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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.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).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.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.

BACKGROUND: 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−). METHODS: Self-reported falls and medication use data were contributed semiannually by 1872 (1315 WWH, 557 HIV−) Women’s Interagency HIV Study (WIHS) 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. RESULTS: The proportion of women who reported any fall was similar by HIV status (19%). WWH reported both greater polypharmacy (51 % vs 41%; p

BACKGROUND Frailty may occur at younger ages among HIV+ populations. We evaluated associations of the frailty status with self-reported single and recurrent falls in the Women's Interagency HIV Study (WIHS). METHODS The frailty status was defined using the Fried Frailty Phenotype (FFP) among 897 HIV+ and 392 HIV- women; median age 53 years. Women were classified as robust (FFP 0), prefrail (FFP 1-2), and frail (FFP 3-5). Stepwise logistic regression models adjusting for the HIV status and study site were fit to evaluate associations of the FFP with self-reported single (1 vs. 0) and recurrent falls (≥2 vs. 0) over the prior 12 months. RESULTS HIV+ women were less likely to be frail (9% vs. 14% vs. P = 0.009), but frequency of falls did not differ by the HIV status. In multivariate analyses, recurrent falls were more common among prefrail [adjusted odds ratio (AOR) 2.23, 95% confidence interval (CI): 1.40 to 3.57, P = 0.0008] and frail (AOR 3.61, 95% CI: 1.90 to 6.89, P < 0.0001) than robust women. Among HIV+ women, single (AOR 2.88, 95% CI: 1.16 to 7.20, P = 0.023) and recurrent falls (AOR 3.50, 95% CI: 1.24 to 9.88, P = 0.018) were more common among those who were frail; recurrent, but not single falls, were more common among prefrail than robust HIV+ women (AOR 2.00, 95% CI: 1.03 to 3.91, P = 0.042). CONCLUSIONS HIV+ women were less likely to be frail. Compared with robust women, prefrail and frail women with and without HIV were more likely to experience single or recurrent falls within a 12-month period. Additional studies are needed to develop interventions that decrease development of frailty and reduce risk of recurrent falls among HIV+ women.

The number of people with HIV (PWH) experiencing age-associated comorbidities including those treated with medications and cognitive impairment is increasing. We examined associations between polypharmacy and cognition in older women with HIV (WWH) given their vulnerability to this comorbidity. Cross-sectional analysis capitalizing on Women's Interagency HIV Study data collected between 2014 and 2017. WWH meeting the following criteria were analyzed: age ≥50 years; availability of self-reported non-antiretroviral therapy (ART) medications data; and neuropsychological data. The number of non-ART medications used regularly in the prior 6 months was summed. Polypharmacy was categorized as none/low (0–4), moderate (5–9), or severe (≥10). Multivariable linear regression analyses examined polypharmacy-cognition (T-score) associations in the total sample and among virally suppressed (VS; < 20 copies/mL)-WWH after covariate adjustment for enrollment site, income, depressive symptoms, substance use (smoking, heavy alcohol, marijuana, crack, cocaine, and/or heroin), the Veterans Aging Cohort Study index (indicators of HIV disease and organ system function, hepatitis C virus serostatus), ART use, nadir CD4 count, and specific ART drugs (efavirenz, integrase inhibitors). We included 637 women (median age = 55 years; 72% Black). Ninety-four percent reported ART use in the past 6 months and 75% had HIV RNA

Purpose To evaluate the association between Medicaid expansion and diabetic dilated eye examinations. Design A retrospective difference in differences (DiD) analysis using individual-level survey response data from January 1, 2009, to December 31, 2017. Participants A total of 52 392 survey responses from 50 states and the District of Columbia between 2009 and 2017. Responders were adults aged 18 to 64 years reporting a previous diagnosis of diabetes and a household income below 138% of the US federal poverty line (FPL). Methods The Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System data were used to identify survey responders who were asked about the presence of dilated eye examinations from years before and after Medicaid expansion implementation. Main Outcome Measures The DiD in proportion of dilated eye examinations among diabetic persons aged 18 to 64 years with household incomes below 138% of the FPL between states that did and did not implement Medicaid expansion. Results Implementation of Medicaid expansion policies was associated with a 1.3% (95% confidence interval [CI], −3.8 to 6.4; P = 0.61), 6.3% (95% CI, 1.3–11.3; P = 0.016), 4.1% (95% CI, −0.8 to 9.0; P = 0.11), and 2.3% (95% CI, −1.6 to 6.2; P = 0.23) increase in the proportion of diabetic persons aged 18 to 64 years with incomes below 138% of the FPL receiving a dilated eye examination within the past year due to Medicaid expansion 1, 2, 3, and 4 cumulative years after expansion, respectively. Conclusions Medicaid expansion policies were significantly associated with an increase in dilated eye examination rates within the first 2 years after implementation. However, this increase did not persist beyond this period, with nonsignificant increases 3 and 4 cumulative years after implementation. Healthcare policymakers should be aware that additional measures beyond expanding insurance coverage may be necessary to increase and sustain the rate of dilated eye examinations among diabetic populations.

BackgroundReproductive tract infections (RTIs) are a major cause of morbidity and mortality, yet RTI testing remains limited in resource-constrained settings. We assessed performance of an existing RTI risk assessment screening tool among women living with HIV (WLHIV) considering intrauterine contraceptive (IUC) use.MethodsWe conducted a cross-sectional analysis among WLHIV screened for participation in an IUC trial in Cape Town, South Africa (NCT01721798). RTI testing included Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and bacterial vaginosis. Tool scoring was based on five separately scored criteria: (1) age under 25 years, (2) cohabitation with a partner, (3) secondary education, (4) self-reported intermenstrual bleeding and (5) number of current sexual partners and condom use frequency (score 0–5). We assessed tool performance in detecting RTI at 0 vs 1–5, 0–1 vs 2–5 and 0–2 vs 3–5 score thresholds.ResultsOf 303 women, 52% (n=157) reported antiretroviral therapy use and median age was 31 years. The prevalence of any RTI was 38% (gonorrhoea=7%, chlamydia=11%, trichomoniasis=12% and bacterial vaginosis=18%) and 8% of women had multiple RTIs. Overall, 4%, 27% and 69% of women had screening tool scores of 0, 1 or 2+, respectively. At a threshold of at least one scored criterion, the tool demonstrated high sensitivities (95%–97%) but low specificities (3%–4%) for detecting any RTI. Increasing the score threshold and/or inclusion of abnormal vaginal discharge marginally improved specificity.ConclusionThe prevalence of RTIs observed in this population was high, and the screening tool had no discriminatory power to detect prevalent RTIs.

OBJECTIVE To determine whether domain-specific neurocognitive (NC) impairments predict falls in HIV+ compared with HIV- women. DESIGN 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. METHODS NC impairment (T score

This study was conducted among predominately African American/Black women, aged 18-29, in Northeast cities with high HIV prevalence. Demographic, behavioral, and partner characteristics associated with condomless vaginal and anal sex acts with high-risk partners (CVS-HRP and CAS-HRP) and with HIV testing were explored. The high-risk sample was largely recruited online. Of 4972 women screened, 2254 (45.3%) were high-risk for HIV acquisition; 2214 were included. Bivariate and stepwise multivariate logistic regression models were fit. After adjusting for other factors, sex risk behavior did not differ by race and ethnicity. CAS-HRP was associated with believing condoms don't reduce HIV risk and with several high-risk behaviors, including; alcohol use, multiple partners, and sex with men who had sex with men, but, not with HIV testing. Half the sample had condomless sex with partners who never HIV tested and were themselves three times as likely to have never tested. These results point to the ongoing need for effective prevention strategies among at-risk heterosexual women.

