Treatment of IDH-mutant glioma in the INDIGO era.

Gliomas are the most common primary brain tumor and are uniformly lethal. Despite significant advancements in understanding the genetic landscape of gliomas, standard-of-care has remained largely unchanged. Subsets of gliomas are defined by gain-of-function mutations in the metabolic genes encoding isocitrate dehydrogenase (IDH). Efforts to exploit mutant IDH activity and/or directly inhibit it with mutant IDH inhibitors have been the focus of over a decade of research. The recently published INDIGO trial, demonstrating the benefit of the mutant IDH inhibitor vorasidenib in patients with low-grade IDH-mutant gliomas, introduces a new era of precision medicine in brain tumors that is poised to change standard-of-care. In this review, we highlight and contextualize the results of the INDIGO trial and introduce key questions whose answers will guide how mutant IDH inhibitors may be used in the clinic. We discuss possible combination therapies with mutant IDH inhibition and future directions for clinical and translational research.

Human Immunodeficiency Virus and Hepatitis C Virus-related Disparities in Undergoing Emergency General Surgical Procedures in the United States, 2016-2019.

OBJECTIVE: To determine whether people living with human immunodeficiency virus (PLWHIV) and people living with hepatitis C virus (PLWHCV) experience inequities in receipt of emergency general surgery (EGS) care. BACKGROUND: PLWHIV and PLWHCV face discrimination in many domains; it is unknown whether this extends to the receipt of EGS care. METHODS: Using data from the 2016 to 2019 National Inpatient Sample, we examined 507,458 nonelective admissions of adults with indications for one of the 7 highest-burden EGS procedures (partial colectomy, small-bowel resection, cholecystectomy, operative management of peptic ulcer disease, lysis of peritoneal adhesions, appendectomy, or laparotomy). Using logistic regression, we evaluated the association between HIV/HCV status and the likelihood of undergoing one of these procedures, adjusting for demographic factors, comorbidities, and hospital characteristics. We also stratified analyses for the 7 procedures separately. RESULTS: After adjustment for covariates, PLWHIV had lower odds of undergoing an indicated EGS procedure [adjusted odds ratio (aOR): 0.81; 95% CI: 0.73-0.89], as did PLWHCV (aOR: 0.66; 95% CI: 0.63-0.70). PLWHIV had reduced odds of undergoing cholecystectomy (aOR: 0.68; 95% CI: 0.58-0.80). PLWHCV had lower odds of undergoing cholecystectomy (aOR: 0.57; 95% CI: 0.53-0.62) or appendectomy (aOR: 0.76; 95% CI: 0.59-0.98). CONCLUSIONS: PLWHIV and PLWHCV are less likely than otherwise similar patients to undergo EGS procedures. Further efforts are warranted to ensure equitable access to EGS care for PLWHIV and PLWHCV.

Associations of the COVID-19 pandemic with quality of life: A cross-sectional study of older-age people with and without HIV in rural Uganda.

Background: COVID-19-related lockdowns and other public health measures may have differentially affected the quality of life (QOL) of older people with and without human immunodeficiency virus (HIV) in rural Uganda. Methods: The Quality of Life and Aging with HIV in Rural Uganda study enrolled people with and without HIV aged over 49 from October 2020 to October 2021. We collected data on COVID-19-related stressors (behavior changes, concerns, interruptions in health care, income, and food) and the participants' QOL. We used linear regression to estimate the associations between COVID-19-related stressors and QOL, adjusting for demographic characteristics, mental and physical health, and time before vs after the lockdown during the second COVID-19 wave in Uganda. Interaction between HIV and COVID-19-related stressors evaluated effect modification. Results: We analyzed complete data from 562 participants. Mean age was 58 (standard deviation (SD) = 7); 265 (47%) participants were female, 386 (69%) were married, 279 (50%) had HIV, and 400 (71%) were farmers. Those making ≥5 COVID-19-related behavior changes compared to those making ≤2 had worse general QOL (estimated linear regression coefficient (b) = - 4.77; 95% confidence interval (CI) = -6.61, -2.94) and health-related QOL (b = -4.60; 95% CI = -8.69, -0.51). Having access to sufficient food after the start of the COVID-19 pandemic (b = 3.10, 95% CI = 1.54, 4.66) and being interviewed after the start of the second lockdown (b = 2.79, 95% CI = 1.30, 4.28) were associated with better general QOL. Having HIV was associated with better health-related QOL (b = 5.67, 95% CI = 2.91,8.42). HIV was not associated with, nor did it modify the association of COVID-19-related stressors with general QOL. Conclusions: In the context of the COVID-19 pandemic in an HIV-endemic, low-resource setting, there was reduced QOL among older Ugandans making multiple COVID-19 related behavioral changes. Nonetheless, good QOL during the second COVID-19 wave may suggest resilience among older Ugandans.

