Persistent Depression and Suicidal Ideation in People Living with HIV in Tanzania: A Longitudinal Cohort Study.

Suicidal ideation and depression are common in people living with HIV (PLWH) in sub-Saharan Africa, but longitudinal data on their persistence in the modern antiretroviral therapy era are lacking. We examined the prevalence of persistent suicidal ideation and depression symptoms using the PHQ-9 in a well-characterized cohort of PLWH and HIV-uninfected community controls. Multivariable logistic regression models were used to determine the relationship between HIV and persistent depression and suicidal ideation. Persistent suicidal ideation was more common in PLWH but there was no difference in persistent depression by HIV status. Approximately one out of five participants with depression at baseline had persistent depression after 12-24 months and only about one out of four participants reporting suicidal ideation at baseline had persistent suicidal ideation after 12-24 months. HIV was associated with suicidal ideation at baseline. Persistent suicidal ideation was significantly associated with HIV immune non-response (p = 0.022). These findings highlight the need for integration of mental health services into HIV care in sub-Saharan Africa with a focus on suicide prevention.

Differentiated service delivery framework for people with multidrug-resistant tuberculosis and HIV co-infection.

INTRODUCTION: For people living with HIV/AIDS, care is commonly delivered through Differentiated Service Delivery (DSD). Although people with multidrug-resistant tuberculosis (MDR-TB) and HIV/AIDS experience severe treatment associated challenges, there is no DSD model to support their treatment. In this study, we defined patterns of medication adherence and characterized longitudinal barriers to inform development of an MDR-TB/HIV DSD framework. METHODS: Adults with MDR-TB and HIV initiating bedaquiline (BDQ) and receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa, were enrolled and followed through the end of MDR-TB treatment. Electronic dose monitoring devices (EDM) measured BDQ and ART adherence. Longitudinal focus groups were conducted and transcripts analyzed thematically to describe discrete treatment stage-specific and cross-cutting treatment challenges. RESULTS: 283 participants were enrolled and followed through treatment completion (median 17.8 months [IQR 16.5-20.2]). Thirteen focus groups were conducted. Most participants (82.7%, 234/283) maintained high adherence (mean BDQ adherence 95.3%; mean ART adherence 85.5%), but an adherence-challenged subpopulation with <85% cumulative adherence (17.3%, 49/283) had significant declines in mean weekly BDQ adherence from 94.9% to 39.9% (p<0.0001) and mean weekly ART adherence from 83.9% to 26.6% (p<0.0001) over 6 months. Psychosocial, behavioral, and structural obstacles identified in qualitative data were associated with adherence deficits in discrete treatment stages, and identified potential stage specific interventions. CONCLUSION: A DSD framework for MDR-TB/HIV should intensify support for adherence-challenged subpopulations, provide multi-modal support for adherence across the treatment course and account for psychosocial, behavioral, and structural challenges linked to discrete treatment stages.

Adaptive evaluation of mHealth and conventional adherence support interventions to optimize outcomes with new treatment regimens for drug-resistant tuberculosis and HIV in South Africa (ADAP-TIV): study protocol for an adaptive randomized controlled trial.

BACKGROUND: Highly effective, short-course, bedaquiline-containing treatment regimens for multidrug-resistant tuberculosis (MDR-TB) and integrase strand transfer inhibitor (INSTI)-containing fixed dose combination antiretroviral therapy (ART) have radically transformed treatment for MDR-TB and HIV. However, without advances in adherence support, we may not realize the full potential of these therapeutics. The primary objective of this study is to compare the effect of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform. METHODS: This is a prospective, adaptive, randomized controlled trial comparing the effectiveness of four adherence support strategies on a composite clinical outcome in adults with MDR-TB and HIV initiating bedaquiline-containing MDR-TB treatment regimens and receiving ART in KwaZulu-Natal, South Africa. Trial arms include (1) enhanced standard of care, (2) psychosocial support, (3) mHealth using cellular-enabled electronic dose monitoring, and (4) combined mHealth and psychosocial support. The level of support will be titrated using a differentiated service delivery (DSD)-informed assessment of treatment support needs. The composite primary outcome will include survival, negative TB culture, retention in care, and undetectable HIV viral load at month 12. Secondary outcomes will include individual components of the primary outcome and quantitative evaluation of adherence on TB and HIV treatment outcomes. DISCUSSION: This trial will evaluate the contribution of different modes of adherence support on MDR-TB and HIV outcomes with WHO-recommended all-oral MDR-TB regimens and ART in a high-burden operational setting. We will also assess the utility of a DSD framework to pragmatically adjust levels of MDR-TB and HIV treatment support. TRIAL REGISTRATION: ClinicalTrials.gov NCT05633056. Registered on 1 December 2022.

Adaptive evaluation of mHealth and conventional adherence support interventions to optimize outcomes with new treatment regimens for drug-resistant tuberculosis and HIV in South Africa (ADAP-TIV): Study protocol for an adaptive randomized controlled trial.

