One in 10 Virally Suppressed Persons With HIV in The Netherlands Experiences ≥10% Weight Gain After Switching to Tenofovir Alafenamide and/or Integrase Strand Transfer Inhibitor

Background: We determined the frequency of and factors associated with ≥10% weight gain and its metabolic effects in virally suppressed people with human immunodeficiency virus (PWH) from the Dutch national AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort switching to tenofovir alafenamide (TAF) and/or integrase strand transfer inhibitor (INSTI). Methods: We identified antiretroviral therapy-experienced but TAF/INSTI-naive PWH who switched to a TAF and/or INSTI-containing regimen while virally suppressed for >12 months. Individuals with comorbidities/comedication associated with weight change were excluded. Analyses were stratified by switch to only TAF, only INSTI, or TAF + INSTI. Factors associated with ≥10% weight gain were assessed using parametric survival models. Changes in glucose, lipids, and blood pressure postswitch were modeled using mixed-effects linear regression and compared between those with and without ≥10% weight gain. Results: Among 1544 PWH who switched to only TAF, 2629 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/year before switching, age <40 years, and those discontinuing efavirenz. In those with ≥10% weight gain, 53.7% remained in the same body mass index (BMI) category, while a BMI change from normal/overweight at baseline to obesity at 24 months postswitch was seen in 13.9%, 11.7%, and 15.2% of those switching to only TAF, only INSTI, and 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

Frailty Is Associated With Mortality and Incident Comorbidity Among Middle-Aged Human Immunodeficiency Virus (HIV)-Positive and HIV-Negative Participants

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

Generally rare but occasionally severe weight gain after switching to an integrase inhibitor in virally suppressed AGEhIV cohort participants.

ObjectivesRecent studies have reported disproportionate weight gain associated with integrase strand transfer inhibitor (INSTI) initiation in antiretroviral therapy(ART)-naive people with HIV (PWH), particularly among black women. We investigated if HIV-positive AGEhIV participants with suppressed viremia switching to INSTI-containing ART experienced more weight gain compared to HIV-positive virally-suppressed non-switching and HIV-negative controls.MethodsIn the AGEhIV cohort, standardized weight measurements were performed biennially. Participants switching to INSTI-containing ART were 1:2:2 propensity score-matched with controls by age, gender, ethnicity and body mass index. Mean weight changes and proportions experiencing >5% or >10% weight gain were compared between study-groups using linear mixed-effects models and logistic regression, respectively.Results121 INSTI-switching participants and 242 participants from each of the control groups were selected. Across groups, median age was 53-55 years, 83-91% were male and 88-93% white. Mean weight change after switch among INSTI-switching participants was +0.14 kg/year (95%CI -0.25, +0.54) and similar among HIV-positive [+0.13 kg/year (95%CI +0.07, +0.33; P = .9)] and HIV-negative [+0.18 kg/year (95%CI 0.00, +0.37; P = .9)] controls. Weight gain >5% occurred in 28 (23.1%) INSTI-switching, 38 HIV-positive (15.7%, P = .085) and 32 HIV-negative controls (13.2%, P = .018). Weight gain >10% was rare.ConclusionsSwitching to INSTI-containing ART in our cohort of predominantly white men on long-term ART was not associated with greater mean weight gain, but >5% weight gain was more common than in controls. These results suggest that not all, but only certain, PWH may be particularly prone to gain a clinically significant amount of weight as a result of switching to INSTI

Human Immunodeficiency Virus (HIV)-Negative Men Who Have Sex with Men Have Higher CD8+T-Cell Counts and Lower CD4+/CD8+T-Cell Ratios Compared with HIV-Negative Heterosexual Men

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 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

Patterns of co-occurring comorbidities in people living with HIV

Background: The 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. Methods: A 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. Results: PCA 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). Conclusions: Comorbidities 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