Background The only way to systematically screen for self-neglect among older adults is through in-home observations, which are often difficult and unfeasible for healthcare providers. To fill this gap, we need a robust and efficient prognostication tool to better treat and prevent self-neglect among older adults. Objectives To develop a predictive index that can be used to assess risk prognostication of the onset of self-neglect among community-dwelling older populations. Design Two waves of longitudinal data from the Chicago Health and Aging Project (CHAP), collected during 2008 to 2012 with approximately 3-year follow-up intervals. Setting Non-Hispanic black or non-Hispanic white community-dwelling older adults in three adjacent neighborhoods in Chicago, IL. Participants A total of 2885 individuals who were participants of the CHAP study. Measurements The main outcomes are incident self-neglect cases. A total of 86 potential predictors were considered in the domains of sociodemographic and socioeconomic, general well-being, health behavior, medical health, medicine/healthcare, cognitive function, physical well-being, social well-being, and psychological well-being. Results The 3-year self-neglect incidence rate is 241 (8.4%). A 10-item predictive model (with a c-statistic of 0.76) was developed using stepwise selection in multivariable logistical regression models. After corrections of overfitting by validating in 100 bootstrapping samples, the predictive accuracy of the model dropped to 0.71, suggesting at least moderate overfitting. A point-based risk index was developed based on parameter estimates of each predictive factor in the final logistic model. The index has an area under the receiver operating characteristic curve of 0.76. Conclusion The study developed an efficient index with good predictive ability of self-neglect. Further external validation and impact studies are necessary before practitioners can apply this index to determine risk of self-neglect among other community aging populations. J Am Geriatr Soc 68:809-816, 2020.

Bone loss and cognitive impairment are common in women living with HIV (WLWH) and are exacerbated by menopause. Bone-derived undercarboxylated osteocalcin (ucOCN) and sclerostin appear to influence cognition. The current study investigated whether the circulating levels of these 2 proteins are associated with cognition in midlife WLWH and demographically similar HIV seronegative women.Plasma samples from women enrolled in a musculoskeletal substudy within the Women's Interagency HIV Study were used to measure ucOCN and sclerostin. A neuropsychological (NP) test battery assessing executive function, processing speed, attention/working memory, learning, memory, verbal fluency, and motor function was administered within 6 months of musculoskeletal enrollment and every 2 years after (1-4 follow-up visits per participant). A series of generalized estimating equations were conducted to examine the association between biomarkers and NP performance at the initial assessment and over time in the total sample and in WLWH only. Primary predictors included biomarkers, time, and biomarker by time interactions. If the interaction terms were not significant, models were re-run without interactions.Neither biomarker predicted changes in NP performance over time in the total sample or in WLWH. ucOCN was positively associated with executive function in the total sample and in WLWH and with motor skills in WLWH. ucOCN was negatively associated with attention/working memory in the total sample. There were no significant associations between sclerostin and NP performance.The current study suggests an association between bone-derived ucOCN and cognition in women with and without HIV infection.

Background We previously reported lower bone mineral density (BMD) among premenopausal women with HIV (WWH) compared to women without HIV (HIV−). Rate of bone loss may be even greater for WWH during the menopausal transition. Methods Pre-, peri- and postmenopausal women in the Women\'s Interagency HIV Study (WIHS) underwent whole body DXA and central quantitative computed tomography to measure areal BMD (aBMD) and volumetric BMD (vBMD), respectively. Multivariable regression models with covariates associated with low aBMD (T score < −1.0) in univariate analyses (P≤.05) and known risk factors for low BMD assessed contributions of HIV and menopausal stage to the prediction of aBMD. Results Compared to HIV− women, in unadjusted analyses, WWH had 5–9% lower aBMD at the lumbar spine (P=.001), femoral neck (P=.04), total hip (P=.003) and the ultradistal radius (P=.004), and higher osteoporosis prevalence (T score Conclusions HIV infection and menopausal stage were independent predictors of lower BMD, and had an additive effect on lumbar spine and total hip BMD. Additional research is needed to better understand underlying mechanisms by which HIV impacts BMD as women age and transition through menopause, and develop strategies to mitigate osteoporosis and fracture risk in this growing population.

Introduction The Central Africa International epidemiology Database to Evaluate AIDS (CA‐IeDEA) is an open observational cohort study investigating impact, progression and long‐term outcomes of HIV/AIDS among people living with HIV (PLWH) in Burundi, Cameroon, Democratic Republic of Congo (DRC), Republic of Congo (ROC) and Rwanda. We describe trends in demographic, clinical and immunological characteristics as well as antiretroviral therapy (ART) use of patients aged > 15 years entering into HIV care in the participating CA‐IeDEA site. Methods Information on sociodemographic characteristics, height, weight, body mass index (BMI), CD4 cell count, WHO staging and ART status at entry into care from 2004 through 2018 were extracted from clinic records of patients aged > 15 years enrolling in HIV care at participating clinics in Burundi, Cameroon, DRC, ROC and Rwanda. We assessed trends in patient characteristics at enrolment in HIV care including ART initiation within the first 30 days after enrolment in care and calculated proportions, means and medians (interquartile ranges) for the main variables of interest. Results Among 69,176 patients in the CA‐IeDEA cohort, 39% were from Rwanda, 24% from ROC, 18% from Cameroon, 14% from Burundi and 5% from DRC. More women (66%) than men enrolled in care and subsequently initiated ART. Women were also younger than men (32 vs. 38 years, P

Diabetes mellitus (DM) is associated with expansion of proinflammatory lymphocyte subsets. We investigated the relationship of total white blood cell (WBC) count and lymphocyte subsets with incident DM in the Women's Interagency HIV Study (WIHS). Higher CD4 and CD8 T cell counts, lymphocyte count, and total WBC count were associated with incident DM among both women with and without HIV, although the association of CD8 was not statistically significant among women without HIV.

Background We describe the timing of human immunodeficiency virus (HIV) diagnosis and antiretroviral treatment (ART) initiation after implementation of universal testing and treatment policies in New York City (NYC). Methods Using NYC population-based HIV registry data for persons with HIV diagnosed from 2012 through 2015 and followed up through June 2017, we examined trends in the proportion with diagnosis soon after HIV infection (ie, with CD4 cell count ≥500/μL or with acute HIV infection) and used Kaplan-Meier plots and proportional hazards regression to examine the timing of ART initiation after diagnosis. Results Among 9987 NYC residents with HIV diagnosed from 2012 to 2015, diagnosis was early in 35%, and 87% started ART by June 2017. The annual proportion of persons with early diagnosis did not increase appreciably (35% in 2012 vs 37% in 2015; P = .08). By 6 months after diagnosis, 62%, 67%, 72% and 77% of persons with HIV diagnosed in 2012, 2013, 2014, or 2015, respectively, had started ART, with median (interquartile range) times to ART initiation of 3.34 (1.34–12.75), 2.62 (1.28–10.13), 2.16 (1.15–7.11), and 2.03 (1.11–5.61) months, respectively. Conclusions Although recommendations for ART initiation on diagnosis are increasingly being implemented, the findings of the current study suggest that immediate treatment initiation is not universal. Continued efforts are needed to expand and better target HIV testing to promote earlier diagnosis.

Background Frailty and falls occur commonly and prematurely in HIV-infected populations. Whether frailty in middle-age predicts future falls among HIV-infected women is unknown. Methods We evaluated associations of frailty with single and recurrent falls 10 years later among 729 HIV-infected and 326 uninfected women in the Women's Interagency HIV Study (WIHS) with frailty measured in 2005 and self-reported falls in 2014–2016. Frailty was defined as ≥3 of 5 Fried Frailty Index components: slow gait, reduced grip strength, exhaustion, unintentional weight loss and low physical activity. Stepwise logistic regression models determined odds of single (versus 0) or recurrent falls (≥2 versus 0) during the 2-year period; separate models evaluated frailty components. Results HIV-infected women were older (median 42 versus 39 years; PConclusions Early frailty measurement among middle-aged women with or at-risk for HIV may be a useful tool to assess future fall risk.