Cigarette smoking and misperceived norms among adults in rural Uganda: a population-based study.

BACKGROUND: Little is known about perceived norms about cigarette smoking in Uganda or the extent to which perceptions drive personal cigarette smoking behaviour. METHODS: We conducted a cross-sectional study in 2016-2018 that targeted all adults who resided within eight villages in Rwampara District, southwestern Uganda. Personal cigarette smoking frequency was elicited by self-report. We also asked participants what they believed to be the cigarette smoking frequency of most other adult men and women in their villages (i.e., perceived norms). Frequent cigarette smoking was defined as 4+ times/week. We compared perceived norms to cigarette smoking frequency reports aggregated at the village level. We used multivariable Poisson regression to estimate the association between perceived norms and personal cigarette smoking behaviour. RESULTS: Among 1626 participants (91% response rate), 92 of 719 men (13%) and 6 of 907 women (0.7%) reported frequent smoking. However, 1030 (63%) incorrectly believed most men in their villages smoked cigarettes frequently. Additionally, 116 (7%) incorrectly believed that most women in their villages smoked cigarettes frequently. These misperceptions were pervasive across social strata. Men who misperceived frequent cigarette smoking as the norm among other men in their villages were more likely to smoke frequently themselves (adjusted relative risk=1.49; 95% CI, 1.13 to 1.97). CONCLUSIONS: Most adults overestimated cigarette smoking frequency among village peers. Men who incorrectly believed that frequent smoking was the norm were more likely to engage in frequent smoking themselves. Applying a 'social norms approach' intervention by promoting existing healthy norms may prevent smoking initiation or motivate reductions in smoking among men in rural Uganda.

Urbanicity, posttraumatic stress disorder, and effect modification by socioeconomic position: A nested case-control study of the Korean National Health Insurance Database.

BACKGROUND: We aimed to estimate the association between urbanicity and the onset of posttraumatic stress disorder (PTSD) and to investigate heterogeneity therein according to age and socioeconomic position (SEP). METHODS: We analyzed administrative data from the Korean National Health Insurance Database for patients with PTSD from 2004 to 2018 (N = 109,230) and for a 1:4 sample of age-, sex-, and enrollment year-matched controls. Information on eligibility, SEP (proxied by insurance premium), place of residence, diagnosis, and medical claims was obtained. Urbanicity of administrative districts was assessed using data from the Korean Statistical Information Service, 2005-2018. We estimated hazard ratios (HRs) from baseline and time-dependent models. Subgroup analyses and polynomial splines were used to investigate heterogeneity by age and SEP. RESULTS: Urbanicity was associated with an increased risk of PTSD (per 10%p increase, HR = 1.056, 95% CI 1.050-1.061). A positive association was estimated among patients aged 0-29 years (HR = 1.115, CI 1.106-1.124), while negative associations were estimated among patients aged 30-64 years (HR = 0.990, CI 0.987-0.994) and 65 years or older (HR = 0.992, CI 0.979-1.014). The estimated associations with urbanicity were more prominent at the extremes of SEP, but only among younger participants. CONCLUSION: Urban residence was associated with an increased risk of PTSD diagnosis. The estimated association was larger among younger individuals (but not among middle-aged and older individuals). Among younger individuals, the estimated association was larger at both extremes of SEP.

Linkage to HIV Care Following HIV Self-testing Among Men: Systematic Review of Quantitative and Qualitative Studies from Six Countries in Sub-Saharan Africa.

Gender disparities are pervasive throughout the HIV care continuum in sub-Saharan Africa, with men testing, receiving treatment, and achieving viral suppression at lower rates, and experiencing mortality at higher rates, compared with women. HIV self-testing (HIVST) has been shown to be highly acceptable among men in sub-Saharan Africa. However, evidence on linkage to HIV care following a reactive HIVST result is limited. In this systematic review, we aimed to synthesize the quantitative and qualitative literature from sub-Saharan Africa on men's rates of linkage to HIV care after receiving a reactive HIVST result. We systematically searched 14 bibliometric databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram was used to document the screening results. The Mixed Methods Appraisal Tool (MMAT) was used to assess the methodological quality of the included studies. Of 22,446 references screened, 15 articles were eligible for inclusion in this review. Linkage to HIV care following a reactive HIVST result was subject to several barriers: financial constraints due to travelling costs, potential long waiting hours at the clinics, stigma, discrimination, and privacy concerns. Men's rates of seeking confirmatory testing and linking to HIV care following a reactive HIVST result were inconsistent across studies. Combining financial incentives with HIVST was found to increase the likelihood of linking to HIV care following a reactive HIVST result. The variable rates of linkage to HIV care following a reactive HIVST result suggest a need for further research and development into strategies to increase linkage to HIV care.

