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Control of viral replication to below the level of quantification using combination antiretroviral therapy (ART) [cART] has led to a dramatic fall in mortality and morbidity from AIDS. However, despite the success of cART, it has become apparent that many patients do not achieve normalized CD4+ T-cell counts despite virological suppression to below the level of quantification (<50 copies/mL). Increasing data from cohort studies and limited data from clinical trials, such as the SMART study, have shown that higher CD4+ T-cell counts are associated with reductions in morbidity and mortality from both AIDS and serious non-AIDS (SNA) conditions, including cardiovascular disease. Enhancement of immune restoration over and above that achievable with ART alone, using a number of strategies including cytokine therapy, has been of interest for many years. The most studied cytokine in this setting is recombinant interleukin (IL)-2 (rIL-2). The purpose of this review is to describe the current status of rIL-2 as a therapeutic agent in the treatment of HIV-1 infection. The review focuses on the rationale underpinning the exploration of rIL-2 in HIV infection, summarizing the phase II and III findings of rIL-2 as an adjunctive therapy to ART and the phase II studies of rIL-2 as an antiretroviral-sparing agent. The phase II studies demonstrated the potential utility of continuous intravenous IL-2 and subsequently intermittent dosing with subcutaneous rIL-2 as a cytokine that could expand the CD4+ T-cell pool in HIV-1-infected patients without any significant detrimental effect on HIV viral load and with an acceptable adverse-effect profile. These data were utilized in designing the phase II studies of rIL-2 as an ART-sparing agent and, more importantly, the large phase III clinical endpoint studies of rIL-2 in HIV-1-infected adults, ESPRIT and SILCAAT. In the latter, subcutaneous rIL-2 was given intermittently (5 days of twice-daily dosing at 4.5-7.5 million international units per dose every 8 weeks) to HIV-1-infected adults receiving cART using an induction/maintenance strategy. Both studies explored the clinical benefit of intermittent subcutaneous rIL-2 with cART versus cART in HIV-infected adults with CD4+ T-cell counts ≥300 cells/mL (ESPRIT study) and 50-299 cells/μL (SILCAAT study). Both studies showed that receipt of rIL-2 conferred no clinical benefit despite a significantly higher CD4+ T-cell count in the rIL-2 arms of both studies. Moreover, there was an excess of grade 4 clinical events in ESPRIT rIL-2 recipients. The results of the phase III clinical endpoint studies showed that rIL-2 has no place as a therapeutic agent in the treatment of HIV infection. [ABSTRACT FROM AUTHOR]

Background: Hepatic steatosis is a major cause of chronic liver disease associated with several negative health outcomes. We compared the prevalence of and factors associated with steatosis in people living with and without HIV. Methods: Older (>50 years) and younger (<50 years) people with HIV and older HIV‐negative controls (>50 years) underwent liver transient elastography examination with controlled attenuation parameter (steatosis ≥238 dB/m, moderate/severe steatosis ≥280 dB/m, liver fibrosis ≥7.1 kPa). We compared groups using logistic regression/Chi‐squared/Fisher's exact/Kruskal–Wallis tests. Results: In total, 317 participants (109 older people with HIV; 101 younger people with HIV; 107 HIV‐negative controls) were predominantly white (86%) and male (76%), and 21% were living with obesity (body mass index ≥30 kg/m2). Most (97%) people with HIV had undetectable HIV RNA. The prevalence of fibrosis was 8.4%, 3.0%, and 6.5% in the three groups, respectively (p = 0.26). Fibrosis was predominately (>65%) mild. The prevalence of steatosis was the same in older people with HIV (66.4%) and controls (66.4%) but lower in younger people with HIV (37.4%; p < 0.001). After adjustment, younger people with HIV were less likely to have steatosis (odds ratio [OR] 0.26; 95% confidence interval [CI] 0.14–0.52) than controls, but male sex (OR 2.45; 95% CI 1.20–4.50) and high waist‐to‐hip ratio (OR 3.04; 95% CI 1.74–5.33) were associated with an increased odds of steatosis. We found no association between steatosis and HIV‐related variables. Conclusions: The prevalence of hepatic steatosis and fibrosis was similar between older participants regardless of HIV status. Age, sex, and abdominal obesity, but not HIV‐related variables, were associated with steatosis. Interventions for controlling obesity should be integrated into routine HIV care. [ABSTRACT FROM AUTHOR]

Objectives: Integrase strand transfer inhibitors (INSTIs) are commonplace in modern antiretroviral therapy (ART). Increased weight gain with their use is increasingly scrutinized. We evaluated weight changes in treatment‐naïve adults with HIV‐1 attending a UK centre who started regimens including raltegravir or dolutegravir. Methods: A retrospective cohort study of adults prescribed an INSTI between January 2015 and March 2020 were categorized as having started an ART regimen containing raltegravir, dolutegravir, a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor. Individuals with one or more weight measurement ≤ 5 years both pre‐ and post‐ART initiation, who started a three‐drug regimen with ≥ 6 months duration and achieved virological suppression (< 50 copies/mL) within 6 months were included. A random effects model with linear slope pre‐ and post‐ART was used, adjusting for age, gender, ethnicity, ART regimen, backbone and year of initiation. Results: The cohort included 390 adults; 88.7% were male, 66.4% were of white ethnicity, their median age was 40 years, there was a median of six weight measurements, 2.2 years from diagnosis to ART initiation, 2.9 years from ART to the last weight measurement, and weight and body mass index at initiation were 75 kg and 24.1 kg/m2 respectively. Of these, 254 (65%) started an INSTI. The average pre‐ART rate of weight gain was 0.44 kg/year [95% confidence interval (CI): 0.19–0.70], increasing to 0.88 kg/year (0.63–1.10, p = 0.04) after ART initiation. Our adjusted model found no evidence of an association between ART regimen and rate of weight gain. Conclusions: Weight increased in the cohort both pre‐ and post‐ART. We found no evidence of a higher rate of weight gain following ART initiation with an INSTI compared with other regimens. [ABSTRACT FROM AUTHOR]