Introduction Lifestyle improvements are key modifiable risk factors for Type 2 diabetes mellitus (DM) however specific influences of biologically active dietary metabolites remain unclear. Our objective was to compare non-targeted plasma metabolomic profiles of women with versus without confirmed incident DM. We focused on three lipid classes (fatty acyls, prenol lipids, polyketides). Materials and methods Fifty DM cases and 100 individually matched control participants (80% with human immunodeficiency virus [HIV]) were enrolled in a case-control study nested within the Women’s Interagency HIV Study. Stored blood samples (1–2 years prior to DM diagnosis among cases; at the corresponding timepoint among matched controls) were assayed in triplicate for metabolomics. Time-of-flight liquid chromatography mass spectrometry with dual electrospray ionization modes was utilized. We considered 743 metabolomic features in a two-stage feature selection approach with conditional logistic regression models that accounted for matching strata. Results Seven features differed by DM case status (all false discovery rate-adjusted q Conclusion Flavonoids were associated with lower odds of incident DM while sorbic acid was associated with greater odds of incident DM.

Background Time of day has been associated with variations in certain clinical practices such as cancer screening rates. In this study, we assessed how more general process measures of physician activity, particularly rates of diagnostic test ordering and diagnostic assessments, might be affected by time of day. Methods We conducted a retrospective chart review of 3,342 appointments by 20 attending physicians at five outpatient clinics, matching appointments by physician and comparing the average diagnostic tests ordered and average diagnoses assessed per appointment in the first hour of the day versus the last hour of the day. Statistical analyses used sign tests, two-sample t-tests, Wilcoxon tests, Kruskal Wallis tests, and multivariate linear regression. Results Examining physicians individually, four and six physicians, respectively, had statistically significant first- versus last-hour differences in the number of diagnostic tests ordered and number of diagnoses assessed per patient visit (p ≤ 0.04). As a group, 16 of 20 physicians ordered more tests on average in the first versus last hour (p = 0.012 for equal chance to order more in each time period). Substantial intra-clinic heterogeneity was found in both outcomes for four of five clinics (p < 0.01). Conclusions There is some statistical evidence on an individual and group level to support the presence of time-of-day effects on the number of diagnostic tests ordered per patient visit. These findings suggest that time of day may be a factor influencing fundamental physician behavior and processes. Notably, many physicians exhibited significant variation in the primary outcomes compared to same-specialty peers. Additional work is necessary to clarify temporal and inter-physician variation in the outcomes of interest.

Background Antiretroviral therapy (ART) success has led people to live longer with HIV/AIDS (PLWH) and thus be exposed to increasing risk of cardiovascular diseases (CVD). Hypertension (HTN), the biggest contributor to CVD burden, is a growing concern among PLWH. The current report describes the prevalence and predictors of HTN among PLWH in care in Cameroon. Methods This cross-sectional study included all PLWH aged 20 years and above who received care between 2016 and 2019 at one of the three Central Africa International Epidemiology Databases to Evaluate AIDS (CA-IeDEA) sites in Cameroon (Bamenda, Limbe, and Yaoundé). HTN was defined as blood pressure (BP) ≥140/90 mm Hg or self-reported use of antihypertensive medication. Logistic regressions models examined the relationship between HTN and clinical characteristics, and HIV-related factors. Results Among 9,839 eligible PLWH, 66.2% were women and 25.0% had prevalent HTN [age-standardized prevalence 23.9% (95% CI: 22.2–25.6)], among whom 28 (1.1%) were on BP lowering treatment, and 6 of those (21.4%) were at target BP levels. Median age (47.4 vs. 40.5 years), self-reported duration of HIV infection (5.1 vs 2.8 years years), duration of ART exposure (4.7 vs 2.3 years), and CD4 count (408 vs 359 cell/mm3) were higher in hypertensives than non-hypertensives (all p Conclusion About a quarter of these Cameroonian PLWH had HTN, driven among others by age and adiposity. Appropriate integration of HIV and NCDs services is needed to improve early detection, treatment and control of common comorbid NCD risk factors like hypertension and safeguard cardiovascular health in PLWH.

Background Bone mineral density (BMD) loss and fat accumulation are common in people living with HIV (PLWH). The bone-derived hormone, undercarboxylated osteocalcin (ucOCN) regulates fat metabolism. We investigated the relationship between ucOCN change and body fat change among perimenopausal/postmenopausal HIV-seronegative and HIV-seropositive women on long-term antiretrovirals. Methods Perimenopausal and postmenopausal women enrolled in the Women's Interagency HIV Study (WIHS) MSK sub-study underwent trunk and total fat assessment via dual x-ray absorptiometry (DXA) at study enrollment (index visit) and again two years later. Circulating ucOCN and carboxylated osteocalcin (cOCN) were also measured at the index and two-year visits. The correlation between the two-year change in ucOCN and cOCN and change in trunk and total fat was assessed as a function of HIV-serostatus using linear regression modeling. Multivariate linear regression assessed the association between ucOCN and cOCN change and total and trunk fat change after adjusting for sociodemographic variables. Linear regression models restricted to HIV-seropositive women were performed to examine the contributions of HIV specific factors (index CD4 count, viral load, and cART use) on the associations. Results Increased ucOCN over the two-year follow-up was associated with less trunk and total fat accumulation in models adjusting for HIV-serostatus and participants sociodemographics, while there was no association with cOCN and the fat parameters. None of the HIV-specific factors evaluated influenced the association between ucOCN and fat parameters. Conclusion The current study suggests that increases in ucOCN are associated with decreased fat accumulation in HIV-seronegative and HIV-seropositive postmenopausal women on long-term antiretroviral therapy.

Introduction Aiming to reach UNAIDS 90‐90‐90 targets, nearly all sub‐Saharan African countries have expanded antiretroviral therapy (ART) to all people living with HIV (PLWH) (Treat All). Few published data exist on viral load testing and viral suppression under Treat All in this region. We assessed proportions of patients with available viral load test results and who were virally suppressed, as well as factors associated with viral suppression, among PLWH in 10 Rwandan health centres after Treat All implementation. Methods Cross‐sectional study during 2018 of adults (≥15 years) engaged in HIV care at 10 Rwandan health centres. Outcomes were being on ART (available ART initiation date in the study database, with no ART discontinuation prior to 1 January 2018), retained on ART (≥2 post‐ART health centre visits ≥90 days apart during 2018), available viral load test results (viral load measured in 2018 and available in study database) and virally suppressed (most recent 2018 viral load 49 years (adjusted prevalence ratio (aPR): 0.83, 95% CI 0.76 to 0.90 and those with pre‐ART CD4 counts of

Many recent studies have compared men currently taking pre-exposure prophylaxis (PrEP) to men not taking PrEP. However, less is known about demographic, behavioral, and geographic characteristics of men formerly, but not currently, taking PrEP. Using a 2017–2018 U.S. national, internet-based sample (n = 10,504) of men, transmen, and transwomen who have sex with men, we compared three groups based on their PrEP experiences. Results highlight individual-level financial and geo-contextual barriers to PrEP use that can inform prevention efforts to improve PrEP initiation and continuation for both PrEP-naive and PrEP-experienced individuals, respectively.

