Background Frailty is associated with mortality and morbidity in the general geriatric population, but less is known about its impact among the aging but generally younger population with human immunodeficiency virus (HIV). Methods The impact of frailty on all-cause mortality during 6 years of follow-up and incident comorbidity during 4 years of follow-up was assessed among 598 HIV-positive and 550 comparable HIV-negative participants aged ≥ 45 years of the AGEhIV Cohort Study. Frailty encompasses 5 domains; weight loss, low physical activity, exhaustion, decreased grip strength, and slow gait speed. Presence of ≥ 3 denotes frailty, 1–2 prefrailty, and 0 robust. Multivariable Cox and logistic regression models were used to assess the independent relationships of frailty with both outcomes, adjusting for HIV infection and traditional risk factors. Results At baseline, 7.5% (n = 86) of participants were frail. During follow-up, 38 participants died. Mortality rate was significantly higher among frail participants: 25.7/1000 person-years of follow-up (PYFU) (95% confidence interval [CI], 14.2–46.4) compared with prefrail (7.2/1000 PYFU [95% CI, 4.7–11.2]) and robust (2.3/1000 PYFU [95% CI, 1.1–4.9]). In fully adjusted analyses, frailty remained strongly associated with death (hazard ratio, 4.6 [95% CI, 1.7–12.5]) and incident comorbidity (odds ratio, 1.9 [95% CI, 1.1–3.1]). No interactions were observed between frailty and HIV status in all analyses. Conclusions Frailty is a strong predictor of both mortality and incident comorbidity independent from other risk factors. Clinical Trials Registration NCT01466582.

BackgroundThe aims of this study were to identify common patterns of comorbidities observed in people living with HIV (PLWH), using a data-driven approach, and evaluate associations between patterns identified.MethodsA wide range of comorbidities were assessed in PLWH participating in 2 independent cohorts (POPPY: UK/Ireland; AGEhIV: Netherlands). The presence/absence of each comorbidity was determined using a mix of self-reported medical history, concomitant medications, health care resource use, and laboratory parameters. Principal component analysis (PCA) based on Somers’ D statistic was applied to identify patterns of comorbidities.ResultsPCA identified 6 patterns among the 1073 POPPY PLWH (85.2% male; median age [interquartile range {IQR}], 52 [47–59] years): cardiovascular diseases (CVDs), sexually transmitted diseases (STDs), mental health problems, cancers, metabolic disorders, chest/other infections. The CVDs pattern was positively associated with cancer (r = .32), metabolic disorder (r = .38), mental health (r = .16), and chest/other infection (r = .17) patterns (all P < .001). The mental health pattern was correlated with all the other patterns (in particular cancers: r = .20; chest/other infections: r = .27; both P < .001). In the 598 AGEhIV PLWH (87.6% male; median age [IQR], 53 [48–59] years), 6 patterns were identified: CVDs, chest/liver, HIV/AIDS events, mental health/neurological problems, STDs, and general health. The general health pattern was correlated with all the other patterns (in particular CVDs: r = .14; chest/liver: r = .15; HIV/AIDS events: r = .31; all P < .001), except STDs (r = –.02; P = .64).ConclusionsComorbidities in PLWH tend to occur in nonrandom patterns, reflecting known pathological mechanisms and shared risk factors, but also suggesting potential previously unknown mechanisms. Their identification may assist in adequately addressing the pathophysiology of increasingly prevalent multimorbidity in PLWH.