Lung function and atherosclerosis: a cross-sectional study of multimorbidity in rural Uganda.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of global mortality. In high-income settings, the presence of cardiovascular disease among people with COPD increases mortality and complicates longitudinal disease management. An estimated 26 million people are living with COPD in sub-Saharan Africa, where risk factors for co-occurring pulmonary and cardiovascular disease may differ from high-income settings but remain uncharacterized. As non-communicable diseases have become the leading cause of death in sub-Saharan Africa, defining multimorbidity in this setting is critical to inform the required scale-up of existing healthcare infrastructure. METHODS: We measured lung function and carotid intima media thickness (cIMT) among participants in the UGANDAC Study. Study participants were over 40 years old and equally divided into people living with HIV (PLWH) and an age- and sex-similar, HIV-uninfected control population. We fit multivariable linear regression models to characterize the relationship between lung function (forced expiratory volume in one second, FEV1) and pre-clinical atherosclerosis (cIMT), and evaluated for effect modification by age, sex, smoking history, HIV, and socioeconomic status. RESULTS: Of 265 participants, median age was 52 years, 125 (47%) were women, and 140 (53%) were PLWH. Most participants who met criteria for COPD were PLWH (13/17, 76%). Median cIMT was 0.67 mm (IQR: 0.60 to 0.74), which did not differ by HIV serostatus. In models adjusted for age, sex, socioeconomic status, smoking, and HIV, lower FEV1 was associated with increased cIMT (ß = 0.006 per 200 mL FEV1 decrease; 95% CI 0.002 to 0.011, p = 0.01). There was no evidence that age, sex, HIV serostatus, smoking, or socioeconomic status modified the relationship between FEV1 and cIMT. CONCLUSIONS: Impaired lung function was associated with increased cIMT, a measure of pre-clinical atherosclerosis, among adults with and without HIV in rural Uganda. Future work should explore how co-occurring lung and cardiovascular disease might share risk factors and contribute to health outcomes in sub-Saharan Africa.

A mixed-methods, population-based study of a syndemic in Soweto, South Africa.

A syndemic has been theorized as a cluster of epidemics driven by harmful social and structural conditions wherein the interactions between the constitutive epidemics drive excess morbidity and mortality. We conducted a mixed-methods study to investigate a syndemic in Soweto, South Africa, consisting of a population-based quantitative survey (N = 783) and in-depth, qualitative interviews (N = 88). We used ethnographic methods to design a locally relevant measure of stress. Here we show that multimorbidity and stress interacted with each other to reduce quality of life. The paired qualitative analysis further explored how the quality-of-life impacts of multimorbidity were conditioned by study participants' illness experiences. Together, these findings underscore the importance of recognizing the social and structural drivers of stress and how they affect the experience of chronic illness and well-being.

Analysis of Suicide After Cancer Diagnosis by US County-Level Income and Rural vs Urban Designation, 2000-2016.

