Chronic Conditions and Multimorbidity Among Middle-Aged and Elderly Peri-Urban Dwellers in Dar es Salaam, Tanzania

Objectives: Chronic conditions and multimorbidity affect care needs and prevention opportunities. Methods: We studied 2,246 men and women aged ≥40 years within the Dar es Salaam Urban Cohort Study from June 2017 to July 2018. Seventeen chronic conditions were assessed based on self-report, body and blood pressure measurement, blood tests, and screening instruments. Results: Hypertension (51.3%), anemia (34.1%), obesity (32.2%), diabetes (31.6%), depressive symptoms (31.5%), low grip strength (21.2%), and ischemic heart disease (11.9%) were widespread. Multimorbidity was common (73.7%). Women had higher odds of obesity, ischemic heart disease, and high cholesterol (adjusted OR: 2.08–4.16) and lower odds of underweight, low grip strength, alcohol problems, and smoking (adjusted OR: 0.04–0.45). Ten years of age were associated with higher odds of low grip strength, cognitive problems, hypertension, kidney disease, chronic cough, diabetes, high cholesterol, ischemic heart disease, and multimorbidity (adjusted OR: 1.21–1.81) and lower odds of HIV infection (adjusted OR: 0.51). Conclusion: We found a higher prevalence of multimorbidity than previously estimated for middle-aged and elderly people in sub-Saharan Africa. The chronic conditions underlying multimorbidity differed by sex

Depressive symptoms and their association with age, chronic conditions and health status among middle-aged and elderly people in peri-urban Tanzania

Abstract Background Depression is a global mental health challenge. We assessed the prevalence of depressive symptoms and their association with age, chronic conditions, and health status among middle-aged and elderly people in peri-urban Dar es Salaam, Tanzania. Methods Depressive symptoms were measured in 2,220 adults aged over 40 years from two wards of Dar es Salaam using the ten-item version of the Center of Epidemiologic Studies Depression Scale (CES-D-10) and a cut-off score of 10 or higher. The associations of depressive symptoms with age, 13 common chronic conditions, multimorbidity, self-rated health and any limitation in six activities of daily living were examined in univariable and multivariable logistic regressions. Results The estimated prevalence of depressive symptoms was 30.7% (95% CI 28.5–32.9). In univariable regressions, belonging to age groups 45–49 years (OR 1.35 [95% CI 1.04–1.75]) and over 70 years (OR 2.35 [95% CI 1.66–3.33]), chronic conditions, including ischemic heart disease (OR 3.43 [95% CI 2.64–4.46]), tuberculosis (OR 2.42 [95% CI 1.64–3.57]), signs of cognitive problems (OR 1.90 [95% CI 1.35–2.67]), stroke (OR 1.56 [95% CI 1.05–2.32]) and anemia (OR 1.32 [95% CI 1.01–1.71]) and limitations in activities of daily living (OR 1.35 [95% CI 1.07–1.70]) increased the odds of depressive symptoms. Reporting good or very good health was associated with lower odds of depressive symptoms (OR 0.48 [95% CI 0.35–0.66]). Ischemic heart disease and tuberculosis remained independent predictors of depressive symptoms in multivariable regressions. Conclusion Depressive symptoms affected almost one in three people aged over 40 years. Their prevalence differed across age groups and was moderated by chronic conditions, health status and socioeconomic factors

Marginal structural models to assess delays in second-line HIV treatment initiation in South Africa

