1 (HIV-1) infection. Treatment-naïve people living with HIV (PLWHIV) starting a first-line regimen with either BIC/FTC/TAF (BIC group) or FTC/TAF+DTG (DTG group) were analysed. Snapshot analyses were performed after 24 and 48 weeks to evaluate virological efficacy. In addition, differences in the rate of treatment discontinuation (TD) between the two groups were evaluated using the Kaplan–Meier method and the log rank test. Data from 327 PLWHIV were analysed: 140 in the DTG group and 187 in the BIC group. At 48 weeks, 90.0% of individuals in the DTG group and 86.7% of those in the BIC group achieved HIV-RNA <50 copies/mL. In total, 88 and 38 cases of TD were observed in the DTG group and BIC group, respectively. The estimated probability of maintaining the study regimen at week 48 was 59.5% in the DTG group and 84.2% in the BIC group. Analysing changes in immunological parameters after 48 weeks, median improvements of +169 cell/mm3 (P <0.001) and +233 cell/mm3 (P <0.001) were observed in the DTG group and the BIC group, respectively. Both BIC and DTG, in combination with FTC/TAF, show promising efficacy and safety as first-line strategies in clinical practice, with favourable immunological recovery even in the short term. [ABSTRACT FROM AUTHOR]