Background Women living with HIV (WLHIV) have lower rates of contraceptive use than noninfected peers, yet concerns regarding contraceptive efficacy and interaction with antiretroviral therapy (ART) complicate counseling. Hormonal contraceptives may increase genital tract HIV viral load (gVL) and sexual transmission risk to male partners. We compared gVL, plasma VL (pVL), and intrauterine contraceptive (IUC) continuation between the levonorgestrel intrauterine system (LNG-IUS) and copper intrauterine device (C-IUD) in Cape Town, South Africa. Methods and findings In this double-masked, randomized controlled noninferiority trial, eligible WLHIV were ages 18–40, not pregnant or desiring pregnancy within 30 months, screened and treated (as indicated) for reproductive tract infections (RTIs) within 1 month of enrollment, and virologically suppressed using ART or above treatment threshold at enrollment (non-ART). Between October 2013, and December 2016, we randomized consenting women within ART groups, using 1:1 permuted block randomization stratified by ART use, age (18–23, 24–31, 32–40), and recent injectable progestin contraceptive (IPC) exposure, and provided the allocated IUC. At all visits, participants provided specimens for gVL (primary outcome), pVL, RTI, and pregnancy testing. We assessed gVL and pVL across 6 and 24 months controlling for enrollment measures, ART group, age, and RTI using generalized estimating equation and generalized linear models (non-ART group pVL and hemoglobin) in as-treated analyses. We measured IUC discontinuation rates with Kaplan-Meier estimates and Cox proportional hazards models. We enrolled 71 non-ART (36 LNG-IUS, 31 C-IUD; 2 declined and 2 were ineligible) and 134 ART-using (65 LNG-IUS, 67 C-IUD; 1 declined and 1 could not complete IUC insertion) women. Participant median age was 31 years, and 95% had 1 or more prior pregnancies. Proportions of women with detectable gVL were not significantly different comparing LNG-IUS to C-IUD across 6 (adjusted odds ratio [AOR]: 0.78, 95% confidence interval [CI] 0.44–1.38, p = 0.39) and 24 months (AOR: 1.03, 95% CI: 0.68–1.57, p = 0.88). Among ART users, proportions with detectable pVL were not significantly different at 6 (AOR = 0.83, 95% CI 0.37–1.86, p = 0.65) and 24 months (AOR = 0.94, 95% CI 0.49–1.81, p = 0.85), whereas among non-ART women, mean pVL was not significantly different at 6 months (−0.10 log10 copies/mL, 95% CI −0.29 to 0.10, p = 0.50) between LNG-IUS and C-IUD users. IUC continuation was 78% overall; C-IUD users experienced significantly higher expulsion (8% versus 1%, p = 0.02) and elective discontinuation (adjusted hazard ratio: 8.75, 95% CI 3.08–24.8, p < 0.001) rates. Sensitivity analysis adjusted for differential IUC discontinuation found similar gVL results. There were 39 serious adverse events (SAEs); SAEs believed to be directly related to IUC use (n = 7) comprised 3 pelvic inflammatory disease (PID) cases and 4 pregnancies with IUC in place with no discernible trend by IUC arm. Mean hemoglobin change was significantly higher among LNG-IUS users across 6 (0.57 g/dL, 95% CI 0.24–0.90; p < 0.001) and 24 months (0.71 g/dL, 95% CI 0.47–0.95; p < 0.001). Limitations included not achieving non-ART group sample size following change in ART treatment guidelines and truncated 24 months’ outcome data, as 17 women were not yet eligible for their 24-month visit at study closure. Also, a change in VL assay during the study may have caused some discrepancy in VL values because of different limits of detection. Conclusions In this study, we found that the LNG-IUS did not increase gVL or pVL and had low levels of contraceptive failure and associated PID compared with the C-IUD among WLHIV. LNG-IUS users were significantly more likely to continue IUC use and had higher hemoglobin levels over time. The LNG-IUS appears to be a safe contraceptive with regard to HIV disease and may be a highly acceptable option for WLHIV. Trial registration ClinicalTrials.gov NCT01721798., Catherine Todd and colleagues study an intrauterine contraceptive device in women with HIV infection., Author summary Why was this study done? Women living with HIV (WLHIV) infection must consider their contraceptive options in tandem with and complicated by potential interactions between hormonal contraception and HIV disease. These issues potentially contribute to lower use of highly effective hormonal contraceptive methods among WLHIV. Global use of intrauterine contraception (IUC), specifically the levonorgestrel intrauterine system (LNG-IUS), has increased across the last decade. However, there are few trials comparing safety of the LNG-IUS with that of the copper intrauterine device (C-IUD) among WLHIV and none focusing specifically on impact on HIV disease. What did the researchers do and find? In a randomized controlled trial in Cape Town, South Africa, 199 women with confirmed HIV seropositivity and not desiring pregnancy in the next 30 months were recruited and allocated, with 98 receiving the C-IUD and 101 the LNG-IUS. Participants had genital tract samples collected by menstrual cup and blood taken for genital and plasma viral load levels at enrollment and at 3-, 6-, 12-, 18-, and 24-month visits. Women could return at any time for unscheduled visits and remained in the study even if the IUC was removed on request. Women receiving the LNG-IUS did not have any significant difference in change in detectable genital tract viral load compared with C-IUD users, regardless of ART status. However, women receiving the C-IUD were more likely to have the IUC removed than those receiving the LNG-IUS through the study period. What do these findings mean? This study is among the first comparing a hormonal to nonhormonal long-acting reversible contraceptive method with genital tract HIV RNA as the primary outcome among WLHIV. These data suggest that LNG-IUS is as safe as the C-IUD for WLHIV and will strengthen international medical eligibility guidelines. The high continuation rates of the LNG-IUS, critically important for a device with a 5-year duration of use, should prompt including this method in the available method mix to promote the ability of WLHIV to meet their fertility goals.

Introduction Foreign‐born persons comprise ~13% of the US population. Immigrants, especially women, often face a complex set of social and structural factors that negatively impact health outcomes including greater risk of HIV infection. We described socio‐demographic, clinical and immunological characteristics and AIDs and non‐AIDS death among foreign‐born women living with HIV (FBWLWH) participating in the US Women’s Interagency HIV Study (WIHS) in the US from 1994 to 2016. We hypothesized that FBW will experience higher AIDS‐related mortality compared to US‐born women (USBW). Methods The WIHS is a multicenter prospective observational cohort study of mostly women living with HIV (WLWH). The primary exposure in this analysis, which focused on 3626 WLWH, was self‐reported country of birth collapsed into foreign‐born and US born. We assessed the association of birthplace with categorized demographic, clinical and immunological characteristics, and AIDS/non‐AIDS mortality of WLWH, using chi‐squared tests. Proportional hazard models examined the association of birthplace with time from enrolment to AIDS and non‐AIDS death. Results Of the 628 FBW, 13% were born in Africa, 29% in the Caribbean and 49% in Latin America. We observed significant differences by HIV status in socio‐demographic, clinical and immunological characteristics and mortality. For both AIDS and non‐AIDS caused deaths FBW WLWH had lower rates of death. Adjusting for year of study enrolment and other demographic/clinical characteristics mitigated FBW’s statistical survival advantage in AIDS deaths Relative Hazard (RH = 0.91 p = 0.53), but did not substantively change the survival advantage in non‐AIDS deaths RH = 0.33, p

Purpose To estimate time from seroconversion to diagnosis, researchers have modeled time based on CD4 decline, assuming the square root of the CD4 count decreases linearly over time before antiretroviral treatment (ART) initiation. If true, utilizing CD4 counts reported anytime in the pre-ART period would result in estimates of diagnosis delay that are not appreciably different. Methods We applied CD4 depletion model parameters from seroconverter cohorts to New York City residents diagnosed from 2006 to 2015, having two or more pre-ART CD4 counts. Results Median diagnosis delays based on first or second pre-ART CD4 counts were similar (n = 12,849; 2.8 years, interquartile range [IQR]: 0–7.7, and 2.8 years, IQR: 0–7.6, respectively; P = .09, Wilcoxon signed-rank test). Among people whose second pre-ART CD4 count was measured more than 6 months after diagnosis (n = 2761), the average diagnosis delay based on first pre-ART CD4 count was shorter (1.5 years, IQR: 0–5.4) than the second pre-ART CD4 count (1.7 years, IQR: 0–6.0) but not significantly (P = .12). Conclusions Results are consistent with the linearity assumption of the CD4 depletion model. To estimate population-level diagnosis delay, researchers may use pre-ART CD4 counts reported more than 6 months post-diagnosis.