BACKGROUND South African HIV treatment guidelines call for patients who fail first-line antiretroviral therapy (ART) to be switched to second-line ART, yet logistical issues, clinician decisions and patient preferences make delay in switching to second-line likely. We explore the impact of delaying second-line ART after first-line treatment failure on rates of death and virologic failure. METHODS We include patients with documented virologic failure on first-line ART from an observational cohort of 9 South African clinics. We explored predictors of delayed second-line switch and used marginal structural models to analyze rates of death following first-line failure by categorical time to switch to second-line. Cox proportional hazards models were used to examine virologic failure on second-line ART among patients who switched to second- line. RESULTS 5895 patients failed first-line ART, and 63% switched to second-line. Among patients who switched, median time to switch was 3.4 months (IQR: 1.1–8.7 months). Longer time to switch was associated with higher CD4 counts, lower viral loads and more missed visits prior to first-line failure. Worse outcomes were associated with delay in second-line switch among patients with a peak CD4 count on first-line treatment 100 cells/mm3. Among these patients, marginal structural models showed increased risk of death (adjusted HR for switch in 6–12 months vs. 0–1.5 months = 1.47 (95% CI: 0.94–2.29), and Cox models showed increased rates of second-line virologic failure despite the presence of survivor bias (adjusted HR for switch in 3–6 months vs. 0–1.5 months = 2.13 (95% CI: 1.01–4.47)). CONCLUSIONS Even small delays in switch to second-line ART were associated with increased death and second-line failure among patients with low CD4 counts on first-line. There is opportunity for healthcare providers to switch patients to second-line more quickly.S1 Fig. Illustration of allocation of person time in marginal structural models. Hypothetical person time contributed to each of the 6 exposure groups in marginal structural models.S1 Table. Alternative stratifications for adjusted marginal structural models for hazard ratios of death after first-line failure.S2 Table. Adjusted marginal structural model hazard ratios for death after first-line failure, limiting to patients with 2 weeks to <8 months between failing viral loads on first-line (n = 4908).S3 Table. Adjusted Cox proportional hazards ratios for alternative virologic outcomes on second-line ART, stratified by peak CD4 count prior to first-line failure.S4 Table. Adjusted marginal structural models for hazard ratios of death after first-line failure (a) and adjusted Cox proportional hazards ratios for confirmed failure on second-line ART (b), with weighting by inverse probability of censoring after second-line switch to account for loss to follow-up.JKR, KS, MM, LL and MPF were funded for this work by United States Agency for International Development (USAID) through the following agreement: 674-A-12-00029. Additional support to KS was provided by the National Institutes of Health (NIH) (T32AI102623).http://www.plosone.orgam2016Medical Microbiolog

Sexual Behaviors and HIV Status: A Population-Based Study Among Older Adults in Rural South Africa

Objective: To identify the unmet needs for HIV prevention among older adults in rural South Africa. Methods: We analyzed data from a population-based sample of 5059 men and women aged 40 years and older from the study Health and Aging in Africa: Longitudinal Studies of INDEPTH Communities (HAALSI), which was carried out in the Agincourt health and sociodemographic surveillance system in the Mpumalanga province of South Africa. We estimated the prevalence of HIV (laboratory-confirmed and self-reported) and key sexual behaviors by age and sex. We compared sexual behavior profiles across HIV status categories with and without age–sex standardization. Results: HIV prevalence was very high among HAALSI participants (23%, 95% confidence interval [CI]: 21 to 24), with no sex differences. Recent sexual activity was common (56%, 95% CI: 55 to 58) across all HIV status categories. Condom use was low among HIV-negative adults (15%, 95% CI: 14 to 17), higher among HIV-positive adults who were unaware of their HIV status (27%, 95% CI: 22 to 33), and dramatically higher among HIV-positive adults who were aware of their status (75%, 95% CI: 70 to 80). Casual sex and multiple partnerships were reported at moderate levels, with slightly higher estimates among HIV-positive compared to HIV-negative adults. Differences by HIV status remained after age–sex standardization. Conclusions: Older HIV-positive adults in an HIV hyperendemic community of rural South Africa report sexual behaviors consistent with high HIV transmission risk. Older HIV-negative adults report sexual behaviors consistent with high HIV acquisition risk. Prevention initiatives tailored to the particular prevention needs of older adults are urgently needed to reduce HIV risk in this and similar communities in sub-Saharan Africa.The HAALSI study was funded by the NIA of the NIH (P01 AG041710). HAALSI is nested within the Agincourt Health and Socio-Demographic Surveillance System, with funding from Wellcome Trust (058893/Z/99/A; 069683/Z/02/Z; 085477/Z/08/Z; 085477/B/08/Z), University of the Witwatersrand, and Medical Research Council, South Africa. T.W.B. received funding from the Wellcome Trust and NICHD of NIH (R01-HD084233) and NIAID of NIH (R01-AI124389 and R01-AI112339)

Performance of self-reported HIV status in determining true HIV status among older adults in rural South Africa: a validation study

