Integrase strand transfer inhibitors (INSTIs) have been associated with weight gain among women living with HIV. We aimed to investigate the association between INSTIs and change in cardiometabolic ...risk indicators.
Retrospective cohort.
Data from 2006 to 2017 were analyzed from women living with HIV enrolled in the longitudinal Women's Interagency HIV Study who were virally controlled on antiretroviral therapy (ART) for ≥5 consecutive semiannual visits. Women who switched/added an INSTI to ART (INSTI group) were compared with women who remained on non-INSTI ART (non-INSTI group). Outcomes included changes in fasting lipids and glucose, hemoglobin A1c (HbA1c), blood pressure (BP), and incident diabetes, hypertension, and insulin resistance. Outcomes were measured 6-12 months before and 6-18 months after INSTI switch/add in the INSTI group with comparable visits in the non-INSTI group. Longitudinal linear regression models compared change over time in each outcome by the study group.
One thousand one hundred eighteen participants (234 INSTI, 884 non-INSTI) were followed for a median 2.0 (Q1 1.9, Q3 2.0) years. Participants were median age 49 years, 61% Black, and 73% overweight or obese (body mass index ≥25 kg/m). Compared with non-INSTI, the INSTI group experienced greater increases in HbA1c (+0.05 vs. -0.06 mg/dL, P = 0.0318), systolic BP (+3.84 vs. +0.84 mm Hg, P = 0.0191), and diastolic BP (+1.62 vs. -0.14 mm Hg, P = 0.0121), with greatest change in HbA1c among women on INSTIs with ≥5% weight gain.
INSTI use was associated with unfavorable changes in HbA1c and systolic and diastolic BP during short-term follow-up. Further research is needed to understand long-term cardiometabolic effects of INSTI use.
Aging in people with HIV is associated with increased risk of developing synergistic conditions such as neurocognitive impairment, polypharmacy, and falls. We assessed associations between ...polypharmacy (use of 5 or more non-ART medications), use of neurocognitive adverse effects (NCAE) medications, and odds of falls in women with HIV (WWH) and without HIV (HIV-).
Self-reported falls and medication use data were contributed semiannually by 1872 (1315 WWH and 557 HIV-) Women's Interagency HIV Study participants between 2014 and 2016. Polypharmacy and NCAE medication use were evaluated separately and jointly in multivariable models to assess their independent contributions to single and multiple falls risk.
The proportion of women who reported any fall was similar by HIV status (19%). WWH reported both greater polypharmacy (51% vs. 41%; P < 0.001) and NCAE medication use (44% vs. 37%; P = 0.01) than HIV- women. Polypharmacy conferred elevated odds of single fall adjusted odds ratio (aOR) 1.67, 95% CI: 1.36 to 2.06; P < 0.001 and multiple falls (aOR 2.31, 95% CI: 1.83 to 2.93; P < 0.001); the results for NCAE medications and falls were similar. Both polypharmacy and number of NCAE medications remained strongly and independently associated with falls in multivariable models adjusted for HIV serostatus, study site, sociodemographics, clinical characteristics, and substance use.
Polypharmacy and NCAE medication use were greater among WWH compared with HIV-, and both were independently and incrementally related to falls. Deprescribing and avoidance of medications with NCAEs may be an important consideration for reducing fall risk among WWH and sociodemographically similar women without HIV.
Persistent immune activation and microbial translocation associated with HIV infection likely place HIV-infected aging women at high risk of developing chronic age-related diseases. We investigated ...immune activation and microbial translocation in HIV-infected aging women in the post-menopausal ages.
Twenty-seven post-menopausal women with HIV infection receiving antiretroviral treatment with documented viral suppression and 15 HIV-negative age-matched controls were enrolled. Levels of immune activation markers (T cell immune phenotype, sCD25, sCD14, sCD163), microbial translocation (LPS) and biomarkers of cardiovascular disease and impaired cognitive function (sVCAM-1, sICAM-1 and CXCL10) were evaluated.