Young black men and transgender women (transwomen) who have sex with men or transwomen are most vulnerable in terms of risk for HIV infection, also reflected in their extremely high incidence rates. As testing rates and pre-exposure prophylaxis (PrEP) uptake remain suboptimal among these groups, primarily due to unique structural barriers, the present analyses draw on data from an online survey, administered October 2014 to August 2015, to explore social support–related predictors of knowledge and behavior around HIV prevention. Participants were 169 biological men who identified as black, with a mean age of 24 (SD = 2.97, range 17–29); 8% identified as transwomen. Logistic regression models assessed whether HIV-related social support predicted HIV testing patterns, PrEP awareness, and use. Those with higher HIV-related social support reported having been more likely to have ever tested (adjusted odds ratio (aOR) = 1.48; p < 0.001) and tested in the past 6 months (aOR = 1.22; p < 0.01). They were also more likely to intend to test in the next 6 months (aOR = 1.16; p < 0.001), including at a medical office or community-based organization (aOR = 1.20; p < 0.001), yet less likely to intend to self-test (aOR = 0.81; p < 0.001). Lastly, higher social support was significantly associated with prior knowledge of self-testing (aOR = 1.19; p < 0.05), couples testing (aOR = 1.26; p < 0.001), and PrEP (aOR = 1.22; p < 0.01), as well as prevention self-efficacy (aOR = 1.30; p < 0.001), but inversely associated with prior self-testing (aOR = 0.80; p < 0.05). For young black men and transwomen who have sex with men or transwomen, HIV-related social support, which likely has a strong peer component, appears to be a facilitator of optimal testing and intentions to test, as well as awareness of novel prevention strategies (like self-testing or PrEP). However, community resourcefulness needs to be bolstered by other mechanisms, such as changes within healthcare settings, to increase actual use of novel prevention modalities.

Background HIV testing is critical to HIV prevention and care. Infrequent HIV testing and late HIV diagnosis have been observed among young Black men who have sex with men and transwomen. Novel interventions to increase HIV testing rates among young Black men who have sex with men and transwomen are needed. Methods A randomized controlled trial among 236 young Black men and transwomen who have sex with men or transwomen evaluated the efficacy of an intervention that included completion of a brief survey and receipt of a personalized recommendation of an optimal HIV testing approach. Participants completed a computerized baseline assessment and were randomized to electronically receive either a personalized recommendation or standard HIV testing information. Follow-up surveys were conducted online at 3 and 6 months. Results Retention was 92% and 93% at 3-month and 6-month follow-up, respectively. At baseline, 41% of participants reported that they tested for HIV in the past 3 months and another 25% between 4 and 6 months ago. Intent-to-treat analyses found that participants randomized to the experimental arm (personalized recommendation) were not significantly more likely to test for HIV compared with participants in the standard HIV testing information control arm at 3 months (76% vs. 71%; P = 0.40) and 6 months (73% vs. 72%; P = 0.81), respectively. Conclusions This study evaluated an innovative intervention to increase HIV testing by matching individuals to optimal HIV testing approaches. Participants in both arms increased past 3-month HIV testing, suggesting that providing information on options and/or raising risk awareness is sufficient to significantly increase HIV testing. Trial registration ClinicalTrial.gov NCT02834572 https://clinicaltrials.gov/ct2/show/NCT02834572.

Objectives African women are disproportionately affected by HIV infection and may experience non-AIDS-related complications associated with inflammation. High-sensitivity C-reactive protein (hsCRP), d-dimer and transthyretin have been examined as inflammatory markers elsewhere, but it is unclear how they change over time in HIV-negative or HIV-positive African women with or without antiretroviral therapy (ART) initiation. Methods We examined hsCRP, d-dimer and transthyretin levels at baseline and at follow-up of ≥2 years in 185 HIV-negative and 510 HIV-positive Rwandan women who were ART naive at study entry. Generalized estimating equations for each marker were used to investigate the association with HIV infection/CD4 count, ART and follow-up time. Results Compared with HIV-negative women, HIV-positive women had higher hsCRP and d-dimer and lower transthyretin concentrations, with greater differences at lower CD4 counts. After adjusting for CD4 count and other factors, ART was not significantly associated with log hsCRP (P = 0.36) at follow-up, but was independently associated with lower log d-dimer (P = 0.03) and higher transthyretin (P = 0.0008) concentrations. At ≥ 2 years of follow-up, hsCRP had not significantly changed in any group but log d-dimer had decreased significantly in all groups. Transthyretin declined significantly over time in HIV-negative women and HIV-positive non-ART initiators, but increased significantly in HIV-positive ART initiators. Conclusions HIV infection and advanced immune suppression were associated with higher hsCRP and d-dimer and lower transthyretin concentrations. ART (independently of CD4 changes) was significantly associated with decreases in d-dimer and increases in transthyretin, but, in contrast to other studies, was not associated with decreases in hsCRP. We found no change in hsCRP over time in any group.

BACKGROUND: Data on associations between abdominal fat depot mass and subclinical atherosclerosis are limited, especially in women with HIV. METHODS: We assessed cross-sectional associations of dual X-ray absorptiometry scan-derived estimates of visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) with 3 measures of subclinical carotid artery atherosclerosis-- carotid artery stiffness (Young’s modulus of elasticity), presence of carotid artery lesions, and carotid artery intima-media thickness (cIMT)-- in a subsample of participants in the Women’s Interagency HIV Study. Statistical models adjusted for demographic variables, HIV serostatus, behavioral variables, and cardiovascular risk factors. RESULTS: There were 244 women with and 99 without HIV infection (median age 42, 62% black). VAT mass (but not SAT) was associated with greater carotid artery stiffness in a fully adjusted linear regression model, including adjustment for SAT (β = 11.3 log 10(3) N*M(−2) per kg VAT, 95% confidence interval [1.0, 21.7]). Greater SAT mass was associated with lower odds of having a carotid artery lesion in a fully adjusted model, including adjustment for VAT (adjusted odds ratio, 0.49 per kg of SAT [0.25, 0.94]). Neither VAT nor SAT was associated with cIMT. The VAT/SAT ratio was not statistically associated with any of the outcomes after covariate adjustment. CONCLUSIONS: In our cross-sectional study of women, the majority of whom had HIV, greater VAT mass was associated with increased carotid artery stiffness whereas greater SAT mass was associated with a reduced odds of prevalent carotid artery lesions.

OBJECTIVE: To determine if adjusted mortality, walking ability or return home differed after hip fracture surgery between Canada and the USA. DESIGN: Secondary analysis of the Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS) trial data. SETTING: Data were collected from 47 American and Canadian hospitals. PARTICIPANTS: Overall, 2016 subjects with a hip fracture (USA = 1222 (60.6%); Canada = 794 (39.4%)) were randomized to a liberal or restrictive transfusion strategy. Subjects were 50 years and older, with cardiovascular disease and/or risk factors and hemoglobin

Objective The aim of this study was to determine the associations between visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) mass with homeostatic model assessment-insulin resistance (HOMA-IR) and incidence of diabetes mellitus in women with and without HIV infection. Design Cross-sectional design for associations between abdominal fat and HOMA-IR; longitudinal design for associations between abdominal fat and incident diabetes. Methods We assessed associations between dual X-ray absorptiometry scan-derived VAT and SAT with HOMA-IR in a subsample from the Women's Interagency HIV Study (n = 226 with and n = 100 without HIV) using linear regression. We evaluated associations of VAT, SAT and HOMA-IR with incident diabetes mellitus using Cox proportional hazards models. Results VAT mass was positively associated with log HOMA-IR in fully adjusted linear regression models stratified by HIV serostatus, including adjustment for SAT. During median follow-up of 10.6 years, incidence of diabetes was 1.63 [95% confidence interval (95% CI) 1.15-2.31] and 1.32 [95% CI 0.77-2.28] cases per 100 person-years in women with and without HIV (P = 0.52). In a fully adjusted model, baseline VAT (hazard ratio 2.64 per kg; 95% CI 1.14-6.12; P = 0.023) and SAT (hazard ratio 1.34 per kg; 95% CI 0.73-2.45; P = 0.35) were associated with incident diabetes, but the latter was not statistically significant. Conclusion VAT mass was independently associated with HOMA-IR in women with and without HIV and was independently associated with future development of diabetes.