Importance: Studies suggest the risk of suicide among people with cancer diagnosis is higher compared with the general population. However, little is known about how suicide risk among people diagnosed with cancer might vary according to area-level income and rurality. Objective: To examine whether the risks and patterns of suicide mortality among people with a cancer diagnosis differ by US county-level median income and rural or urban status. Design, Setting, and Participants: A retrospective, population-based cohort study following up individuals who were diagnosed with cancer between January 1, 2000, and December 31, 2016, was conducted. The Surveillance, Epidemiology, and End Results Program 18 registries (SEER 18) database was used to obtain data on persons diagnosed with a first primary malignant tumor. Comparisons with the general US population were based on mortality data collected by the National Center for Health Statistics. Analyses were conducted from February 22 to October 14, 2020. Exposures: County-level median household income and urban or rural status. Main Outcomes and Measures: Standardized mortality ratios (SMRs) of suicide deaths and annual percentage changes (APCs) of SMRs. Results: The SEER 18 database included 5 362 782 persons with cancer diagnoses living in 635 counties. Most study participants were men (51.2%), White (72.2%), and older than 65 years (49.7%). Among them, 6357 persons died of suicide (SMR, 1.41; 95% CI, 1.38-1.44). People with cancer living in the lowest-income counties had a significantly higher risk (SMR, 1.94; 95% CI, 1.76-2.13) than those in the highest-income counties (SMR, 1.30; 95% CI, 1.26-1.34). Those living in rural counties also had significantly higher SMR than those in urban counties (SMR, 1.81; 95% CI, 1.70-1.92 vs SMR, 1.35; 95% CI, 1.32-1.39). For all county groups, the SMRs were the highest within the first year following cancer diagnosis. However, among people living in the lowest-income counties, the risk remained significantly high even after 10 or more years following cancer diagnosis (SMR, 1.83; 95% CI, 1.31-2.48). The comparative risk of suicide mortality within 1 year following cancer diagnosis significantly decreased over the years but then plateaued in the highest-income (2005-2015: APC, 2.03%; 95% CI, -0.97% to 5.13%), lowest-income (2010-2015: APC, 4.80%; 95% CI, -19.97% to 37.24%), and rural (2004-2015: APC, 1.83; 95% CI, -1.98% to 5.79%) counties. Conclusions and Relevance: This cohort study showed disparities in suicide risks and their patterns among people diagnosed with cancer by county-level income and rural or urban status. The findings suggest that additional research and effort to provide psychological services addressing these disparities among people with cancer may be beneficial.

A syndemic of psychiatric morbidity, substance misuse, violence, and poor physical health among young Scottish men with reduced life expectancy.

BACKGROUND: Scotland has the shortest life expectancy in Western Europe, driven by high rates of cancer, suicides, alcohol-related causes and drug-related poisonings. These disparities cannot be explained solely by socioeconomic deprivation. Our aim was to investigate whether a syndemic in a socioeconomically deprived area of Glasgow might account for premature mortality among men. METHODS: We analysed data from two cross-sectional population surveys: a national sample of 1916 British men and another of 765 men in Glasgow East. The survey included men aged 18-34, and was undertaken in 2011 to study correlates of violence. Questionnaires covered current physical health, psychiatric symptoms, substance misuse, and crime and violence. Syndemic components were identified using confirmatory factor analysis. Associations and synergistic interactions between these variables and health status were estimated using logistic regression. RESULTS: An aggregation of multiple health conditions and health-related behaviours was found in Glasgow East. A syndemic model of joint effects, adducing a four-component latent variable (violence, substance dependence, psychiatric morbidity and a diathesis of biological/behavioural risk) showed synergy between components and explained persistent disparities in poor physical health/chronic health conditions. Effect modification was found between the general syndemic factor and contextual variables at individual and social environmental level according to location. CONCLUSIONS: Syndemic effects from synergistic interactions were confirmed between psychiatric morbidity, substance misuse, violence, and biological/behavioural risk for physical health. A hypothetical model was developed to explain how the syndemic leads to potentially life-threatening risks to young men, both currently and as precursors of physical health conditions which may shorten their lives in the future.

Implementing community-based human papillomavirus self-sampling with SMS text follow-up for cervical cancer screening in rural, southwestern Uganda.

BACKGROUND: Self-collected HPV screening may improve cervical cancer screening coverage in low resource countries, yet data guiding implementation and follow-up of abnormal results are sparse. METHODS: This is a prospective cohort implementation study of HPV self-testing program in Mbarara, Uganda with mobile phones to facilitate result notification and referral for treatment at a regional hospital. The effectiveness of the interventions was analyzed using Proctor's model of implementation. Women were interviewed following screening and at 6 months to assess acceptability and barriers to follow-up. Data were analyzed using descriptive statistics. RESULTS: 159 of 194 (82%) of eligible women underwent HPV self-sampling; of these, 27 (17%) returned positive for high-risk HPV subtypes. We sent SMS messages providing test results and follow-up instructions to all participants. Seventeen (63%) hrHPV-positive participants reported receiving SMS text instructions for follow-up, of whom 6 (35%) presented for follow-up. The most common reasons for not returning were: lack of transportation (n = 11), disbelief of results (n = 5), lack of childcare (n = 4), and lack of symptoms (n = 3). Confidence in test results was higher for self-screening compared to VIA (Likert score 4.8 vs 4.4, P = 0.001). CONCLUSIONS: Despite the use of SMS text-based referrals, only one-third of women presented for clinical follow-up after abnormal HPV testing.