Background: Highly effective, short course, bedaquiline-containing treatment regimens for multidrug-resistant tuberculosis (MDR-TB) and integrase strand transfer inhibitor (INSTI)-containing fixed dose combination antiretroviral therapy (ART) have radically transformed treatment for MDR-TB and HIV. However, without advances in adherence support, we may not realize the full potential of these therapeutics. The primary objective of this study is to compare the effect of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform. Methods: This is a prospective, adaptive, randomized controlled trial comparing the effectiveness of four adherence support strategies on a composite clinical outcome in adults with MDR-TB and HIV initiating bedaquiline-containing MDR-TB treatment regimens and receiving ART in KwaZulu-Natal, South Africa. Trial arms include 1) enhanced standard of care; 2) psychosocial support; 3) mHealth using cellular- enabled electronic dose monitoring; 4) combined mHealth and psychosocial support. The level of support will be titrated using a differentiated service delivery (DSD)-informed assessment of treatment support needs. The composite primary outcome will be include survival, negative TB culture, retention in care and undetectable HIV viral load at month 12. Secondary outcomes will include individual components of the primary outcome and quantitative evaluation of adherence on TB and HIV treatment outcomes. Discussion: This trial will evaluate the contribution of different modes of adherence support on MDR-TB and HIV outcomes with WHO recommended all-oral MDR-TB regimens and ART in a high-burden operational setting. We will also assess the utility of a DSD framework to pragmatically adjust levels of MDR-TB and HIV treatment support.

Sex-dependent correlates of arterial stiffness in Tanzanian adults.

OBJECTIVE: Arterial stiffness is a known indicator for cardiovascular disease. However, the factors that lead to arterial stiffening have primarily been studied in participants from high-income countries. Here, we examine clinical and lifestyle metrics in relation to arterial stiffness in Tanzanian adults. METHODS: We performed pulse wave velocity (PWV), the gold standard measure of arterial stiffness, on 808 Tanzanian adults (ages 18-65) enrolled in a longitudinal cohort studying trends in blood pressure. RESULTS: As expected, PWV was strongly associated with age, blood pressure and sex. We controlled for these factors in our statistical analysis. Lifestyle metrics were compared across multiple PWV quantiles. We found that determinants of PWV varied by sex: in female participants, PWV was associated with common obesity metrics and menopause, while in male participants, PWV was associated with HIV status and duration of anti-retroviral therapy (ART). Further clinical and lifestyle factors such as marriage status and type of occupation were also significantly associated with PWV and moderated by sex. CONCLUSION: Together, our data demonstrate the importance of studying sex-specific causal pathways for arterial stiffness and of including under-represented populations in these studies.

Nocturnal dipping of heart rate and blood pressure in people with HIV in Tanzania.

People with HIV (PWH) have a >2-fold greater risk for development of cardiovascular disease (CVD), which may be associated with abnormalities in 24-h ambulatory blood pressure measurement (ABPM) profile. We conducted a nested case-control study of ABPM in 137 PWH and HIV-uninfected controls with normal and high clinic blood pressure (BP) in Tanzania. Nocturnal non-dipping of heart rate (HR) was significantly more common among PWH than HIV-uninfected controls (p = .01). Nocturnal non-dipping of BP was significantly more common in PWH with normal clinic BP (p = .048). Clinical correlates of nocturnal non-dipping were similar in PWH and HIV-uninfected adults and included higher BMI, higher CD4+ cell count, and high C-reactive protein for HR and markers of renal disease for BP. In conclusion, nocturnal non-dipping of both BP and HR was more common in PWH but further research is needed to determine causes and consequences of this difference.

Blood pressure, T cells, and mortality in people with HIV in Tanzania during the first 2 years of antiretroviral therapy.

Cardiovascular disease is now a leading cause of mortality in people with HIV (PWH). High blood pressure is the major driver of cardiovascular disease. Despite this, little is known about blood pressure in PWH during the early years of antiretroviral therapy (ART). In this prospective cohort study in Tanzania, the authors conducted unobserved blood pressure measurements at enrollment, 3, 6, 12, 18, and 24 months in 500 PWH initiating ART and 504 HIV-uninfected adults. The authors excluded measurements taken on antihypertensive medications. Although PWH had a significantly lower blood pressure before ART initiation, they had a significantly greater increase in blood pressure during the first 2 years of ART compared to HIV-uninfected controls. Blood pressure correlates in PWH differed from HIV-uninfected controls. In PWH, lower baseline CD4+ T-cell counts were associated with lower blood pressure, and greater increases in CD4+ T-cell counts on ART were associated with greater increases in blood pressure, both on average and within individuals. In addition, PWH with a systolic blood pressure (SBP) <90 mm Hg at the time of ART initiation had ~30% mortality in the following 3 months due to occult infections. These patients require careful investigation for occult infections, and those with tuberculosis may benefit from corticosteroids.

Hypertensive Urgency in Tanzanian Adults: A 1-Year Prospective Study.

