Persistent High Burden and Mortality Associated With Advanced HIV Disease in Rural Tanzania Despite Uptake of World Health Organization "Test and Treat" Guidelines.

Background: Information about burden, characteristics, predictors, and outcomes of advanced human immunodeficiency virus disease (AHD) is scarce in rural settings of sub-Saharan Africa. Human immunodeficiency virus (HIV) infections and associated deaths remain high despite specific guidelines issued by the World Health Organization (WHO). Methods: Burden of AHD and 6-month death/loss to follow-up (LTFU) were described among 2498 antiretroviral therapy (ART)-naive nonpregnant people with HIV (PWH) aged >15 years enrolled in the Kilombero Ulanga Antiretroviral Cohort in rural Tanzania between 2013 and 2019. Baseline characteristics associated with AHD and predictors of death/LTFU among those with AHD were analyzed using multivariate logistic and Cox regression, respectively. Results: Of the PWH, 62.2% had AHD at diagnosis (66.8% before vs 55.7% after national uptake of WHO "test and treat" guidelines in 2016). At baseline, older age, male sex, lower body mass index, elevated aminotransferase aspartate levels, severe anemia, tachycardia, decreased glomerular filtration rate, clinical complaints, impaired functional status, and enrollment into care before 2018 were independently associated with AHD. Among people with AHD, incidence of mortality, and LTFU were 16 and 34 per 100 person-years, respectively. WHO clinical stage 3 or 4, CD4 counts <100 cells/µL, severe anemia, tachypnea, and liver disease were associated with death/LTFU. Conclusions: More than 50% of PWH enrolled in our cohort after test and treat implementation still had AHD at diagnosis. Increasing HIV testing and uptake and implementation of the WHO-specific guidelines on AHD for prevention, diagnosis, treatment of opportunistic infections, and reducing the risks of LTFU are urgently needed to reduce morbidity and mortality.

Failure to return pillbox is a predictor of being lost to follow-up among people living with HIV on antiretroviral therapy in rural Tanzania.

OBJECTIVES: Pill count is used to assess drug adherence in people living with HIV (PLHIV). Carrying a pillbox is associated with fear of concealment and stigma and might indicate poor adherence and predict someone who will be lost to follow-up (LTFU). We therefore assessed the association between pillbox return and being LTFU in rural Tanzania. METHODS: This is a nested study of the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). We included PLHIV aged ≥ 18 years enrolled in KIULARCO between January 2013 and March 2019 with follow-up through January 2020, who were on antiretroviral treatment (ART) for ≥ 6 months. Baseline was defined as the latest ART initiation or KIULARCO enrolment. We determined the association between time-dependent failed pillbox return updated at every visit and LTFU using Kaplan-Meier estimation and Cox models. RESULTS: Among 2552 PLHIV included in the study, 1735 (68.0%) were female, 959 (40.3%) had a WHO stage III/IV and 1487 (66.4%) had a CD4 cell count < 350 cells/µL. The median age was 38.4 years [interquartile range (IQR): 31.7-46.2]. During a median follow-up of 33.1 months (IQR: 17.5-52.4), 909 (35.6%) participants were LTFU, 43 (1.7%) died and 194 (7.6%) had transferred to another clinic. The probability of being LTFU was higher among PLHIV with failed pillbox return than among those who returned their pillbox [30.0%, 95% confidence interval (CI): 26.8-33.2% vs. 19.4%, 95% CI: 17.4-21.6%, respectively, at 24 months (hazard ratio = 1.67, 95% CI: 1.46-1.90; p < 0.001)]. CONCLUSIONS: Failed pillbox return was associated with a higher risk of being LTFU and could be used as a simple tool to identify PLHIV for appropriate interventions to reduce their chance of being LTFU.

Prospective assessment of loss to follow-up: incidence and associated factors in a cohort of HIV-positive adults in rural Tanzania.