T cell activation and exhaustion, monocyte/macrophage activation, and microbial translocation were significantly higher in HIV-infected women when compared to uninfected controls. Microbial translocation correlated with T cell and monocyte/macrophage activation. Biomarkers of cardiovascular disease and impaired cognition were elevated in women with HIV infection and correlated with immune activation.
HIV-infected antiretroviral-treated aging women who achieved viral suppression are in a generalized status of immune activation and therefore are at an increased risk of age-associated end-organ diseases compared to uninfected age-matched controls.
Given the challenges and costs associated with implementing HIV-1 incidence assay testing, there is great interest in evaluating the use of commercial HIV diagnostic tests for determining recent HIV ...infection. A diagnostic test with the capability of providing reliable data for the determination of recent HIV infection without substantial modifications to the test protocol would have a significant impact on HIV surveillance. The Abbott ARCHITECT HIV Ag/Ab Combo Assay is an antigen/antibody immunoassay, which meets the criteria as the first screening test in the recommended HIV laboratory diagnostic algorithm for the United States.
In this study, we evaluated the performance characteristics of the ARCHITECT HIV Ag/Ab Combo signal-to-cutoff ratio (S/Co) for determining recent infection, including estimation of the mean duration of recent infection (MDRI) and false recent rate (FRR), and selection of recency cutoffs.
The MDRI estimates for the S/Co recency cutoff of 400 is within the 4 to 12 months range recommended for HIV incidence assays, and the FRR rate for this cutoff was 1.5%. Additionally, ARCHITECT Combo S/Co values were compared relative to diagnostic test results from two prior prospective HIV-1 diagnostic studies in order to validate the use of the S/Co for both diagnostic and recency determination.
Dual-use of the ARCHITECT Combo assay data for diagnostic and incidence purposes would reduce the need for separate HIV incidence testing and allow for monitoring of recent infection for incidence estimation and other public health applications.
To determine whether domain-specific neurocognitive (NC) impairments predict falls in HIV+ compared with HIV- women.
Cross-sectional data analysis from 825 HIV+ and 392 HIV- women in the Women's ...Interagency HIV Study with NC testing within 2 years before falls surveys.
NC impairment (T score <40) was assessed in 7 domains: executive function, psychomotor speed, attention, learning, memory, fluency, and fine motor function. For domains associated with any fall within 6 months in simple logistic regression (P < 0.05), hierarchical regression models evaluated associations between NC impairment and odds of falling, adjusting for: (1) study site and HIV, (2) demographics, (3) comorbid conditions, (4) substance use/central nervous system active medications, and HIV-specific factors.
Median age was higher in HIV+ than HIV- women (51 vs. 48 yrs); prevalence of falls was similar (19% HIV+, 16% HIV-). Overall, executive function OR (odds ratio) = 1.82, 95% CI (confidence interval): 1.21 to 2.74; P = 0.004, psychomotor speed (OR = 1.59, 95% CI: 1.05 to 2.42, P = 0.03), and fine motor (OR 1.70, 95% CI: 1.11 to 2.61, P = 0.02) impairments were associated with greater odds of falls in fully adjusted models. In fully adjusted models, associations of executive function, psychomotor speed, and fine motor were nonsignificant among HIV+ women; conversely, among HIV- women, associations with impaired executive and fine motor functions were strengthened and remained significant.
Cognitive impairment was associated with falls among middle-aged HIV- but not HIV+ women. Additional studies should elucidate mechanisms by which domain-specific NC impairment impacts fall risk among older HIV+ and HIV- women and how different factors modify relationships between cognition and falls.
Although fracture rates are higher in HIV+ than HIV- women, whether HIV infection increases risk of falls is unclear. We determined the longitudinal occurrence and risk factors for falls in the ...Women's Interagency HIV Study (WIHS), and explored associations with cognitive complaints.
