Cognitive changes during the menopausal transition: a longitudinal study in women with and without HIV

OBJECTIVE: To assess longitudinal changes in cognitive performance across menopause stages in a sample comprised primarily of low-income women of color, including women with HIV (WWH). METHODS: A total of 443 women (291 WWH; 69% African American; 18% Hispanic; median age = 42 y) from the Women's Interagency HIV Study completed tests of verbal learning and memory, attention/working memory, processing speed, verbal fluency, motor skills, and executive function first at an index premenopausal visit and thereafter once every 2 years for up to six visits (mean follow-up = 5.7 y). General linear-mixed effects regression models were run to estimate associations between menopause stages and cognition, in the overall sample and in WWH. We examined both continuous scores and categorical scores of cognitive impairment (yes/no >1 standard deviation below the mean). RESULTS: Adjusting for age and relevant covariates, the overall sample and WWH showed longitudinal declines in continuous measures of learning, memory, and attention/working memory domains from the premenopause to the early perimenopause and from the premenopause to the postmenopause, Ps < 0.05 to < 0.001. Effects on those same domains were also evident in categorical scores of cognitive impairment, with the increased odds of impairment ranging from 41% to 215%, Ps < 0.05 to < 0.001. The increase in predicted probability of impairment by menopausal stage (% affected) ranged from 4% to 13%. CONCLUSIONS: Menopause stage was a key determinant of cognition in a sample of low-income women of color, including WWH. Many of these changes reached a clinically significant level of cognitive impairment

Associations between HIV, antiretroviral therapy and preterm birth in the US Women’s Interagency HIV Study, 1995–2018: a prospective cohort

Objective: To evaluate the associations of HIV infection with preterm birth (PTB), and of HIV antiretroviral therapy (ART) with PTB. Methods: We analysed singleton live-born pregnancies among women from 1995 to 2019 in the Women's Interagency HIV Study, a prospective cohort of US women with, or at risk for, HIV. The primary exposures were HIV status and ART use before delivery [none, monotherapy or dual therapy, or highly active antiretroviral therapy (HAART)]. The primary outcome was PTB < 34 weeks, and, secondarily, < 28 and < 37 weeks. We analysed self-reported birth data, and separately modelled the associations between HIV and PTB, and between ART and PTB, among women with HIV. We used modified Poisson regression, and adjusted for age, race, parity, tobacco use and delivery year, and, when modelling the impact of ART, duration from HIV diagnosis to delivery, nadir CD4 count, and pre-pregnancy viral load and CD4 count. Results: We analysed 488 singleton deliveries (56% exposed to HIV) to 383 women. The risk of PTB < 34 weeks was similar among women with and without HIV, but the risk of PTB < 37 weeks was higher [32% vs. 23%; adjusted risk ratio (aRR) = 1.43; 95% confidence interval (CI): 1.07–1.91] among women with HIV. The risk of PTB < 34 weeks was lower among women with HIV receiving HAART than among those receiving no ART (7% vs. 26%; aRR:0.19; 95% CI: 0.08–0.44). The associations between HAART and PTB < 28 and < 37 weeks were similar. Conclusions: Antiretroviral therapy exposure was associated with a decreased risk of PTB among a US cohort of women with HIV. Given the growing concerns about ART and adverse pregnancy outcomes, this finding that ART may be protective for PTB is reassuring

Association between BMI and periodontitis in women living with or at risk for HIV

Aims: Currently, there is no data available assessing the association between body mass index (BMI) and periodontitis among women living with HIV (WLWH). This study aims to investigate this association among WLWH and women at risk for HIV (WRH) in the United States. Methods and results: Data from 351 WLWH and 52 WRH participants from the Women's Interagency HIV Study having pocket depths and clinical periodontal attachment loss assessments in 2003–2004 were included. Multinomial logistic regression analyses in the full sample assessed the relationship between BMI (underweight/normal, overweight, or obese) and periodontitis by severity (mild, moderate, severe), adjusting for study sites, age, education, annual household income, smoking, alcohol consumption, and diabetes. Overall, 75.2% women (76.0% WLWH; 69.0% WRH) had periodontitis. Moreover, 75.0% obese and 75.3% overweight women were affected by periodontitis. In the full sample, adjusted odds ratio (aOR) of having mild, moderate, and severe periodontitis in obese women were: 1.14 (95% confidence interval [CI]: 0.51–2.52), 1.02 (95% CI: 0.46–2.29), and 0.24 (95% CI: 0.06–1.07), respectively, and in overweight women: 0.70 (95% CI: 0.31–1.58), 0.85 (95% CI: 0.38–1.90), and 0.31 (95% CI: 0.08–1.15), respectively. Conclusions: Even with high prevalence of periodontitis among women with or without HIV infection in this cohort, this study does not provide evidence of an association between BMI and periodontitis