Blood pressure trajectories and the mediated effects of body mass index and HIV-related inflammation in a mixed cohort of people with and without HIV in rural Uganda.

We sought to describe changes in blood pressure and estimate the effect of HIV on blood pressure (BP) over 4 years of observation in a cohort of 155 HIV-infected adults (≥40 years) on antiretroviral therapy (ART) and 154 sex- and age-quartile-matched, population-based, HIV-uninfected controls for four years in rural Uganda, we compared changes in blood pressure (BP) by HIV serostatus and tested whether body mass index and inflammation (high-sensitivity C-reactive protein and interleukin-6) and immune activation (sCD14 and sCD163) mediated the effects of HIV on BP using hierarchical multivariate and two-stage parametric regression models. Overall HIV-uninfected participants had higher mean BP than HIV-infected counterparts (differences in trend P < 0.0001 for diastolic BP and P = 0.164 for systolic BP). After initial declines in BP in both groups between years 1 and 2, BP moderately increased in both groups through year 4, with greater change over time observed in the HIV-uninfected group. Body mass index mediated 72% (95%CI 57, 97) of the association between HIV and systolic BP. We found a minimal mediating effect of sCD14 on the relationship between HIV and SBP (9%, 95% CI 5%, 21%), but found no association between other HIV-related biomarkers. Over four years of observation, HIV-infected people in rural Uganda have lower BP than HIV-uninfected counterparts despite having higher levels of inflammation. BMI, rather than measures of HIV-associated inflammation, explained a majority of the difference in BP observed.

Community beliefs, HIV stigma, and depression among adolescents living with HIV in rural Uganda.

The availability of and increased access to antiretroviral therapy (ART) has significantly reduced the morbidity and mortality associated with HIV. As a result, perinatally infected youth are increasingly able to reach adolescence. There is limited information about the psychosocial challenges facing adolescents living with HIV (ALWH) in rural settings of sub-Saharan Africa. We sought to understand psychosocial challenges facing ALWH in rural Uganda and their effects on mental health and HIV treatment outcomes. We conducted 5 focus group discussions and 40 one-on-one in-depth interviews in Mbarara, Uganda with adolescents (aged 13-17 years) and adult women caregivers. All interviews were audio-recorded, transcribed directly into English, and coded using thematic analysis to identify themes related to psychosocial adversities and mental health. Adversities faced by adolescents included negative community perceptions (perceived aggression, presumed early mortality), HIV stigma (enacted and internalized), vulnerability factors (loss of parents, poverty), and health challenges (depression, ART non-adherence). In the conceptual model that emerged from the findings, negative community perceptions (about perceived aggression or presumed early mortality) predisposed ALWH to experience enactments and internalization of stigma that led to depression and ART non-adherence. The data also identified several protective factors, including counselling, family and religious support, and timely serostatus disclosure. Interventions to correct community misperceptions about HIV can potentially reduce stigma and thereby improve physical and mental health outcomes of ALWH.

College affirmative action bans and smoking and alcohol use among underrepresented minority adolescents in the United States: A difference-in-differences study.