Recent (prior 6 months) self-reported falls were collected in 1,816 (1,250 HIV+; 566 HIV-) women over 24 months. Generalized estimating equation models using stepwise selection determined odds of any fall (versus none).
HIV+ women were older than HIV- women (median 49 versus 47 years; P=0.0004), more likely to report neuropathy (20% versus 16%; P=0.023), and had greater central nervous system (CNS) medication use. At least one fall was reported in 41% HIV+ versus 42% HIV- women, including ≥2 falls in 25% HIV+ and 24% HIV- (overall P=0.30). Cognitive complaints were associated with falls among HIV+ (odds ratio OR 2.38; 95% CI 1.83, 3.09) and HIV- women (OR 3.43; 95% CI 2.37, 4.97); in adjusted models, cognitive complaints remained significant only in HIV- women (adjusted aOR 2.26; 95% CI 1.46, 3.48). Factors associated with any fall in adjusted analyses included: depressive symptoms and neuropathy (both HIV+ and HIV-); age, marijuana use, multiple CNS medications, and HCV infection (HIV+ only); and cognitive complaints, quality of life, hypertension and obesity (HIV- only).
Middle-aged HIV+ and HIV- women had similar fall rates. Among HIV+ women, factors affecting cognition such as age, depressive symptoms, marijuana use and multiple CNS medications were important predictors of falls, however, cognitive complaints were not.
Bacterial vaginosis (BV) is the most common female reproductive tract infection and is associated with an increased risk of acquiring and transmitting HIV by a mechanism that is not well understood. ...Gamma delta (GD) T cells are essential components of the adaptive and innate immune system, are present in the female reproductive tract, and play an important role in epithelial barrier protection. GD1 cells predominate in the mucosal tissue and are important in maintaining mucosal integrity. GD2 cells predominate in peripheral blood and play a role in humoral immunity and in the immune response to pathogens. HIV infection is associated with changes in GD T cells frequencies in the periphery and in the female reproductive tract. The objective of this study is to evaluate if changes in vaginal flora occurring with BV are associated with changes in endocervical GD T cell responses, which could account for increased susceptibility to HIV. Seventeen HIV-infected (HIV+) and 17 HIV-uninfected (HIV-) pre-menopausal women underwent collection of vaginal swabs and endocervical cytobrushes. Vaginal flora was assessed using the Nugent score. GD T cells were assessed in cytobrush samples by flow cytometry. Median Nugent score was 5.0 and 41% of women had abnormal vaginal flora. In HIV uninfected women there was a negative correlation between Nugent score and cervical GD1 T cells (b for interaction = - 0.176, p<0.01); cervical GD1 T cells were higher in women with normal vaginal flora than in those with abnormal flora (45.00% vs 9.95%, p = 0.005); and cervical GD2 T cells were higher in women with abnormal flora than in those with normal flora (1.70% vs 0.35%, p = 0.023). GD T cells in the genital tract are protective (GD1) and are targets for HIV entry (GD2). The decrease in cervical GD1 and increase in GD2 T cells among women with abnormal vaginal flora predisposes women with BV to HIV acquisition. We propose to use GD T cell as markers of female genital tract vulnerability to HIV.
Hepatitis D virus (HDV) requires co-infection with hepatitis B virus (HBV). Human immunodeficiency virus (HIV) shares transmission routes with these viruses. Among 4,932 US women infected with or ...at-risk for HIV during 1994-2015, HBV surface antigen (HBsAg) positivity was more common in women with HIV (2.8% vs. 1.2%;
= 0.001); HDV was more common among participants enrolled during 2013-2015 (
= 0.0004) and those with resolved rather than active hepatitis C (1.9% vs. 0.5%;
= 0.02). Among HBsAg-positive women (
= 117), HDV antibody prevalence was 22% and did not vary by HIV status; HDV infection was associated with the presence of advanced fibrosis/cirrhosis at enrollment (adjusted odds ratio, 5.70; 95% confidence interval, 1.46-22.29). Our results demonstrate the importance of HDV testing in HBV-infected US women.