Introduction: In South Africa, older adults make up a growing proportion of people living with HIV. HIV programmes are likely to reach older South Africans in home-based interventions where testing is not always feasible. We evaluate the accuracy of self-reported HIV status, which may provide useful information for targeting interventions or offer an alternative to biomarker testing. Methods: Data were taken from the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) baseline survey, which was conducted in rural Mpumalanga province, South Africa. A total of 5059 participants aged ≥40 years were interviewed from 2014 to 2015. Self-reported HIV status and dried bloodspots for HIV biomarker testing were obtained during at-home interviews. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for self-reported status compared to “gold standard” biomarker results. Log-binomial regression explored associations between demographic characteristics, antiretroviral therapy (ART) status and sensitivity of self-report. Results: Most participants (93%) consented to biomarker testing. Of those with biomarker results, 50.9% reported knowing their HIV status and accurately reported it. PPV of self-report was 94.1% (95% confidence interval (CI): 92.0–96.0), NPV was 87.2% (95% CI: 86.2–88.2), sensitivity was 51.2% (95% CI: 48.2–54.3) and specificity was 99.0% (95% CI: 98.7–99.4). Participants on ART were more likely to report their HIV-positive status, and participants reporting false-negatives were more likely to have older HIV tests. Conclusions: The majority of participants were willing to share their HIV status. False-negative reports were largely explained by lack of testing, suggesting HIV stigma is retreating in this setting, and that expansion of HIV testing and retesting is still needed in this population. In HIV interventions where testing is not possible, self-reported status should be considered as a routine first step to establish HIV status.This study was funded by the National Institute on Aging (NIA) of the National Institutes of Health (NIH) [P01-AG041710] and is nested within the MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt) and funded by Wellcome Trust [058893/Z/99/A; 069683/Z/02/Z; 085477/Z/08/Z; 085477/B/08/Z] with important contributions from the University of the Witwatersrand and the South African Medical Research Council. Till Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. He is also supported by the Wellcome Trust, the European Commission, the Clinton Health Access Initiative and NICHD of NIH [R01-HD084233], NIAID of NIH [R01-AI124389 and R01-AI112339] and FIC of NIH [D43-TW009775]

Sexual Behaviors and HIV Status: A Population-Based Study Among Older Adults in Rural South Africa

Objective: To identify the unmet needs for HIV prevention among older adults in rural South Africa. Methods: We analyzed data from a population-based sample of 5059 men and women aged 40 years and older from the study Health and Aging in Africa: Longitudinal Studies of INDEPTH Communities (HAALSI), which was carried out in the Agincourt health and sociodemographic surveillance system in the Mpumalanga province of South Africa. We estimated the prevalence of HIV (laboratory-confirmed and self-reported) and key sexual behaviors by age and sex. We compared sexual behavior profiles across HIV status categories with and without age–sex standardization. Results: HIV prevalence was very high among HAALSI participants (23%, 95% confidence interval [CI]: 21 to 24), with no sex differences. Recent sexual activity was common (56%, 95% CI: 55 to 58) across all HIV status categories. Condom use was low among HIV-negative adults (15%, 95% CI: 14 to 17), higher among HIV-positive adults who were unaware of their HIV status (27%, 95% CI: 22 to 33), and dramatically higher among HIV-positive adults who were aware of their status (75%, 95% CI: 70 to 80). Casual sex and multiple partnerships were reported at moderate levels, with slightly higher estimates among HIV-positive compared to HIV-negative adults. Differences by HIV status remained after age–sex standardization. Conclusions: Older HIV-positive adults in an HIV hyperendemic community of rural South Africa report sexual behaviors consistent with high HIV transmission risk. Older HIV-negative adults report sexual behaviors consistent with high HIV acquisition risk. Prevention initiatives tailored to the particular prevention needs of older adults are urgently needed to reduce HIV risk in this and similar communities in sub-Saharan Africa

Assessing the association between changing NRTIs when initiating second-line ART and treatment outcomes.

BACKGROUND After first-line antiretroviral therapy (ART) failure, the importance of change in nucleoside reverse transcriptase inhibitor (NRTI) in second-line is uncertain due to the high potency of protease inhibitors used in second-line. SETTING We used clinical data from 6,290 adult patients in South Africa and Zambia from the International Epidemiologic Databases to Evaluate AIDS-Southern Africa cohort. METHODS We included patients who initiated on standard first-line ART and had evidence of first-line failure. We used propensity score-adjusted Cox proportional hazards models to evaluate the impact of change in NRTI on second-line failure compared to remaining on the same NRTI in second-line. In South Africa, where viral load monitoring was available, treatment failure was defined as two consecutive viral loads >1,000 copies/mL. In Zambia, it was defined as two consecutive CD4 counts <100 cells/mm. RESULTS Among patients in South Africa initiated on zidovudine, the adjusted hazard ratio for second-line virologic failure was 0.25 (95% CI: 0.11, 0.57) for those switching to tenofovir vs. remaining on zidovudine. Among patients in South Africa initiated on tenofovir, switching to zidovudine in second-line was associated with reduced second-line failure (adjusted hazard ratio = 0.35 [95% CI: 0.13, 0.96]). In Zambia where viral load monitoring was not available, results were less conclusive. CONCLUSION Changing NRTI in second-line was associated with better clinical outcomes in South Africa. Additional clinical trial research regarding second-line NRTI choices for patients initiated on tenofovir or with contraindications to specific NRTIs is needed