Pain is frequent and underreported among HIV+ women. We determined occurrence and severity of pain, and types of pain treatments used among HIV+ and HIV− women. Cross-sectional analyses of pain as measured by the Brief Pain Inventory Short Form, and related pain therapies nested in the Women’s Interagency HIV Study (WIHS). Multiple variable linear regression models examined differences by HIV status in pain severity and pain interference in general activity, mood, ability to walk, work, relationships with others, sleep, and enjoyment of life. Among 1393 HIV+ and 587 HIV− participants with median age 47–48 years, there was no statistically significant difference in pain reported within the past week by HIV status (HIV+ 50% vs. 49% HIV−, p = 0.70). Ratings of pain severity and interference were similar between HIV+ and HIV− women, as was receipt of pain medication (58% HIV+ vs. 56% HIV−). Pain medications most frequently used were: NSAIDS (90% HIV+, 96% HIV−), opioids (65% HIV+, 67% HIV−), topical anesthetics (46% HIV+, 56% HIV−), muscle relaxants (23% HIV+, 14% HIV−), and anticonvulsants (23% HIV+, 14% HIV−). Nearly half of predominantly low income, minority women reported pain in the past week, and two-thirds reported opioid use for pain management. The occurrence, severity, and treatment of pain did not differ by HIV status, nor did report of pain interference with mood or function. Additional research is needed to better characterize pain etiology among HIV+ women in the era of potent antiretroviral therapy, and determine the extent to which pain severity and type of medication used for pain treatment impact HIV disease outcomes.

Summary Background Blood transfusion might affect long-term mortality by changing immune function and thus potentially increasing the risk of subsequent infections and cancer recurrence. Compared with a restrictive transfusion strategy, a more liberal strategy could reduce cardiac complications by lowering myocardial damage, thereby reducing future deaths from cardiovascular disease. We aimed to establish the effect of a liberal transfusion strategy on long-term survival compared with a restrictive transfusion strategy. Methods In the randomised controlled FOCUS trial, adult patients aged 50 years and older, with a history of or risk factors for cardiovascular disease, and with postoperative haemoglobin concentrations lower than 100 g/L within 3 days of surgery to repair a hip fracture, were eligible for enrolment. Patients were recruited from 47 participating hospitals in the USA and Canada, and eligible participants were randomly allocated in a 1:1 ratio by a central telephone system to either liberal transfusion in which they received blood transfusion to maintain haemoglobin level at 100 g/L or higher, or restrictive transfusion in which they received blood transfusion when haemoglobin level was lower than 80 g/L or if they had symptoms of anaemia. In this study, we analysed the long-term mortality of patients assigned to the two transfusion strategies, which was a secondary outcome of the FOCUS trial. Long-term mortality was established by linking the study participants to national death registries in the USA and Canada. Treatment assignment was not masked, but investigators who ascertained mortality and cause of death were masked to group assignment. Analyses were by intention to treat. The FOCUS trial is registered with ClinicalTrials.gov, number NCT00071032. Findings Between July 19, 2004, and Feb 28, 2009, 2016 patients were enrolled and randomly assigned to the two treatment groups: 1007 to the liberal transfusion strategy and 1009 to the restrictive transfusion strategy. The median duration of follow-up was 3·1 years (IQR 2·4–4·1 years), during which 841 (42%) patients died. Long-term mortality did not differ significantly between the liberal transfusion strategy (432 deaths) and the restrictive transfusion strategy (409 deaths) (hazard ratio 1·09 [95% CI 0·95–1·25]; p=0·21). Interpretation Liberal blood transfusion did not affect mortality compared with a restrictive transfusion strategy in a high-risk group of elderly patients with underlying cardiovascular disease or risk factors. The underlying causes of death did not differ between the trial groups. These findings do not support hypotheses that blood transfusion leads to long-term immunosuppression that is severe enough to affect long-term mortality rate by more than 20–25% or cause of death. Funding National Heart, Lung, and Blood Institute.

BACKGROUND Initiation of antiretroviral therapy (ART) in the advanced stages of HIV infection remains a major challenge in sub-Saharan Africa. This study was conducted to better understand barriers and enablers to timely ART initiation in Rwanda where ART coverage is high and national ART eligibility guidelines first expanded in 2007-2008. METHODS Using data on 6326 patients (≥15 years) at five Rwandan clinics, we assessed trends and correlates of CD4 cell count at ART initiation and the proportion initiating ART with advanced HIV disease (CD4

It is not well understood how infection with HIV and prior experience of sexual violence affects sexual behavior in African women. We describe factors influencing current sexual practices of Rwandan women living with or without HIV/AIDS. By design, 75 % of participants were HIV positive and ~50 % reported having experienced genocidal rape. Univariate and multivariate logistic regression models were fit to describe demographic and clinical characteristics that influenced sexual behavior in the previous 6 months, condom use, history of transactional sex, and prior infection with a non-HIV sexually transmitted disease. Respondents' age, where they lived, whether or not they lived with a husband or partner, experience of sexual trauma, CD4 count, CES-D and PTSD scores were strongly associated with risky sexual behavior and infection with non-HIV STI. HIV positive women with a history of sexual violence in the contexts of war and conflict may be susceptible to some high-risk sexual behaviors.

For women, the high-risk sex script of condomless sex to maintain relationships with men is concerning, particularly in regard to heterosexual HIV acquisition. This secondary analysis of data from a clinical trial evaluated the effect of a 12-episode, web-based video series intervention, entitled Love, Sex, and Choices, versus a text message control on lowering the high-risk sex script. The sample comprised 238 predominately urban Black women, ages 18-29, having HIV sex risk behavior. Data were collected at baseline and 6 months post-intervention. The Sex Script Video Response score was used to measure a high-risk sex script. HIV sex risk behavior was measured by Vaginal Equivalent Episodes with high-risk partners. At baseline, lower education, younger age at first sexual intercourse, and alcohol/non-injection drug use before sex were positively associated with a high-risk sex script. At baseline, as the high-risk sex script increased by one log unit, sex risk behavior increased by 0.47 log units (p < 0.001), equivalent to a 60% increase in the geometric mean of sex risk behavior. ANCOVA analysis indicated that from baseline to 6-months post intervention, lowering the high-risk sex script by one unit was associated with an additional reduction of 0.26 units in sex risk behavior. Compared to the text messages, the LSC video series was associated with a 27% greater reduction in the geometric mean of the sex script (p = 0.03). Further investigation into the effect of lowering sex scripts to reduce sex risk behavior is recommended.

Background 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. Methods 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). Results 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). Conclusions 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.

