Introduction Adipose tissue (AT) alterations are common in people living with HIV (PLWH). Decreases in AT density suggest disrupted adipocyte function/hypertrophy. We assessed changes in AT density after antiretroviral therapy (ART) initiation and associations with immuno-metabolic parameters. Methods In a prospective randomized clinical trial of ART initiation, L4-L5 abdominal CT scans measured subcutaneous (SAT) and visceral (VAT) AT area and density in treatment-naïve PLWH randomized to tenofovir-emtricitabine plus atazanavir-ritonavir, darunavir-ritonavir, or raltegravir. Linear regression models compared weeks 0 (W0) and 96 (W96) levels, and 96-week changes, in SAT and VAT density (in Hounsfield units, HU). Spearman’s correlations assessed relationships between AT density and immuno-metabolic parameters. Results Participants (n=228) were 89% male and 44% white non-Hispanic. Median age was 36 years, baseline HIV-1 RNA 4.6 log10 copies/mL, and CD4+ T cell count 344 cells/mm3. Over 96 weeks, SAT and VAT HU decreased significantly in all arms. Less dense W96 SAT and VAT density correlated with higher HDL cholesterol and adiponectin (r=0.19 to 0.30) levels and lower IL-6, non-HDL cholesterol, triglyceride, leptin and HOMA-IR (r=-0.23 to -0.68) levels at W96 after adjusting for baseline CD4+ T cell count, HIV-1 RNA and baseline AT area. Conclusions Following virologic suppression, lower SAT and VAT density was associated with greater plasma measures of systemic inflammation, lipid disturbances and insulin resistance independent of AT area, suggesting changes in AT density with ART may lead to adverse health outcomes independent of AT quantity.

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Background:The AIDS Clinical Trials Group study A5353 demonstrated the efficacy and safety of dolutegravir and lamivudine for initial treatment of HIV-1 infection at week 24 in individuals with HIV-1 RNA 1000-500 000 copies/mL. Optimal ART for treatment-naive individuals must be durable. Objectives:The aim of this study was to estimate the efficacy and safety of dolutegravir plus lamivudine at week 48 and compare the efficacy in participants with baseline HIV-1 RNA 100 000 copies/mL versus .100 000 copies/mL. Methods: Virological success was defined as HIV-1 RNA ,50 copies/mL by FDA Snapshot criteria. Definition of virological failure included confirmed HIV-1 RNA .200 copies/mL at week 24 or later. The proportion of participants with virological success was estimated using two-sided exact Clopper-Pearson 95% CI. Comparison between screening HIV-1 RNA (100 000 versus .100 000 copies/mL) strata was carried out by Fisher's exact test. The study was registered with ClinicalTrials.gov, number NCT02582684.Results: A total of 120 enrolled eligible participants were included in the analysis. At week 48, 102 of the 120 participants (85%; 95% CI 77%-91%) had virological success. Virological success was similar between screening HIV-1 RNA groups. Six (5%) participants had virological non-success and one additional participant experienced virological failure while on study but off study treatment. No new drug resistance mutations were observed. Six (5%) participants had study-related grade 3 or higher adverse events and none discontinued study treatment.Conclusions: These results add to the evidence that dolutegravir plus lamivudine is a safe and effective option for initial ART in individuals with HIV-1 RNA ,500 000 copies/mL.

Background:We have previously shown that the initiation of antiretroviral therapy (ART) is associated with a decrease in skeletal muscle density (greater fat accumulation), suggesting that gains in lean body mass seen in many ART studies may reflect gains in low quality, fatty muscle. Here, we explore whether skeletal muscle density and area are associated with markers of inflammation and immune activation.Methods: ART-naïve people with HIV were randomized to raltegravir or ritonavir-boosted atazanavir or darunavir, each with tenofovir disoproxil fumarate/emtricitabine. Abdominal computed tomography scans from baseline and week 96 were reanalyzed for psoas density and area and correlations explored with inflammation [interleukin-6 (IL-6) and high-sensitivity C-reactive protein] and immune activation [soluble CD14 (sCD14), soluble CD163 (sCD163), and %CD38 + HLADR + on CD4 + or CD8 + T cells].Results: Two hundred twenty-two participants had available inflammation/immune activation markers and paired computed tomog-raphy scans. At baseline, lower psoas density (greater fat) correlated with higher IL-6 (r = 20.26, P , 0.001) and sCD163 (r 20.15, P = 0.03) and lower lean psoas area correlated with higher IL-6, highsensitivity C-reactive protein, sCD14, sCD163, and %CD38 + HLADR + on CD4 + T cells (r = 20.30-0.13; all P # 0.05). From baseline to week 96, greater percent decrease in total psoas density (more fat) correlated with greater increase in IL-6 (r = 20.14; P = 0.04); greater % decrease in lean psoas area correlated greater increases in IL-6, sCD14, sCD163, and %CD38 + HLADR + on CD8 + T cells (r = 20.15 to 20.18; all P , 0.04).Conclusions: Greater fat infiltration within the psoas muscle (lower density) and greater loss in lean psoas muscle area were associated with higher inflammation and immune activation, which may portend important effects on muscle function and cardiometabolic risk.

Background SAB-185, a novel fully-human IgG polyclonal immunoglobulin product, underwent phase 2 evaluation for non-hospitalized adults with mild-moderate COVID-19. Methods Participants received intravenous SAB-185 3,840 units/kg (low-dose) or placebo, or 10,240 units/kg (high-dose) or placebo. Primary outcome measures were nasopharyngeal SARS-CoV-2 RNA <lower limit of quantification (LLoQ) at study days 3, 7, and 14, time to symptomatic improvement, and safety through day 28. Results Two-hundred thirteen participants received low-dose SAB-185/placebo (n=107/106) and 215 high-dose SAB-185/placebo (n=110/105). The proportions with SARS-CoV-2 RNA <LLoQ were higher for SAB-185 versus placebo at days 3 and 7 and similar at day 14, and significantly higher at day 7 for high-dose SAB versus placebo only, relative risk (95% CI) 1.23 (1.01, 1.49). At day 3, SARS-CoV-2 RNA levels were lower with low-dose and high-dose SAB-185 versus placebo, differences in medians of -0.78 log10copies/mL (p=0.08) and -0.71 log10copies/mL (p=0.10), respectively. No difference was observed in time to symptom improvement: median 11/10 days (p=0.24) for low-dose SAB-185/placebo and 8/10 days (p=0.50) for high-dose SAB-185/placebo. Grade ≥3 adverse events occurred in 5%/13% of low-dose SAB-185/placebo and 9%/12% of high-dose SAB-185/placebo. Conclusions SAB-185 was safe and generally well tolerated and demonstrated modest antiviral activity in predominantly low-risk non-hospitalized adults with COVID-19.