BACKGROUND: College affirmative action programs seek to expand socioeconomic opportunities for underrepresented minorities. Between 1996 and 2013, 9 US states-including California, Texas, and Michigan-banned race-based affirmative action in college admissions. Because economic opportunity is known to motivate health behavior, banning affirmative action policies may have important adverse spillover effects on health risk behaviors. We used a quasi-experimental research design to evaluate the association between college affirmative action bans and health risk behaviors among underrepresented minority (Black, Hispanic, and Native American) adolescents. METHODS AND FINDINGS: We conducted a difference-in-differences analysis using data from the 1991-2015 US national Youth Risk Behavior Survey (YRBS). We compared changes in self-reported cigarette smoking and alcohol use in the 30 days prior to survey among underrepresented minority 11th and 12th graders in states implementing college affirmative action bans (Arizona, California, Florida, Michigan, Nebraska, New Hampshire, Oklahoma, Texas, and Washington) versus outcomes among those residing in states not implementing bans (n = 35 control states). We also assessed whether underrepresented minority adults surveyed in the 1992-2015 Tobacco Use Supplement to the Current Population Survey (TUS-CPS) who were exposed to affirmative action bans during their late high school years continued to smoke cigarettes between the ages of 19 and 30 years. Models adjusted for individual demographic characteristics, state and year fixed effects, and state-specific secular trends. In the YRBS (n = 34,988 to 36,268, depending on the outcome), cigarette smoking in the past 30 days among underrepresented minority 11th-12th graders increased by 3.8 percentage points after exposure to an affirmative action ban (95% CI: 2.0, 5.7; p < 0.001). In addition, there were also apparent increases in past-30-day alcohol use, by 5.9 percentage points (95% CI: 0.3, 12.2; p = 0.041), and past-30-day binge drinking, by 3.5 percentage points (95% CI: -0.1, 7.2, p = 0.058), among underrepresented minority 11th-12th graders, though in both cases adjustment for multiple comparisons resulted in failure to reject the null hypothesis (adjusted p = 0.083 for both outcomes). Underrepresented minority adults in the TUS-CPS (n = 71,575) exposed to bans during their late high school years were also 1.8 percentage points more likely to report current smoking (95% CI: 0.1, 3.6; p = 0.037). Event study analyses revealed a discrete break for all health behaviors timed with policy discussion and implementation. No substantive or statistically significant effects were found for non-Hispanic White adolescents, and the findings were robust to a number of additional specification checks. The limitations of the study include the continued potential for residual confounding from unmeasured time-varying factors and the potential for recall bias due to the self-reported nature of the health risk behavior outcomes. CONCLUSIONS: In this study, we found evidence that some health risk behaviors increased among underrepresented minority adolescents after exposure to state-level college affirmative action bans. These findings suggest that social policies that shift socioeconomic opportunities could have meaningful population health consequences.

Association of Gut Intestinal Integrity and Inflammation with Insulin Resistance in Adults Living with HIV in Uganda.

We conducted a cross-sectional study of 148 HIV+ on HIV antiretroviral therapy and 149 HIV- adults in Mbarara, Uganda, to estimate the association between HIV infection and homeostasis model assessment of insulin resistance (HOMA-IR) using multivariable regression analysis. In addition, we evaluated whether intestinal fatty acid-binding protein (I-FABP), monocyte activation markers soluble (s)CD14 and sCD163, and proinflammatory cytokine interleukin 6 (IL-6) mediated this association. HOMA-IR was greater among HIV+ than HIV- adults [median (interquartile range): 1.3 (0.7-2.5) vs. 0.9 (0.5-2.4); p = 0.008]. In models adjusted for sociodemographic variables, diet, hypertension, and smoking history, HIV infection was associated with 37% [95% confidence intervals (95% CIs): 5-77] greater HOMA-IR compared with HIV- participants. The magnitude of association was greater when I-FABP was included as a covariate although the additive effect was modest (40% CI: 8-82). By contrast adding sCD14 to the model was associated with greater HOMA-IR (59%; 95% CI: 21-109) among HIV+ participants compared with HIV- participants. Among HIV+ participants, greater CD4 nadir was non-significantly associated with greater HOMA-IR (22%; 95% CI: -2 to 52). Each 5-unit increase in body mass index (BMI; 49% greater HOMA-IR; 95% CI: 18-87) and female sex (71%; 95% CI: 17-150) remained associated in adjusted models. In this study of mainly normal-weight Ugandan adults, HIV infection, female sex, and greater BMI were all associated with greater insulin resistance (IR). This association was strengthened modestly after adjustment for sCD14, suggesting possible distinct immune pathways to IR that are independent of HIV or related to inflammatory changes occurring on HIV treatment.

Female sex and cardiovascular disease risk in rural Uganda: a cross-sectional, population-based study.