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BackgroundThe AGE h IV cohort study is a prospective cohort study evaluating the occurrence of age-related comorbidities in people living with and without HIV. We previously reported a lower forced vital capacity (FVC) in HIV-positive compared with HIV-negative participants in those without heavy smoking exposure at time of enrolment in the AGE h IV cohort study. In this study we evaluate longitudinal changes in spirometry indices in the same AGE h IV cohort accounting for smoking behaviour and other risk factors.Methods We obtained pre-bronchodilator spirometry measurements in AGE h IV cohort participants during biennial visits over a median of 5•9 years (IQR 5•7-6•0). Adjusted declines in forced expiratory volume in 1 s (FEV 1 ), FVC, and FEV 1 /FVC ratio were modelled using linear mixed-effects models and compared by HIV status and smoking status. To evaluate whether changes in spirometry measurements could be driven by increased levels of chronic inflammation, we assessed associations between rates of FEV 1 and FVC decline and CD4 and CD8 T-cell counts, and plasma concentrations of C-reactive protein (CRP), interleukin 6, soluble CD14, soluble CD163, and intestinal fatty-acidbinding protein in separate models. The study is registered at ClinicalTrials.gov, NCT01466582.Findings 500 HIV-positive and 481 HIV-negative participants were included with spirometry data from Oct 29, 2010, to Aug 14, 2018. HIV-positive participants were virally suppressed (<40 copies per mL) during 1627 (95%) study visits, and 159 (32%) HIV-positive and 183 (38%) HIV-negative participants had never smoked. Adjusted declines in FEV 1 were 10•0 mL per year faster in HIV-positive non-smokers (95% CI 4•2 to 15•7, p=0•00066) compared with HIV-negative non-smokers, and 11•1 mL per year faster in HIV-positive smokers (95% CI 0•7 to 21•4, p=0•036) compared with HIV-negative smokers. In comparison, smoking was associated with a 16•4 mL per year steeper decline in FEV 1 among HIV-positive participants (95% CI 8•0 to 24•7, p=0•00012), and 15•3 mL per year steeper decline among HIV-negative participants (95% CI 6•7-24•0, p=0•00052) compared with not smoking. Adjusted yearly declines in FEV₁ and FVC, but not FEV₁/FVC, were significantly greater in HIV-positive than HIVnegative participants overall (additional decline in HIV-positive participants, FEV₁ 10•5 mL per year [95% CI 4•7 to 16•3], p=0•00040; FVC 11•5 mL per year [2•8 to 20•3], p=0•0096; FEV₁/FVC 0•07% per year [-0•05 to 0•19], p=0•26), with a similar observation for never-smokers (FEV₁ 6•0 mL per year [-1•8 to 13•7], p=0•13; FVC 9•1 mL per year [-3•0 to 21•1], p=0•14; FEV 1 /FVC ratio 0•00% per year [-0•18 to -0•18], p=0•97). Higher CRP concentrations during follow-up were associated with accelerated declines in FEV 1 and FVC among HIV-positive participants but not among HIV-negative participants.Interpretation Treated HIV infection was associated with faster declines in both FEV 1 and FVC, but not in the FEV 1 /FVC ratio. These changes were independent of smoking and might have been drive...

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Background We determined the frequency of and factors associated with ≥10% weight gain and its metabolic effects in virally suppressed people with HIV (PWH) from the Dutch national ATHENA cohort switching to TAF and/or INSTI. Methods We identified ART-experienced, but TAF/INSTI-naïve PWH, who switched to a TAF and/or INSTI-containing regimen whilst virally suppressed for &gt;12 months. Individuals with comorbidities/co-medication associated with weight change were excluded. Analyses were stratified by switch to only TAF, only INSTI or combined TAF + INSTI. Factors associated with ≥10% weight gain were assessed using parametric survival models. Changes in glucose, lipids and blood pressure post-switch were modelled using mixed-effect linear regression and compared between those with and without ≥10% weight gain. Results Among 1,544 PWH who switched to only TAF, 2,629 to only INSTI and 918 to combined TAF + INSTI, ≥10% weight gain was observed in 8.8%, 10.6% and 14.4%, respectively. Across these groups, weight gain was more frequent in Western and Sub-Saharan African females than Western males. Weight gain was also more frequent in those with weight loss ≥1 kg/yr before switching, age &lt; 40 years, and those discontinuing efavirenz. In those with ≥10% weight gain, 53.7% remained in the same BMI category, whilst a BMI change from normal/overweight at baseline to obesity at 24 months post-switch was seen in 13.9%, 11.7% and 15.2% of those switching to only TAF, only INSTI and combined TAF + INSTI respectively. PWH with ≥10% weight gain showed significantly larger, but small increases in glucose, blood pressure and lipid levels. Lipid increases were limited to those whose switch included TAF, whereas lipids decreased after switching to only INSTI. Conclusions Weight gain of ≥10% after switch to TAF and/or INSTI was common in virally suppressed PWH, particularly in females and those starting both drugs simultaneously. Consequent changes in metabolic parameters were however modest.

Background We previously reported T-cell senescence to be similar in people with human immunodeficiency virus (PWH) with suppressed viremia (predominantly men who have sex with men [MSM]) and human immunodeficiency virus (HIV)-negative otherwise comparable controls but greater than in healthy blood donors. This led us to compare CD4+ and CD8+ T-cell counts and CD4+/CD8+ ratios between HIV-negative MSM and men who only have sex with women (MSW) and relate observed differences in behavioral factors and infectious exposures, including cytomegalovirus (CMV) infection. Methods In 368 HIV-negative MSM and 72 HIV-negative MSW, T lymphocyte phenotyping was performed 3 times biennially. Baseline CMV serology and sexually transmitted infection (STI) incidence and/or STI seroprevalence, sexual, and substance-use behavior data were collected during study visits. Results Men who have sex with men, compared with MSW, had higher CD8+ counts (551 vs 437 cells/mm3, P &lt; .001), similar CD4+ counts (864 vs 880 cells/mm3, P = .5), and lower CD4+/CD8+ ratios (1.84 vs 2.47, P &lt; .001). Differences were most pronounced for MSM with &gt;10 recent sex partners and partly explained by higher CMV seroprevalence in MSM. Conclusions These findings suggest that factors other than HIV may, in both PWH and certain HIV-negative MSM, contribute to a low CD4+/CD8+ ratio. Whether this, like in PWH, contributes to comorbidity risk in HIV-negative MSM requires further study.

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