Objectives Predicting mortality in middle-aged HIV-infected (HIV+) women on antiretroviral therapies (ART) is important for understanding the impact of HIV infection. Several health indices have been used to predict mortality in women with HIV infection. We evaluated: (1) an HIV biological index, Veterans Aging Cohort Study (VACS); (2) a physical index, Fried Frailty Index (FFI); and (3) a mental health index, Center for Epidemiologic Studies-Depression (CES-D). Proportional hazards regression analyses were used to predict death and included relevant covariates. Design Prospective, observational cohort. Setting Multicentre, across six sites in the USA. Participants 1385 multirace/ethnic ART-experienced HIV+ women in 2005. Primary and secondary outcomes All deaths, AIDS deaths and non-AIDS deaths up to ~8 years from baseline. Results Included together in one model, VACS Index was the dominant, significant independent predictor of all deaths within 3 years (HR=2.20, 95% CI 1.83, 2.65, χ2=69.04, p

Problem How does menstrual cup (MC) compare to other genital sampling methods for HIV RNA recovery? Method of study We compared HIV RNA levels between MC, endocervical swab (ECS), and ECS-enriched cervicovaginal lavage (eCVL) specimens in 51 HIV-positive, antiretroviral therapy-naive women at enrollment, 3 and 6 months, with order rotated by visit. Paired comparisons were analyzed with McNemar's exact tests, signed-rank tests, and an extension of Somer's D for pooled analyses across visits. Results MC specimens had the highest proportion of quantifiable HIV VL at enrollment and month 3, but more MC specimens (n=12.8%) were insufficient for testing, compared with ECS (2%, P=0.006) and eCVL (0%, P

BackgroundDespite the World Health Organization (WHO) regularly updating guidelines to recommend earlier initiation of antiretroviral therapy (ART) in children, timely enrollment into care and initiation of ART in sub-Saharan Africa in children lags behind that of adults. The impact of implementing increasingly less restrictive ART guidelines on ART initiation in Central Africa has not been described.Materials and methodsData are from the Central Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) pediatric cohort of 3,426 children (0-15 years) entering HIV care at 15 sites in Burundi, DRC, and Rwanda. Measures include CD4 count, WHO clinical stage, age, and weight-for-age Z score (WAZ), each at enrollment into HIV care and at ART initiation. Changes in the medians or proportions of each measure by year of enrollment and year of ART initiation were assessed to capture potential impacts of changing ART guidelines.ResultsMedian age at care enrollment decreased from 77.2 months in 2004-05 to 30.3 months in 2012-13. The median age at ART initiation (n = 2058) decreased from 83.0 months in 2004-05 to 66.9 months in 2012-13. The proportion of children ≤24 months of age at enrollment increased from 12.7% in 2004-05 to 46.7% in 2012-13, and from 9.6% in 2004-05 to 24.2% in 2012-13 for ART initiation. The median CD4 count at enrollment into care increased from 563 (IQR: 275, 901) in 2004-05 to 660 (IQR: 339, 1071) cells/μl in 2012-13, and the median CD4 count at ART initiation increased from 310 (IQR:167, 600) in 2004-05 to 589 (IQR: 315, 1113) cells/μl in 2012-13. From 2004-05 to 2012-13, median WAZ improved from -2 (IQR: -3.4, -1.1) to -1 (IQR: -2.5, -0.2) at enrollment in care and from -2 (IQR: -3.8, -1.6) to -1 (IQR: -2.6, -0.4) at ART initiation.Discussion and conclusionAlthough HIV-infected children ≤24 months of age accounted for half of all children enrolling in care in our cohort during 2012-13, they represented less than a quarter of all those who were initiated on ART during the same period. Further research is needed to identify barriers to timely diagnosis, linkage to care, and initiation of ART among children with HIV infection.

BackgroundReproductive aging may impact the vaginal microbiome and genital tract mucosal immune environment and contribute to genital tract health in women living with and at-risk for HIV infection.MethodsA cross-sectional study of 102 HIV+ (51 premenopausal, 51 postmenopausal) and 39 HIV-uninfected (HIV-) (20 premenopausal, 19 postmenopausal) women was performed in Bronx and Brooklyn, NY. Cervicovaginal lavage (CVL) was collected for quantification of innate antimicrobial activity against E. coli, HSV-2 and HIV and immune mediators by Luminex and ELISA. Microbiome studies by qPCR and 16S rRNA sequencing were performed on vaginal swabs.ResultsHIV+ postmenopausal compared to premenopausal participants had lower median E. coli bactericidal activity (41% vs. 62%, p = 0.001), lower median gene copies of Lactobacillus crispatus (p = 0.005) and Lactobacillus iners (p = 0.019), lower proportions of Lactobacillus iners, higher proportions of Gardnerella and Atopobium vaginae and lower levels of human beta defensins (HBD-2, HBD-3) and secretory leukocyte protease inhibitor (SLPI), pConclusionsHIV+ postmenopausal compared to premenopausal participants have less CVL E. coli bactericidal activity, reflecting a reduction in Lactobacilli and a greater proportion of Gardnerella and A. vaginae, and more HSV-2 inhibitory activity, reflecting increased mucosal inflammation. The effect of menopause on mucosal immunity was greater in HIV+ participants, suggesting a synergistic impact. Promotion of a lactobacillus dominant vaginal microbiome and reduced mucosal inflammation may improve vaginal health and reduce risk for shedding of HIV and potential for HIV transmission in HIV+ menopausal women.

Objective: To assess the association of race with clinical outcomes in HIV-positive women on continuous HAART. Design: Prospective study that enrolled women from 1994 to 1995 and 2001 to 2002. Setting: Women's Interagency HIV Study, a community-based cohort in five US cities. Participants: One thousand, four hundred and seventy-one HIV-positive continuous HAART users. Main outcome measures: Times to AIDS and non-AIDS death and incident AIDS-defining illness (ADI) after HAART initiation. Results: In adjusted analyses, black vs. white women had higher rates of AIDS death [adjusted hazard ratio (aHR) 2.14, 95% confidence interval (CI) 1.30, 3.50; P = 0.003] and incident ADI (aHR 1.58, 95% CI 1.08, 2.32; P = 0.02), but not non-AIDS death (aHR 0.91, 95% CI 0.59, 1.39; P = 0.65). Cumulative AIDS death incidence at 10 years was 17.3 and 8.3% for black and white women, respectively. Other significant independent pre-HAART predictors of AIDS death included peak viral load (aHR 1.70 per log10, 95% CI 1.34, 2.16; P

We examined whether established associations between HIV disease and HIV disease progression on worse health-related quality of life (HQOL) were applicable to women with severe trauma histories, in this case Rwandan women genocide survivors, the majority of whom were HIV-infected. Additionally, this study attempted to clarify whether post-traumatic stress symptoms were uniquely associated with HQOL or confounded with depression.The Rwandan Women's Interassociation Study and Assessment was a longitudinal prospective study of HIV-infected and uninfected women. At study entry, 922 women (705 HIV+ and 217 HIV-) completed measures of symptoms of post-traumatic stress and HQOL as well as other demographic, clinical, and behavioral characteristics.Even after controlling for potential confounders and mediators, HIV+ women, in particular those with the lowest CD4 counts, scored significantly worse on HQOL and overall quality of life (QOL) than did HIV- women. Even after controlling for depression and HIV disease progression, women with more post-traumatic stress symptoms scored worse on HQOL and overall QOL than women with fewer post-traumatic stress symptoms.This study demonstrated that post-traumatic stress symptoms were independently associated with HQOL and overall QOL, independent of depression and other confounders or potential mediators. Future research should examine whether the long-term impact of treatment on physical and psychological symptoms of HIV and post-traumatic stress symptoms would generate improvement in HQOL.

Background To determine the frequency and risk factors for falls among middle-aged HIV+ and HIV- women in the Women's Interagency HIV Study (WIHS). Methods 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). Results 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 Conclusions 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.