BACKGROUND: Sex-based differences in cardiovascular disease (CVD) burden are widely acknowledged, with male sex considered a risk factor in high-income settings. However, these relationships have not been examined in sub-Saharan Africa (SSA). We aimed to apply the American Heart Association (AHA) ideal cardiovascular health (CVH) tool modified by the addition of C-reactive protein (CRP) to examine potential sex-based differences in the prevalence of CVD risk in rural Uganda. METHODS: In a cross-sectional study nested within a population-wide census, 857 community-living adults completed physical and laboratory-based assessments to calculate individual ideal CVH metrics including an eight category for CRP levels. We summarized sex-specific ideal CVH indices, fitting ordinal logistic regression models to identify correlates of improving CVH. As secondary outcomes, we assessed subscales of ideal CVH behaviours and factors. Models included inverse probability of sampling weights to determine population-level estimates. RESULTS: The weighted-population mean age was 39.2 (1.2) years with 52.0 (3.7) % females. Women had ideal scores in smoking (80.4% vs. 68.0%; p < 0.001) and dietary intake (26.7% vs. 16.8%; p = 0.037) versus men, but the opposite in body mass index (47.3% vs. 84.4%; p < 0.001), glycated hemoglobin (87.4% vs. 95.2%; p = 0.001), total cholesterol (80.2% vs. 85.0%; p = 0.039) and CRP (30.8% vs. 49.7%; p = 0.009). Overall, significantly more men than women were classified as having optimal cardiovascular health (6-8 metrics attaining ideal level) (39.7% vs. 29.0%; p = 0.025). In adjusted models, female sex was correlated with lower CVH health factors sub-scales but higher ideal CVH behaviors. CONCLUSIONS: Contrary to findings in much of the world, female sex in rural SSA is associated with worse ideal CVH profiles, despite women having better indices for ideal CVH behaviors. Future work should assess the potential role of socio-behavioural sex-specific risk factors for ideal CVH in SSA, and better define the downstream consequences of these differences.

ART adherence and viral suppression are high among most non-pregnant individuals with early-stage, asymptomatic HIV infection: an observational study from Uganda and South Africa.

INTRODUCTION: The success of universal antiretroviral therapy (ART) access and aspirations for an AIDS-free generation depend on high adherence in individuals initiating ART during early-stage HIV infection; however, adherence may be difficult in the absence of illness and associated support. METHODS: From March 2015 to October 2017, we prospectively observed three groups initiating ART in routine care in Uganda and South Africa: men and non-pregnant women with early-stage HIV infection (CD4 > 350 cells/µL), pregnant women with early-stage HIV infection and men and non-pregnant women with late-stage HIV infection (CD4 < 200 cells/µL). Socio-behavioural questionnaires were administered and viral loads were performed at 0, 6 and 12 months. Adherence was monitored electronically. RESULTS: Adherence data were available for 869 participants: 322 (37%) early/non-pregnant, 199 (23%) early/pregnant and 348 (40%) late/non-pregnant participants. In Uganda, median adherence was 89% (interquartile range 74 to 96) and viral suppression was 90% at 12 months; neither differed among groups (p > 0.72). In South Africa, median adherence was higher in early/non-pregnant versus early/pregnant or late/non-pregnant participants (76%, 37%, 52%; p < 0.001), with similar trends in viral suppression (86%, 51%, 79%; p < 0.001). Among early/non-pregnant individuals in Uganda, adherence was higher with increasing age and lower with structural barriers; whereas in South Africa, adherence was higher with regular income, higher perceived stigma and use of other medications, but lower with maladaptive coping and cigarette smoking. DISCUSSION: ART adherence among non-pregnant individuals with early-stage infection is as high or higher than with late-stage initiation, supporting universal access to ART. Challenges remain for some pregnant women and individuals with late-stage infection in South Africa and highlight the need for differentiated care delivery.

HIV knowledge trends during an era of rapid antiretroviral therapy scale-up: an analysis of 33 sub-Saharan African countries.

INTRODUCTION: Population-level improvements in knowledge about HIV may reduce the stigma attached to HIV and ensure maximal uptake of HIV prevention initiatives. The extent to which levels of HIV knowledge in the general population of sub-Saharan Africa have changed in the current era of antiretroviral therapy (ART) scale-up remains unknown. METHODS: Data on HIV knowledge in the general population were drawn from the 2003 to 2015 Demographic and Health Surveys (DHS) and AIDS Indicator Surveys (AIS) of 33 countries in sub-Saharan Africa. The DHS/AIS contain five questions on HIV prevention and transmission that have been used by the Joint United Nations Programme on HIV/AIDS (UNAIDS) as a core indicator of HIV knowledge. We created a composite HIV knowledge variable equal to the number of correct responses to these five questions; a participant was considered to have comprehensive knowledge of HIV (yes/no) if he/she answered all five questions correctly. We fitted negative binomial regression models with cluster-correlated robust standard errors and country fixed effects, adjusted for socio-demographic variables, specifying HIV knowledge as the dependent variable and year as the explanatory variable. As an alternative parameterization, we also fitted a multivariable linear probability model with cluster-correlated robust standard errors and country fixed effects specifying comprehensive knowledge of HIV as the dependent variable. RESULTS: A total of 791,186 women and 395,891 men participating in 75 DHS/AIS were included in the analyses. The mean HIV knowledge score was 3.7 among women and 3.9 among men (p < 0.001). Only 35% of women and 41% of men (p < 0.001) had a comprehensive knowledge of HIV. We estimated a modest but statistically significant positive association between year of DHS/AIS and HIV knowledge (adjusted b = 0.005; 95% confidence interval (CI), 0.001 to 0.009). Similarly, we estimated a statistically significant positive association between year of DHS/AIS and comprehensive knowledge of HIV (adjusted b = 0.011; 95% CI, 0.005 to 0.017), suggesting an approximately 1% relative increase per year in the percentage of the general population who possess a comprehensive knowledge of HIV. CONCLUSIONS: There have been minimal improvements over time in HIV knowledge across sub-Saharan Africa.