To determine the frequency and risk factors for falls among middle-aged HIV+ and HIV- women in the Women's Interagency HIV Study (WIHS).
We quantified self-report of any and multiple (≥2) falls in ...the prior 6 months among 1,412 HIV+ and 650 HIV- women with mean age 48 years. Logistic regression was used to evaluate associations of demographics, behavioural factors, comorbid conditions and medications with odds of any fall (versus none) and multiple falls (versus ≤1 fall).
At least one fall was reported in 263 HIV+ (19%) versus 119 HIV- (18%) women, and ≥2 falls reported in 133 HIV+ (9%) versus 65 HIV- (10%) women. HIV infection was not associated with falls in multivariate analyses. Factors independently associated with any fall included age (adjusted odds ratio aOR 1.71, 95% CI 1.17, 2.49 age 50-59 versus <39 years; aOR 2.26, 95% CI 1.38, 3.71 age ≥60 versus <39), current marijuana use (aOR 2.19, 95% CI 1.53, 3.13) depressive symptoms (aOR 1.57, 95% CI 1.21, 2.05 for Center for Epidemiology Studies Depression score ≥16), subjective cognitive complaints (aOR 2.19, 95% CI 1.56, 3.08), neuropathy (aOR 1.59, 95% CI 1.19, 2.13), obesity (aOR 1.39, 95% CI 1.08, 1.80), number of central nervous system active agents (aOR 2.98, 95% CI 1.90, 4.68 for ≥3 agents versus 0) and WIHS site. Factors associated with ≥2 falls included age, marijuana use, number of central nervous system active agents, subjective cognitive complaints, depressive symptoms, neuropathy and study site.
Falls were associated with factors affecting cognition, but not HIV status in this large cohort of women. Longitudinal studies are needed to determine the incidence and consequences of falls by HIV status as women age.
Anal intercourse (AI) is not uncommon among U.S. women and, when condomless, confers a far greater likelihood of HIV transmission than condomless vaginal intercourse. We aim to identify determinants ...preceding AI, among women with, and women without HIV.
3708 women living with (73%), and without HIV (27%) participating in the Women's Interagency HIV Study provided sexual behavior and other data at 6-monthly visits over a median of 9 years (1994-2014). We used generalized estimating equation models to examine sociodemographic, structural and behavioral determinants reported in the visit preceding (1) AI, and (2) condomless AI.
AI was reported at least once over follow-up by 31% of women without, and 21% with HIV. AI was commonly condomless; reported at 76% and 51% of visits among women living without HIV, and with HIV, respectively. Women reporting AI were more likely to be younger (continuous variable, adjusted odds ratio (aOR) = 0.97, 95% confidence interval (CI):0.96-0.98), Hispanic (aOR = 1.88, CI:1.47-2.41) or White (aOR = 1.62, CI:1.15-2.30) compared to Black, and have at least high school education (aOR = 1.33, CI:1.08-1.65). AI was more likely following the reporting of either (aOR = 1.35, CI:1.10-1.62), or both (aOR = 1.77, CI:1.13-2.82) physical and sexual violence, excessive drinking (aOR = 1.27, CI:1.05-1.66) or any drug use (aOR = 1.34, CI:1.09-1.66), multiple male partners (aOR = 2.64, CI:2.23-3.11), exchange sex (aOR = 3.45, CI:2.53-4.71), one or more female sex partners (aOR = 1.32, CI:1.01-1.75), condomless vaginal intercourse (aOR = 1.80, CI:1.53-2.09), and high depressive symptoms (aOR = 1.23, CI:1.08-1.39).
AI disproportionally follows periods of violence victimization, substance use, multiple sex partners and depression. Better prevention messaging and biomedical interventions that reduce acquisition or transmission risk are needed, but when AI occurs in the context of violence against women, as our findings indicate, focusing on gender-based violence reduction and immediate treatment to reduce HIV transmission risk is important.
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