Molecular basis of targeted therapy in T/NKcell lymphoma/leukemia: A comprehensive genomic and immunohistochemical analysis of a panel of 33 cell lines

T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways. The study identified TP53, NOTCH1 and DNMT3A as the most frequently mutated genes. We also found common alterations in JAK/STAT and epigenetic pathways. Immunohistochemical analysis showed nuclear accumulation of MYC (in 85% of the cases), NFKB (62%), p-STAT (44%) and p-MAPK (30%). This panel of cell lines captures the complexity of T/NK-cell lymphoproliferative processes samples, with the partial exception of AITL cases. Integrated mutational and immunohistochemical analysis shows that mutational changes cannot fully explain the activation of key survival pathways and the resulting phenotypes. The combined integration of mutational/expression changes forms a useful tool with which new compounds may be assayed

Performance of self-reported HIV status in determining true HIV status among older adults in rural South Africa: a validation study

Abstract Introduction:: In South Africa, older adults make up a growing proportion of people living with HIV. HIV programmes are likely to reach older South Africans in home-based interventions where testing is not always feasible. We evaluate the accuracy of self-reported HIV status, which may provide useful information for targeting interventions or offer an alternative to biomarker testing. Methods:: Data were taken from the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) baseline survey, which was conducted in rural Mpumalanga province, South Africa. A total of 5059 participants aged ≥40 years were interviewed from 2014 to 2015. Self-reported HIV status and dried bloodspots for HIV biomarker testing were obtained during at-home interviews. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for self-reported status compared to “gold standard” biomarker results. Log-binomial regression explored associations between demographic characteristics, antiretroviral therapy (ART) status and sensitivity of self-report. Results:: Most participants (93%) consented to biomarker testing. Of those with biomarker results, 50.9% reported knowing their HIV status and accurately reported it. PPV of self-report was 94.1% (95% confidence interval (CI): 92.0–96.0), NPV was 87.2% (95% CI: 86.2–88.2), sensitivity was 51.2% (95% CI: 48.2–54.3) and specificity was 99.0% (95% CI: 98.7–99.4). Participants on ART were more likely to report their HIV-positive status, and participants reporting false-negatives were more likely to have older HIV tests. Conclusions:: The majority of participants were willing to share their HIV status. False-negative reports were largely explained by lack of testing, suggesting HIV stigma is retreating in this setting, and that expansion of HIV testing and retesting is still needed in this population. In HIV interventions where testing is not possible, self-reported status should be considered as a routine first step to establish HIV status

Are circumcised men safer sex partners? : Findings from the HAALSI cohort in rural South Africa

Introduction: The real-world association between male circumcision and HIV status has important implications for policy and intervention practice. For instance, women may assume that circumcised men are safer sex partners than non-circumcised men and adjust sexual partnering and behavior according to these beliefs. Voluntary medical male circumcision (VMMC) is highly efficacious in preventing HIV acquisition in men and this biological efficacy should lead to a negative association between circumcision and HIV. However, behavioral factors such as differential selection into circumcision based on current HIV status or factors associated with future HIV status could reverse the association. Here, we examine how HIV prevalence differs by circumcision status in older adult men in a rural South African community, a non-experimental setting in a time of expanding VMMC access. Methods: We analyzed data collected from a population-based sample of 2345 men aged 40 years and older in a rural community served by the Agincourt Health and socio-Demographic Surveillance System site in Mpumalanga province, South Africa. We describe circumcision prevalence and estimate the association between circumcision and laboratory-confirmed HIV status with log-binomial regression models. Results: One quarter of older men reported circumcision, with slightly more initiation-based circumcisions (56%) than hospital-based circumcisions (44%). Overall, the evidence did not suggest differences in HIV prevalence between circumcised and uncircumcised men; however, those who reported hospital-based circumcision were more likely to test HIV-positive [PR (95% CI): 1.28 (1.03, 1.59)] while those who reported initiation-based circumcision were less likely to test HIV-positive [PR (95% CI): 0.68 (0.51, 0.90)]. Effects were attenuated, but not reversed after adjustment for key covariates. Conclusions: Medically circumcised older men in a rural South African community had higher HIV prevalence than uncircumcised men, suggesting that the effect of selection into circumcision may be stronger than the biological efficacy of circumcision in preventing HIV acquisition. The impression given from circumcision policy and dissemination of prior trial findings that those who are circumcised are safer sex partners may be incorrect in this age group and needs to be countered by interventions, such as educational campaigns