CYP2B6 Genetic Polymorphisms, Depression, and Viral Suppression in Adults Living with HIV Initiating Efavirenz-Containing Antiretroviral Therapy Regimens in Uganda: Pooled Analysis of Two Prospective Studies.

Single-nucleotide polymorphisms (SNPs) in CYP2B6 have been shown to predict variation in plasma efavirenz concentrations, but associations between these SNPs and efavirenz-mediated depression and viral suppression are less well described. We evaluated three SNPs in CYP2B6 (rs3745274, rs28399499, and rs4803419) in Ugandan persons living with HIV. To define exposure, we used previously published pharmacokinetic modeling data to categorize participants as normal, intermediate, and poor efavirenz metabolizers. Our outcomes were probable depression in the first 2 years after antiretroviral therapy (ART) initiation (mean score of >1.75 on the Hopkins Symptom Depression Checklist) and viral suppression 6 months after ART initiation. We fit generalized estimating equation and modified Poisson regression models adjusted for demographic, clinical, and psychosocial characteristics with or without individuals with depression at the time of ART initiation. Among 242 participants, there were no differences in the pre-ART depression or viral load by efavirenz metabolism strata (p > .05). Participants were classified as normal (32%), intermediate (50%), and poor (18%) metabolizers. Seven percent (56/242) of follow-up visits met criteria for depression. Eighty-five percent (167/202) of participants who completed a 6-month visit achieved viral suppression. CYP2B6 metabolizer strata did not have a statistically significant association with either depression [adjusted risk ratio (aRR) comparing intermediate or poor vs. normal, 1.46; 95% confidence interval (CI), 0.72-2.95] or 6-month viral suppression (aRR, 1.01; 95% CI, 0.88-1.15). However, in analyses restricted to participants without pre-ART depression, poorer CYP2B6 metabolism was associated with increased odds of depression (adjusted odds ratio, 4.11; 95% CI, 1.04-16.20). Efavirenz-metabolizing allele patterns are strongly associated with risk of incident depression. Future work should elucidate further region-specific gene-environment interactions and whether alternate polymorphisms may be associated with efavirenz metabolism.

Smoking cessation after engagement in HIV care in rural Uganda.

People living with HIV (PLWH) are more likely to smoke compared to HIV-uninfected counterparts, but little is known about smoking behaviors in sub-Saharan Africa. To address this gap in knowledge, we characterized smoking cessation patterns among people living with HIV (PLWH) compared to HIV-uninfected individuals in rural Uganda. PLWH were at least 40 years of age and on antiretroviral therapy for at least three years, and HIV-uninfected individuals were recruited from the clinical catchment area. Our primary outcome of interest was smoking cessation, which was assessed using an adapted WHO STEPS smoking questionnaire. We fit Cox proportional hazards models to compare time to smoking cessation between PLWH pre-care, PLWH in care, and HIV-uninfected individuals. We found that, compared to HIV-uninfected individuals, PLWH in care were less likely to have ever smoked (40% vs. 49%, p = 0.04). The combined sample of 267 ever-smokers had a median age of 56 (IQR 49-68), 56% (n = 150) were male, and 26% (n = 70) were current smokers. In time-to-event analyses, HIV-uninfected individuals and PLWH prior to clinic enrollment ceased smoking at similar rates (HR 0.8, 95% CI 0.5-1.2). However, after enrolling in HIV care, PLWH had a hazard of smoking cessation over twice that of HIV-uninfected individuals and three times that of PLWH prior to enrollment (HR 2.4, 95% CI 1.3-4.6, p = 0.005 and HR 3.0, 95% CI 1.6-5.5, p = 0.001, respectively). In summary, we observed high rates of smoking cessation among PLWH after engagement in HIV care in rural Uganda. While we hypothesize that greater access to primary care services and health counseling might contribute, future studies should better investigate the mechanism of this association.