The role men who have sex with men and women (MSMW) play in heterosexual HIV transmission is not well understood. We analyzed baseline data from Project MIX, a behavioral intervention study of substance-using men who have sex with men (MSM), and identified correlates of unprotected vaginal intercourse, anal intercourse, or both with women (UVAI). Approximately 10 % (n = 194) of the men reported vaginal sex, anal sex, or both with a woman; of these substance-using MSMW, 66 % (129) reported UVAI. Among substance-using MSMW, multivariate analyses found unemployment relative to full/part-time employment (OR = 2.28; 95 % CI 1.01, 5.17), having a primary female partner relative to no primary female partner (OR = 3.44; CI 1.4, 8.46), and higher levels of treatment optimism (OR = 1.73; 95 % CI 1.18, 2.54) increased odds of UVAI. Strong feelings of connection to a same-race gay community (OR = 0.71; 95 % CI 0.56, 0.91) and Viagra use (OR = 0.31; 95 % CI 0.10, 0.95) decreased odds of UVAI. This work suggests that although the proportion of substance-using MSM who also have sex with women is low, these men engage in unprotected sex with women, particularly with primary female partners. This work highlights the need for further research with the substance using MSMW population to inform HIV prevention interventions specifically for MSMW.

First-line antiretroviral treatment regimens in resource-limited settings used in breastfeeding mothers often include stavudine (d4T). Limited data describing d4T concentrations in breast milk are available. We analyzed d4T concentrations in 52 mother-infant pairs using ultra-performance liquid chromatography-tandem mass spectrometry (lower limit of quantification: 5 ng/mL in plasma, 20 ng/mL in breast milk). Median (interquartile range) d4T concentrations were 86 (36-191) ng/mL in maternal plasma, 151 (48-259) ng/mL in whole milk, 190 (58-296) ng/mL in skim milk, and5 (5 to5) ng/mL in infant plasma. Although d4T is concentrated in breast milk relative to maternal plasma, the infant d4T dose received from breast milk is very small and not clinically significant.

The objectives of this cross-sectional study were to compare sociodemographic and risk behavior characteristics between black men who have sex with both men and women (MSMW) and those who have sex with men only (MSMO) and assess factors associated with having any unprotected vaginal and/or anal intercourse (UVAI) with women in the last 3 months. Data from 326 black men who reported recent unprotected anal intercourse with a man in an HIV behavioral intervention study in New York City were analyzed. Baseline characteristics were compared between MSMW and MSMO, and factors associated with having any UVAI in the past 3 months with women among MSMW were evaluated. In total, 26.8% reported having sex with both men and women in the last 3 months. MSMW were less likely to be HIV infected, use amyl nitrates, and have unprotected receptive anal sex with most recent male partner. MSMW were more likely to be over 40 years old and use heroin. A total of 55.6% of MSMW reported having UVAI with women in the last 3 months. Compared to MSMW having only protected sex, MSMW having any UVAI with women were less likely to be HIV infected and to disclose having sex with men to female partners; they were more likely to have greater than four male sex partners in the last 3 months. In conclusion, HIV prevention interventions among black MSMW should directly address the risk of HIV transmission to both their female and male partners. Disclosure of bisexuality to female partners may be an important component of future prevention efforts.

Objectives: We investigate, among older adult nursing home residents diagnosed with depression, whether depression treatment differs by race and schooling, and whether differences by schooling differ by race. We examine whether Blacks and less educated residents are placed in facilities providing less treatment, and whether differences reflect disparities in care. Method: Data from the 2006 Nursing Home Minimum Data Set for 8 states ( n = 124,431), are merged with facility information from the Online Survey Certification and Reporting system. Logistic regressions examine whether resident and/or facility characteristics explain treatment differences; treatment includes antidepressants and/or psychotherapy. Results: Blacks receive less treatment (adj. OR = .79); differences by education are small. Facilities with more Medicaid enrollees, fewer high school graduates, or more Blacks provide less treatment. Discussion: We found disparities at the resident and facility level. Facilities serving a low-SES (socioeconomic status), minority clientele tend to provide less depression care, but Blacks also receive less depression treatment than Whites within nursing homes (NHs).

ObjectivesThe incidence of fractures appears to be increased in HIV-infected individuals.MethodsWe assessed bone quality using quantitative ultrasound (QUS) in HIV-infected and uninfected Rwandan women. A Sunlight Omnisense 7000 QUS was used to measure the speed of ultrasound (SOS) at the distal radius in 646 antiretroviral therapy (ART)-naive HIV-infected women and 211 HIV-uninfected women. The Z-scores for SOS were based on data for women of the same age from the manufacturer's reference material.ResultsThe mean CD4 cell count was 285 (+/- 166) cells/mu L in the HIV-positive women. SOS Z-scores adjusted and unadjusted for body mass index did not differ between the groups. SOS did not differ by CD4 count ( = 200 cells/mu L: 4016 (+/- 117) vs. 4028 (+/- 107) m/s, respectively; p=0.19.ConclusionsIn HIV-positive ART-naive Rwandan women with advanced HIV disease, bone quality at the distal radius was similar to that in HIV-negative controls.

Depression and posttraumatic stress disorder (PTSD) are common in developing and postconflict countries. The purpose of this study is to examine longitudinal changes in PTSD in HIV-infected and uninfected Rwandan women who experienced the 1994 genocide.Five hundred thirty-five HIV-positive and 163 HIV-negative Rwandan women in an observational cohort study were followed for 18 months. Data on PTSD symptoms were collected longitudinally by the Harvard Trauma Questionnaire (HTQ) and analyzed in relationship to demographics, HIV status, antiretroviral treatment (ART), and depression. PTSD was defined as a score on the HTQ of ≥2.There was a continuing reduction in HTQ scores at each follow-up visit. The prevalence of PTSD symptoms changed significantly, with 61% of the cohort having PTSD at baseline vs. 24% after 18 months. Women with higher HTQ score were most likely to have improvement in PTSD symptoms (p0.0001). Higher rate of baseline depressive symptoms (p0.0001) was associated with less improvement in PTSD symptoms. HIV infection and ART were not found to be consistently related to PTSD improvement.HIV care settings can become an important venue for the identification and treatment of psychiatric problems affecting women with HIV in postconflict and developing countries. Providing opportunities for women with PTSD symptoms to share their history of trauma to trained counselors and addressing depression, poverty, and ongoing violence may contribute to reducing symptoms.

Optimizing the survival of HIV-uninfected infants born to HIV-infected mothers (ie, HIV-exposed infants) is a major challenge in sub-Saharan Africa, where prevalence of HIV infection remains high among reproductive-age women [1]. The detrimental effects of early weaning to prevent HIV transmission have been shown in multiple studies from Malawi, Uganda, and Botswana [2–5]. In these studies, the risk of severe gastroenteritis and mortality associated with gastroenteritis were higher among HIV-exposed but uninfected infants who were weaned early (at 4–6 months of age), compared with those who breastfed (BF) for longer periods. Additional adverse effects of nonbreastfeeding (NBF) or early weaning among HIV-uninfected African children include acute malnutrition, such as marasmus and kwashiorkor [5], and growth faltering [6, 7]. Infants who stopped BF also did not show increases in HIV-free survival (ie, both remaining alive and free of HIV infection) [8, 9]. How to balance the risks and benefits of BF of HIV-uninfected children of HIV-infected mothers in resource-constrained settings of sub-Saharan Africa where BF alternatives are not safe has been extensively discussed [10–12]. The recent World Health Organization (WHO) recommendations on infant feeding and HIV emphasize infant HIV-free survival [13]. Despite the evidence that NBF increases infant morbidity and mortality in resource-constrained settings, our understanding of the timing of these adverse events is limited. For clinical management and program planning, it will be valuable to know immediate and long-term effects of weaning whenever this practice is initiated. We hypothesize that cessation of BF to prevent transmission of HIV leads to early acute morbidity that occurs during the process of weaning or immediately after weaning. However, infant mortality associated with weaning is a late effect and occurs after the weaning process is completed. The aim of this study was to determine, among HIV-exposed, uninfected Malawian infants, morbidity rates in short follow-up intervals (∼3 months) that encompass weaning and to assess cumulative rates of mortality over time. These infants were originally enrolled in the extended antiretroviral Post-exposure Prophylaxis of Infants in Malawi (PEPI-Malawi) trial.