Examining adherence barriers among women with HIV to tailor outreach for long-acting injectable antiretroviral therapy

Background: Long-acting (LA) injectable antiretroviral therapy (ART) has been found non-inferior to daily oral ART in Phase 3 trials. LA ART may address key barriers to oral ART adherence and be preferable to daily pills for some people living with HIV. To date, women have been less represented than men in LA ART research. Using longitudinal data from the Women's Interagency HIV Study (WIHS) cohort of women living with HIV in the United States, we examined barriers and facilitators of daily oral ART adherence that may be related to or addressed by LA ART. Methods: We conducted a secondary analysis of WIHS cohort data from 1998 to 2017 among participants seen for at least 4 visits since 1998 who reported using ART at least once (n = 2601). Two dichotomous outcomes, patient-reported daily oral ART adherence and viral suppression were fit using generalized linear models, examining the role of socio-demographic and structural factors. Results: At study enrollment, the median age was 40.5 years, 63% of participants were African American and 22% were Latina. The majority (82%) reported taking ART more than 75% of the time and 53% were virally suppressed. In multivariate analysis, several sub-groups of women had lower odds of reported adherence and viral suppression: 1) younger women (adherence aOR: 0.71; viral suppression aOR: 0.63); 2) women who inject drugs (adherence aOR: 0.38; viral suppression aOR: 0.50) and those with moderate (adherence aOR: 0.59; viral suppression aOR: 0.74) and heavy alcohol consumption (adherence aOR: 0.51; viral suppression aOR: 0.69); 3) those with depressive symptoms (adherence aOR: 0.61; viral suppression aOR: 0.76); and 4) those with a history of going on and off ART (adherence aOR: 0.62, viral suppression aOR: 0.38) or changing regimens (adherence aOR: 0.83, viral suppression aOR: 0.56). Conclusions: Current injectable contraceptive users (vs. non-users) had greater odds of oral ART adherence (aOR: 1.87) and viral suppression (aOR: 1.28). Findings identify profiles of women who may benefit from and be interested in LA ART. Further research is warranted focused on the uptake and utility of LA ART for such key subpopulations of women at high need for innovative approaches to achieve sustained viral suppression

Hormone therapy and fractures in postmenopausal women

Background:Fracture rates have been reported to be higher among older women living with HIV (WLWH) than HIV- women. Hormone therapy with estrogen can reduce vasomotor symptoms (VMS) associated with menopause and prevent fractures. As data are limited on the benefits of hormone therapy use in WLWH, we examined associations of hormone therapy, use and fractures.Methods:A prospective study of 1765 (1350 WLWH and 415 HIV-) postmenopausal Women's Interagency HIV Study (WIHS) participants was performed, including self-reported hormone therapy, use and fracture data from 2003 to 2017. Proportional hazard models determined predictors of new fractures at any site or at typical fragility fracture sites (hip, spine, wrist).Results:At the first postmenopausal visit, the median (IQR) age of WLWH was slightly younger than HIV- women [49.8 (46.4-53) vs. 50.7 (47.5-54), P = 0.0002] and a smaller proportion of WLWH reported presence of VMS (17% vs. 26%, P < 0.0001). A greater proportion of WLWH than HIV- women reported hormone therapy use (8% vs. 4%, P = 0.007) at the first postmenopausal visit. In multivariate analyses, white race and smoking were significant predictors of incident fracture at any site but hormone therapy (P = 0.69) and HIV status (P = 0.53) were not.Conclusion:Our study did not find evidence of benefit or harm with regards to fracture outcomes in postmenopausal WLWH receiving hormone therapy. Further research is needed to determine whether hormone therapy has benefits beyond treatment of VMS, such as prevention of adverse aging-associated outcomes