INTRODUCTION: Lifelong antiretroviral therapy (ART) improves health outcomes for HIV-positive individuals, but is jeopardized by irregular clinic attendance and hence poor adherence. Loss to follow-up (LTFU) is typically defined retrospectively but this may lead to biased inferences. We assessed incidence of and factors associated with LTFU, prospectively and accounting for recurrent LTFU episodes, in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) of HIV-positive persons in rural Tanzania. METHODS: We included adults (≥15 years) enrolled in 2005 to 2016, regardless of ART status, with follow-up through April 2017. LTFU was defined as >60 days late for a scheduled appointment. Participants could experience multiple LTFU episodes. We performed analyses based on the first (prospective) and last (retrospective) events observed during follow-up, and accounting for recurrent LTFU episodes. Time to LTFU was estimated using cumulative incidence functions. We assessed factors associated with LTFU using cause-specific proportional hazards, marginal means/rates, and Prentice, Williams and Peterson models. RESULTS: Among 8087 participants (65% female, 60% aged ≥35 years, 42% WHO stage 3/4, and 47% CD4 count <200 cells/mm3 ), there were 8140 LTFU episodes, after which there were 2483 (31%) returns to care. One-year LTFU probabilities were 0.41 (95% confidence interval 0.40, 0.42) and 0.21 (0.20, 0.22) considering the first and last events respectively. Factors associated with LTFU were broadly consistent across different models: being male, younger age, never married, living far from the clinic, not having an HIV-positive partner, lower BMI, advanced WHO stage, not having tuberculosis, and shorter time since ART initiation. Associations between LTFU and pregnancy, CD4 count, and enrolment year depended on the analysis approach. CONCLUSIONS: LTFU episodes were common and prompt tracing efforts are urgently needed. We identified socio-demographic and clinical characteristics associated with LTFU that can be used to target tracing efforts and to help inform the design of appropriate interventions. Incidence of and risk factors for LTFU differed based on the LTFU definition applied, highlighting the importance of appropriately accounting for recurrent LTFU episodes. We recommend using a prospective definition of LTFU combined with recurrent event analyses in cohorts where repeated interruptions in care are common.

Vitamin D Concentration during Early Pregnancy and Adverse Outcomes among HIV-Negative Women in Dar-es-Salaam, Tanzania: A Case-Control Study.

We examined the associations of plasma vitamin D concentration and adverse pregnancy outcomes among HIV-negative women in Dar-es-Salaam, Tanzania. We used an unmatched case-control study design, with 25-hydroxyvitamin D [25(OH)D] concentration assessed in the first trimester. Cases were individuals with adverse pregnancy outcomes, including stillbirth, premature birth, or small for gestational age births (SGA). Unconditional logistic regression and weighted logistic regression models were used to describe the associations of 25(OH)D concentration with the composite of adverse pregnancy outcome and individual adverse pregnancy outcomes, respectively. We included 310 cases and 321 controls. In controls, 5(2%) were vitamin D deficient (25(OH)D < 20 ng/mL), and 17(5%) had insufficient 25(OH)D concentration (20.0-29.9 ng/mL). Women with 25(OH)D < 20 ng/mL had 1.82 times the odds of occurrence of the composite adverse pregnancy outcome (OR = 1.82, 95% CI: 0.56-5.93; p = 0.32), however we noted a non-linear association between 25(OH)D concentration and adverse pregnancy outcome (p = 0.02). We found a 3-fold increased odds of stillbirth in women with low 25(OH)D concentration (OR = 3.11, 95% CI: 1.18-8.23, p = 0.02). Vitamin D concentration in early pregnancy may be an important factor in determining the course of pregnancy. Further research is needed to investigate whether the association of maternal 25(OH)D concentration in early pregnancy and stillbirth is causal.

Prevalence and Evolution of Renal Impairment in People Living With HIV in Rural Tanzania.

BACKGROUND: We assessed the prevalence, incidence, and predictors of renal impairment among people living with HIV (PLWHIV) in rural Tanzania. METHODS: In a cohort of PLWHIV aged ≥15 years enrolled from January 2013 to June 2016, we assessed the association between renal impairment (estimated glomerural filtration rate < 90 mL/min/1.73 m2) at enrollment and during follow-up with demographic and clinical characteristcis using logistic regression and Cox proportional hazards models. RESULTS: Of 1093 PLWHIV, 172 (15.7%) had renal impairment at enrollment. Of 921 patients with normal renal function at baseline, 117 (12.7%) developed renal impairment during a median follow-up (interquartile range) of 6.2 (0.4-14.7) months. The incidence of renal impairment was 110 cases per 1000 person-years (95% confidence interval [CI], 92-132). At enrollment, logistic regression identified older age (adjusted odds ratio [aOR], 1.79; 95% CI, 1.52-2.11), hypertension (aOR, 1.84; 95% CI, 1.08-3.15), CD4 count <200 cells/mm3 (aOR, 1.80; 95% CI, 1.23-2.65), and World Health Organization (WHO) stage III/IV (aOR, 3.00; 95% CI, 1.96-4.58) as risk factors for renal impairment. Cox regression model confirmed older age (adjusted hazard ratio [aHR], 1.85; 95% CI, 1.56-2.20) and CD4 count <200 cells/mm3 (aHR, 2.05; 95% CI, 1.36-3.09) to be associated with the development of renal impairment. CONCLUSIONS: Our study found a low prevalence of renal impairment among PLWHIV despite high usage of tenofovir and its association with age, hypertension, low CD4 count, and advanced WHO stage. These important and reassuring safety data stress the significance of noncommunicable disease surveillance in aging HIV populations in sub-Saharan Africa.