BACKGROUND: Hypertensive urgency is associated with a high risk for cardiovascular events and mortality in the United States and Europe, but data from low-income countries and interventions to improve outcomes are lacking. METHODS: We conducted a 1-year prospective study of the prevalence and outcomes of hypertensive urgency (blood pressure (BP) ≥180 mm Hg/120 mm Hg without end-organ damage) in a busy outpatient clinic in Tanzania. RESULTS: Of 7,600 consecutive adult outpatients screened with 3 unattended automated BP measurements according to standard protocol, the prevalence of hypertensive crisis was 199/7,600 (2.6%) (BP ≥180 mm Hg/120 mm Hg) and the prevalence of hypertensive urgency was 164/7,600 (2.2%). Among 150 enrolled patients with hypertensive urgency, median age was 62 years (54-68), 101 (67.3%) were women, and 53 (35%) were either hospitalized or died within 1 year. In a multivariate model, the strongest predictor of hospitalization/death was self-reported medication adherence on a 3 question scale (hazard ratio: 0.06, P < 0.001); 90% of participants with poor adherence were hospitalized or died within 1 year. CONCLUSIONS: Patients with hypertensive urgency in Africa are at high risk of poor outcomes. Clinicians can identify the patients at highest risk for poor outcomes with simple questions related treatment adherence. New interventions are needed to improve medication adherence in patients with hypertensive urgency.

Renal abnormalities and its associated factors among school-aged children living in Schistosoma mansoni endemic communities in Northwestern Tanzania.

BACKGROUND: In sub-Saharan Africa, renal abnormalities are a major public health concern, especially in children living in Schistosoma haematobium endemic areas. However, there is a dearth of data on renal abnormalities among children living in Schistosoma mansoni endemic areas. The objective of the study was to assess the prevalence of renal abnormalities among school children in a Schistosoma mansoni endemic community in Northwestern Tanzania. METHODS: A cross-sectional study was conducted between January and March 2017 among school children aged 6-13 years, attending three primary schools located along the shoreline of Lake Victoria. A single urine sample was collected from each child and screened for S. mansoni using circulating cathodic antigen and for S. haematobium eggs using a urine filtration technique. A urine dipstick was used to screen for urine protein levels, creatinine levels, microalbuminuria, and red blood cells. Venous blood was obtained for estimation of creatinine level and for malaria diagnosis. The primary outcomes were the prevalence of renal abnormalities, defined by the presence of low estimated glomerular filtration rate (eGFR), proteinuria or microalbuminuria, and hematuria in urine. RESULTS: Of 507 children included in the final analysis, 49.9% (253/507) were male with a mean age of 8.51 ± 1.3 years. Overall, 64.0% (326/507) of the children were infected with S. mansoni, and 1.6% (8/507) of the children were infected with S. haematobium. A total of 71 (14%) of the children had proteinuria, 37 (7.3%) had hematuria, and 8 (1.6%) had a low estimated glomerular filtration rate (eGFR). Overall prevalence of renal abnormalities was 22.9%. Renal abnormalities (proteinuria) were associated with S. mansoni infection (OR = 4.9, 95% CI 2.1-11.2, p < 0.001) and having red blood cells in urine (OR = 5.3, 95% CI 2.5-11.2, p < 0.001). CONCLUSION: Twenty-two percent of school children who participated in this study had renal abnormalities associated with S. mansoni infection. Given the high prevalence of S. mansoni, longitudinal epidemiological surveillance is warranted to measure the burden of renal abnormalities and assess the impact of the praziquantel treatment on these abnormalities.

Diabetic Microvascular Complications Among Children and Adolescents in Northwestern Tanzania: A Cross-Sectional Study.

Background: Africa is experiencing a rapid increase in morbidity and mortality related to diabetes mellitus (DM). Contemporary data are needed to guide efforts to improve prevention and treatment for microvascular complications in children and adolescents in Africa. This study was conducted to assess prevalence of diabetic microvascular complications in northwestern Tanzania, including nephropathy, retinopathy, and neuropathy, as well as associated risk factors. Objectives: 1) To determine the prevalence of microvascular complications and the overlap of nephropathy, retinopathy and neuropathy and 2) to determine factors associated with the development of microvascular complications. Methods: This cross-sectional study included 155 children and adolescents with DM consecutively attending all three health centers providing diabetes care for children in the Mwanza region of Tanzania. Participants were examined for microvascular complications and possible risk factors. Results: Fifty-one of 155 participants (age: 5-19 years) had diabetic nephropathy (32.9%), 16 had diabetic retinopathy (10.3%), and 21 had diabetic neuropathy (13.6%). Risk factors for development of a microvascular complication included age, duration of DM, and poor glycemic control. Of the participants, 107 had poor levels of glycemic control (69%) with HbA1C levels >10%. Conclusion: The prevalence of microvascular complications, especially that of nephropathy, was disturbingly high. Risk factors for microvascular complications were similar to other studies from Africa and included poor glycemic control, older age, and longer duration of DM. Innovative, locally appropriate systems for optimizing glycemic control are urgently needed.