Poverty, Deprivation, and Mortality Risk among Women with HIV in the United States

Background: Prior studies suggest neighborhood poverty and deprivation are associated with adverse health outcomes including death, but evidence is limited among persons with HIV, particularly women. We estimated changes in mortality risk from improvement in three measures of area-level socioeconomic context among participants of the Women's Interagency HIV Study. Methods: Starting in October 2013, we linked geocoded residential census block groups to the 2015 Area Deprivation Index (ADI) and two 2012-2016 American Community Survey poverty variables, categorized into national tertiles. We used parametric g-computation to estimate, through March 2018, impacts on mortality of improving each income or poverty measure by one and two tertiles maximum versus no improvement. Results: Of 1596 women with HIV (median age 49), 91 (5.7%) were lost to follow-up and 83 (5.2%) died. Most women (62%) lived in a block group in the tertile with the highest proportions of individuals with income:poverty <1; 13% lived in areas in the tertile with the lowest proportions. Mortality risk differences comparing a one-tertile improvement (for those in the two highest poverty tertiles) in income:poverty <1 versus no improvement increased over time; the risk difference was -2.2% (95% confidence interval [CI] = -3.7, -0.64) at 4 years. Estimates from family income below poverty level (-1.0%; 95% CI = -2.7, 0.62) and ADI (-1.5%; 95% CI = -2.8, -0.21) exposures were similar. Conclusions: Consistent results from three distinct measures of area-level socioeconomic environment support the hypothesis that interventions to ameliorate neighborhood poverty or deprivation reduce mortality risk for US women with HIV. See video abstract at, http://links.lww.com/EDE/B863

Decreases in markers of monocyte/macrophage activation after hepatitis C eradication in HIV/hepatitis C virus coinfected women

Objective:Eradication of hepatitis C virus (HCV) in HIV disease decreases liver and non-liver-related morbidity and mortality. Elevated markers of monocyte/macrophage activation (soluble CD163 and sCD14) are associated with excess non-AIDS morbidity and mortality in HIV. We examined the effect of HCV eradication on these markers in relation to change in hepatic fibrosis.Design:A nested substudy within a longitudinal observational cohortMethods:We studied 126 HIV/HCV-coinfected women successfully treated for HCV, with undetectable HCV RNA at least 12 weeks after therapy completion. sCD163 and sCD14 were measured in serum collected before and after HCV eradication. Results were correlated with changes in markers of hepatic fibrosis.Results:Mean age of participants was 56.3 years, mean CD4+cell count was 615, and 72% had suppressed HIV RNA. After treatment, sCD163 and sCD14 levels significantly decreased from pre-treatment levels in unadjusted analyses. After adjusting for age, race, hepatic fibrosis status, baseline HCV RNA, CD4 count and HIV RNA status, cigarette smoking, and alcohol use, the decreases in sCD163 and sCD14 remained significant. Decrease in pre-treatment to post-treatment sCD163 were significantly positively correlated with changes in FIB-4 (r = 0.250, P = 0.005) and APRI (r = 0.262, P = 0.003); similarly decrease in sCD14 was significantly positively correlated with changes in FIB-4 (r = 0.333, P = 0.0001) and APRI (r = 0.457, P &lt; 0.0001).Conclusion:HCV eradication is associated with significant reductions in monocyte/macrophage activation markers that correlate with reductions in markers of hepatic fibrosis. These findings support broad access to and early initiation of HCV treatment in order to decrease immune activation and improve health in HIV-infected persons

