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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]

Enfuvirtide was the first of a new class of antiretroviral agents termed 'fusion inhibitors' used for the treatment of HIV-1 infection. Enfuvirtide is administered subcutaneously and injection site reactions (ISR) are commonplace (98%). The aim of this study was to analyse in detail the histopathological changes associated with striking ISR seen in four patients. Biopsies were obtained at various times post-injection and were reviewed histologically. The changes in epidermal, dermal and subcutaneous connective tissue and the presence and nature of the inflammatory cellular infiltrate were noted. An immunohistochemical assessment was undertaken. All biopsy specimens demonstrated striking changes in the dermal connective tissue. Alteration in collagen was the most prominent feature and resembled a morphoea/scleroderma-like process. These changes persisted well beyond cessation of enfuvirtide (>1 year). The relative populations of dermal dendritic cells (DDC) (types 1 (Factor XIIIa) and 2 (CD34+)) were analysed and a reciprocal relationship between DDC subpopulations was observed akin to that observed in other sclerosing and fibrosing conditions. This study details histopathological changes associated with enfuvirtide ISR. We postulate that changes in DDC populations may contribute to the pathogenesis of the sclerotic process observed with enfuvirtide ISR. [ABSTRACT FROM AUTHOR]

Background: Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIV-infected patients do not currently exist. Methods: We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1∶1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer were compared between cases and controls. Results: Cases (n = 72) and controls (n = 72) were 25.7% female, 51.4% black, 65.3% current smokers, 9.7% diabetic, 36.1% co-infected with Hepatitis B/C, and 75.0% were on cART at baseline. Median (IQR) age was 45 (41, 51) years with CD4+ count of 553 (436, 690) cells/mm3. Baseline CC16 and SP-D were similar between cases and controls, but hsCRP was significantly higher in cases than controls (2.94 µg/mL in cases vs. 1.93 µg/mL in controls; p = 0.02). IL-6 and d-dimer levels were also higher in cases compared to controls, though differences were not statistically significant (p-value 0.06 and 0.10, respectively). Conclusions: In patients with cART-treated HIV infection, higher levels of systemic inflammatory markers were associated with increased bacterial pneumonia risk, while two pulmonary-specific inflammatory biomarkers, CC16 and SP-D, were not associated with bacterial pneumonia risk. [ABSTRACT FROM AUTHOR]

Background. Human immunodeficiency virus (HIV) replication and immune activation may increase inflammation and coagulation biomarkers. Limited data exist comparing such biomarkers in persons with and without HIV infection. Methods. For persons 45-76 years of age, levels of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, D-dimer, and cystatin C were compared in 494 HIV-infected individuals in the Strategies for Management of Anti-Retroviral Therapy (SMART) study and 5386 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study. For persons 33-44 years of age, hsCRP and IL-6 levels were compared in 287 participants in the SMART study and 3231 participants in the Coronary Artery Development in Young Adults (CARDIA) study. Results. hsCRP and IL-6 levels were 55% and 62% higher among (P < .001) (P < .001) HIV-infected participants than among CARDIA study participants. Compared with levels noted in MESA study participants, hsCRP, IL-6, D-dimer, and cystatin C levels were 50%, 152%, 94%, and 27% higher, respectively (P < .001, for each), among HIV-infected participants. HIV-infected participants receiving antiretroviral therapy who had HIV RNA levels ⩽400 copies/mL had levels higher (by 21% to 60%) (P < .001) than those in the general population, for all biomarkers. Conclusions. hsCRP, IL-6, D-dimer, and cystatin C levels are elevated in persons with HIV infection and remain so even after HIV RNA levels are suppressed with antiretroviral therapy. Additional research is needed on the pathophysiology of HIV-induced activation of inflammatory and coagulation pathways, to guide potential interventions. [ABSTRACT FROM AUTHOR]