Cumulative exposure to depressive symptoms and all-cause mortality among adults with HIV in Kenya, Nigeria, Tanzania, and Uganda.

OBJECTIVE: We estimated the effects of cumulative exposure to depressive symptoms on risk of all-cause mortality among people with HIV (PWH) in four African countries. DESIGN: An analysis of prospective cohort data. METHODS: The African Cohort Study (AFRICOS) is a prospective cohort of people receiving care at twelve clinics in Kenya, Nigeria, Tanzania, and Uganda. Every 6 months from January 2013 to May 2020, participants underwent laboratory monitoring, structured surveys, and assessment of depressive symptom severity using the Center for Epidemiologic Studies Depression Scale (CES-D). All-cause mortality was the outcome of interest. The predictor of interest was a time-updated measure of the percentage of days lived with depression (PDD). Marginal structural Cox proportional hazards regression models were used, adjusting for potential confounders including time-varying alcohol use, drug use, and viral load. RESULTS: Among 2520 enrolled participants, 1479 (59%) were women and the median age was 38 (interquartile range [IQR]: 32-46). At enrollment, 1438 (57%) were virally suppressed (<200 copies/ml) and 457 (18%) had CES-D at least 16, indicating possible depression. Across 9093 observed person-years, the median PDD was 0.7% (IQR: 0-5.9%) with 0.8 deaths per 100 person-years. Leading causes of death included cancer (18% of deaths) and accidents (14%). Models suggested that each 25% absolute increase in PDD was associated with a 69% increase in the risk of all-cause mortality (hazard ratio: 1.69; 95% confidence interval: 1.18-2.43). CONCLUSION: Cumulative exposure to depressive symptoms was substantially associated with the risk of mortality in this cohort of PWH in Africa.

Frequency and Predictors of HIV-Related Cognitive Impairment in East Africa: The Africa Cohort Study (AFRICOS).

BACKGROUND: Medication adherence is a critical issue in achieving viral suppression targets, particularly in resource-limited countries. As HIV-related cognitive impairment (CI) impacts adherence, we examined frequency and predictors of CI in the African Cohort Study. SETTING: Cross-sectional examination of enrollment data from President's Emergency Plan for AIDS Relief supported clinic sites. METHODS: In a 30-minute cognitive assessment, CI was defined as -1SD on 2 tests or -2SD on one, as compared with 429 controls. We performed univariable and multivariable logistic and linear models examining clinical and demographic factors associated with CI and global neuropsychological performance (NP-6). RESULTS: Two thousand four hundred seventy-two HIV+ participants from Kenya (n = 1503), Tanzania (n = 469), and Uganda (n = 500). The mean (SD) age was 39.7 (10.7) years, and 1452 (59%) were women. The majority reported completing or partially completing primary school (n = 1584, 64%). Mean (SD) current and nadir CD4 count were 463 (249) and 204 (221) cells/mm, respectively; 1689 (68%) were on combination antiretroviral therapy. Nine hundred thirty-nine (38%) HIV+ versus 113 (26%) HIV- individuals showed CI: (P < 0.001). We found significant effects of literacy [odds ratio (OR): 0.3; 95% CI: 0.2 to 0.4; P < 0.001] and World Health Organization stage 4 (OR: 1.5; 95% CI: 1.0 to 2.q; P = 0.046) on CI. Tanzanians (OR: 3.2; 95% CI: 2.4 to 4.3; P < 0.001) and Kenyans (OR: 2.0; 95% CI: 1.6 to 2.6; P < 0.001) had higher risk of CI compared with Ugandans. Results were relatively unchanged in predictive models of NP-6, with the only difference being an additional significant effect of current CD4 cell count (coeff: 0.0; 95% CI: 0.0 to 0.0; P = 0.005). CONCLUSIONS: Literacy, country, World Health Organization stage, and current CD4 cell count were associated with increased risk of cognitive dysfunction. Our findings help optimize care practices in Africa, illustrating the importance of strategies for early and effective viral-immunological control.

Noninfectious Comorbidity in the African Cohort Study.