Class-Based Antiretroviral Exposure and Cognition Among Women Living with HIV

Neurologic complications of the human immunodeficiency virus (HIV) are common in treated individuals, and toxicity of certain antiretroviral therapies (ART) may contribute to cognitive impairment. We investigated exposures to specific ART and cognition among women living with HIV (WLWH). Virologically suppressed (viral load <200 copies/mL during at least two semi-annual visits) WLWH and age/race matched HIV-seronegative controls enrolled in the Women's Interagency HIV Study who completed at least two biennial cognitive assessments were included. Analysis of WLWH was restricted to those with exposure to the drug class of interest and a nucleoside reverse transcriptase inhibitor (NRTI) backbone. Generalized estimating equations were used to evaluate repeated measures of cognition over time in association with ART class exposure. Among 1,242 eligible WLWH, 20% (n = 247) had isolated drug exposure to non-nucleoside reverse transcriptase inhibitors (NNRTI), 18% (n = 219) to protease inhibitors (PIs), and 6% (n = 79) to integrase inhibitors with a NRTI backbone. Cognitive assessments were performed at a median of 3 biennial visits {IQR 2-4 visits}. At the index assessment, 21% of WLWH demonstrated global cognitive impairment versus 29% at their last cognitive assessment. In multivariable analyses adjusted for hypertension, depression, diabetes mellitus, history of AIDS-defining illness, alcohol use, number of medications, and time on ART, WLWH exposed to NNRTIs demonstrated verbal learning improvements (mean T-score change 1.3, p = .020) compared to other treated women. Compared to HIV-seronegative women, WLWH exposed to PIs had worse verbal learning (mean T-score difference -2.62, p = .002) and verbal memory performance (mean T-score difference -1.74, p = .032) at baseline. Compared to HIV-seronegative women, WLWH exposed to PIs had improvements in verbal learning (mean T-score slope difference 0.36, p = .025) and verbal memory (mean T-score slope difference 0.32, p = .042). The index T-score and slope of change in the T-score were similar among other treated groups and the HIV-seronegative group. We noted emerging trends in cognition in WLWH exposed to specific drug classes. Ongoing study of this relatively young group is important to characterize long-term cognitive outcomes and effect of antiretrovirals as treatment guidelines evolve

Substance use and its predictors among undergraduate medical students of Addis Ababa University in Ethiopia

<p>Abstract</p> <p>Background</p> <p>Substance use remains high among Ethiopian youth and young adolescents particularly in high schools and colleges. The use of alcohol, <it>khat </it>and tobacco by college and university students can be harmful; leading to decreased academic performance, increased risk of contracting HIV and other sexually transmitted diseases. However, the magnitude of substance use and the factors associated with it has not been investigated among medical students in the country. This study was conducted to determine the prevalence of substance use and identify factors that influenced the behavior among undergraduate medical students of Addis Ababa University in Ethiopia.</p> <p>Methods</p> <p>A cross-sectional study using a pre-tested structured self-administered quantitative questionnaire was conducted in June 2009 among 622 medical students (Year I to Internship program) at the School of Medicine. The data were entered into Epi Info version 6.04d and analyzed using SPSS version 15 software program. Descriptive statistics were used for data summarization and presentation. Differences in proportions were compared for significance using Chi Square test, with significance level set at p < 0.05. Multivariate logistic regression analyses were used to assess the magnitude of associations between substance use and socio-demographic and behavioral correlates.</p> <p>Results</p> <p>In the last 12 months, alcohol was consumed by 22% (25% males vs. 14% females, p = 0.002) and <it>khat </it>use was reported by 7% (9% males vs. 1.5% females, p < 0.001) of the students. About 9% of the respondents (10.6% males vs. 4.6% females, p = 0.014) reported ever use of cigarette smoking, and 1.8% were found to be current smokers. Using multiple logistic regression models, being male was strongly associated with alcohol use in the last 12 months (adjusted OR = 2.14, 95% CI = 1.22-3.76). Students whose friends currently consume alcohol were more likely to consume alcohol (adjusted OR = 2.47, 95% CI = 1.50-4.08) and whose friends' use tobacco more likely to smoke (adjusted OR = 3.89, 95% CI = 1.83-8.30). <it>Khat </it>use within the past 12 months was strongly and positively associated with alcohol consumption (adjusted OR = 15.11, 95% CI = 4.24-53.91). Similarly, ever use of cigarette was also significantly associated with alcohol consumption (adjusted OR = 8.65, 95% CI = 3.48-21.50).</p> <p>Conclusions</p> <p>Concordant use of alcohol, <it>khat </it>and tobacco is observed and exposure to friends' use of substances is often implicated. Alcohol consumption or <it>khat </it>use has been significantly associated with tobacco use. While the findings of this study suggest that substance use among the medical students was not alarming, but its trend increased among students from Year I to Internship program. The university must be vigilant in monitoring and educating the students about the consequences of substance use.</p