BACKGROUND: Noninfectious comorbid diseases (NCDs) contribute to morbidity and mortality in human immunodeficiency virus (HIV)-infected populations in resource-rich countries. With antiretroviral therapy (ART) scale-up in Africa, understanding burden NCD informs public health strategy. METHODS: At enrollment, participants at 11 HIV clinics in Kenya, Uganda, Tanzania, and Nigeria underwent medical history, physical, laboratory, and neuropsychological assessments to identify elevated blood pressure, hypercholesterolemia, dysglycemia, renal insufficiency, and cognitive impairment. Poisson regression models estimated adjusted relative risks (ARRs) and 95% confidence intervals (CIs) for the number of NCDs associated with factors of interest. Logistic regression was used to evaluate each NCD separately among HIV-infected participants. RESULTS: Among 2720 participants with complete NCD data, 2159 (79.4%) were HIV-infected. Of those, 1426 (66.0%) were taking ART and 813 (37.7%) had at least 1 NCD. HIV infection was associated with more NCDs, especially with ART (ARR, 1.42; 95% CI, 1.22-1.66). In addition to age, body mass index, and program site, ART usage was associated with more NCDs (ARR, 1.50; 95% CI, 1.27-1.78 for virologically suppressed and ARR, 1.38; 95% CI, 1.13-1.68 for viremic) among HIV-infected participants. In participants taking ART, CD4 nadir below 200 cells/mm3 was associated with more NCDs (ARR, 1.43; 95% CI, 1.06-1.93). ART use was independently associated with hypercholesterolemia and dysglycemia. Program site was significantly associated with all comorbidities except renal insufficiency. CONCLUSIONS: HIV infection was a risk for NCDs, which were common in HIV-infected participants, geographically variable, and largely consistent with metabolic complications of first-line ART.

Limitations of the International HIV Dementia Scale in the current era.

OBJECTIVE: The International HIV Dementia Scale (IHDS) was developed as a tool to detect HIV-dementia in both industrialized and resource-limited settings. Studies employing the IHDS have produced mixed results, with recent data suggesting unusually high rates of dementia among Ugandans. This study aimed to define the performance characteristics of the IHDS in three African countries. DESIGN: Cross-sectional study. METHODS: We recruited 2208 HIV-infected and 429 HIV-uninfected individuals from East Africa (Kenya n = 1384; Tanzania n = 368; Uganda n = 456) who underwent testing with the IHDS and a 30-min neuropsychological testing battery. Cognitive impairment was defined as -1SD on two of six tests or -2SD on one test compared with demographically matched controls stratified by age and education. We examined predictive capacity of the IHDS to detect cognitive impairment using receiver-operator characteristic (ROC) curve analysis. RESULTS: The mean (SD) ages of the HIV-infected and HIV-uninfected groups were 39.7 (10.7) and 37.4 (10.4), respectively. Among HIV-infected individuals, 1508 (68%) were on combination antiretroviral therapy (cART), 1298 (61%) had plasma viral load less than 500 copies/ml and 884 (38%) met criteria for cognitive impairment. Using the customary IHDS cut-off of 10, 1136 (83%) of the HIV-infected participants met criteria for dementia resulting in 91% sensitivity but only 17% specificity. A modified cut-off score of 8 derived from the ROC resulted in low sensitivity (56%) and specificity (64%). CONCLUSION: The IHDS has poor performance characteristics for the identification of cognitive impairment in East Africa. Cultural-informed and sensitive screening tests are needed to detect mild cognitive dysfunctions in developing countries.

Kericho CLinic-based ART Diagnostic Evaluation (CLADE): design, accrual, and baseline characteristics of a randomized controlled trial conducted in predominately rural, district-level, HIV clinics of Kenya.

BACKGROUND: Prospective clinical trial data regarding routine HIV-1 viral load (VL) monitoring of antiretroviral therapy (ART) in non-research clinics of Sub-Saharan Africa are needed for policy makers. METHODS: CLinic-based ART Diagnostic Evaluation (CLADE) is a randomized, controlled trial (RCT) evaluating feasibility, superiority, and cost-effectiveness of routine VL vs. standard of care (clinical and immunological) monitoring in adults initiating dual nucleoside reverse transcriptase inhibitor (NRTI)+non-NRTI ART. Participants were randomized (1:1) at 7 predominately rural, non-research, district-level clinics of western Kenya. Descriptive statistics present accrual patterns and baseline cohort characteristics. RESULTS: Over 15 months, 820 adults enrolled at 7 sites with 86-152 enrolled per site. Monthly site enrollment ranged from 2-92 participants. Full (100%) informed consent compliance was independently documented. Half (49.9%) had HIV diagnosed through voluntary counseling and testing. Study arms were similar: mostly females (57.6%) aged 37.6 (SD = 9.0) years with low CD4 (166 [SD = 106]) cells/m3). Notable proportions had WHO Stage III or IV disease (28.7%), BMI <18.5 kg/m2 (23.1%), and a history of tuberculosis (5.6%) or were receiving tuberculosis treatment (8.2%) at ART initiation. In the routine VL arm, 407/409 (99.5%) received baseline VL (234,577 SD = 151,055 copies/ml). All participants received lamivudine; 49.8% started zidovudine followed by 38.4% stavudine and 11.8% tenofovir; and, 64.4% received nevirapine as nNRTI (35.6% efavirenz). CONCLUSIONS: A RCT can be enrolled successfully in rural, non-research, resource limited, district-level clinics in western Kenya. Many adults presenting for ART have advanced HIV/AIDS, emphasizing the importance of universal HIV testing and linkage-to-care campaigns. TRIAL REGISTRATION: ClinicalTrials.gov NCT01791556.