Effect of high-dose multivitamin supplements on alanine aminotransferase elevations among adults living with HIV on antiretroviral therapy in Tanzania.

BACKGROUND: HIV infection can cause malabsorption and rapid utilization of nutrients. A randomized trial of multivitamin supplementation among people living with HIV/AIDS (PLWHA) initiating antiretroviral therapy (ART) in Tanzania was stopped early due to increased alanine aminotransferase (ALT) concentrations in the multiple recommended dietary allowances (RDA) multivitamin group. We conducted detailed analysis to assess the effect of multivitamins on ALT elevations and evaluate whether subgroups of PLWHA have greater hepatotoxicity risks associated with the use of high-dose multivitamins. METHODS: We utilized data from a randomized, double-blind trial conducted in 2006-2009 that assessed the effect of high-dose multivitamins that contained vitamin B complex, vitamin C, and vitamin E at multiple RDA as compared to standard-dose multivitamins containing single RDAs among adults initiating ART in Tanzania. We evaluated the effect of high-dose multivitamins on incident mild/moderate ALT elevations > 40 IU/L, persistent ALT elevations > 40 IU/L (2 + clinic visits), and severe ALT elevations > 200IU/L using Cox proportional hazard models. We then evaluated effect modification by patient characteristics to determine if subgroups of PLWHA experienced different magnitudes of risk for ALT elevations associated with high-dose multivitamins. RESULTS: High-dose multivitamins increased the risk of incident mild/moderate ALT elevations > 40 IU/mL as compared to standard-dose multivitamins (hazard ratio (HR): 1.41; 95%CI: 1.26,1.58) as well as incident sustained mild/moderate ALT elevations (HR: 1.19; 95%CI: 1.04,1.36), but there was no overall effect on severe ALT elevations (HR: 1.44; 95% CI: 0.91,2.28). There was no evidence that the effect of high-dose multivitamins on any or sustained mild/moderate ALT elevations was modified by any patient characteristic. However, CD4 T-cell count was found to modify the effect of high-dose multivitamins on severe ALT elevations (p-value for interaction:0.01). Among participants with a baseline CD4 T-cell count ≤ 100 cells/µL, individuals receiving high-dose multivitamins had 3.74 times (95%CI: 1.52-9.17) the risk of incident severe ALT elevations compared to standard-dose multivitamins, while participants with CD4 T-cell counts > 100 cells/µL, appeared to have no effect of high-dose multivitamins on severe ALT elevations (HR:0.92; 95% CI: 0.50,1.67). CONCLUSIONS: High-dose RDA multivitamin supplementation increased the incidence of any mild to moderate ALT elevations among adults starting ART in Tanzania and the magnitude of the risk does not appear to differ by patient characteristics. However, immunocompromised PLWHA with CD4 T-cell counts < 100 cells/µL may experience greater risk of severe ALT elevations associated with the use of high-dose multivitamins. Although the study findings offer significant insights, it is essential to take into account limitations imposed by newer cART regimes.

'I am happy to be listened to': co-creation of a simple tool to measure women's experiences of respectful maternity care in urban Tanzania.

BACKGROUND: Rights-based Respectful Maternity Care (RMC) is crucial for quality of care and improved birth outcomes, yet RMC measurements are rarely included in facility improvement initiatives. We aimed to (i) co-create a routine RMC measurement tool (RMC-T) for congested maternity units in Dar es Salaam, Tanzania, and (ii) assess the RMC-T's acceptability among women and healthcare stakeholders. METHOD: We employed a participatory approach utilizing multiple mixed methods. This included a scoping review, stakeholder engagement involving postnatal women, healthcare providers, health leadership, and global researchers through interviews, focus groups, and two surveys involving 201 and 838 postnatal women. Cronbach's alpha and factor analysis were conducted for validation using Stata 15. Theories of social practice and Thematic Framework of Acceptability guided the assessment of stakeholder priorities and tool acceptability. RESULTS: The multi-phased iterative co-creation process produced the 25-question RMC-T that measures satisfaction, communication, mistreatment (including physical, verbal, and sexual abuse; neglect; discrimination; lack of privacy; unconsented care; post-birth clean-up; informal payments; and denial of care), supportive care (such as food intake and mobility), birth companionship, post-procedure pain relief, bed-sharing, and newborn respect. The pragmatic validation process prioritized stakeholder feedback over strict statistics, lowering Cronbach's alpha from 0.70 in version 1 to 0.57 for the RMC-T. Women valued the opportunity to share their experiences. CONCLUSIONS: The RMC-T is contextualized, validated, and acceptable for measuring women's experiences of RMC. Routine use in facility-based quality improvement initiatives, along with targeted actions to address gaps, will advance rights-based RMC. Further validation and community-based studies are needed.

• Main findings: This study describes the participatory approach involving postnatal women, healthcare providers, health leadership, and global researchers to co-create and validate a tool for measuring women's experiences of respectful maternity care in Dar es Salaam's urban health facilities.• Added knowledge: The iterative process produced a concise, 25-item Respectful Maternity Care Measurement tool that is user-friendly, administered in 15­20 minutes and addresses all mistreatment domains. The tool reflects women's priorities and is well accepted by postnatal women and health leaders.• Global health impact for policy and action: Regular use of the tool can enhance awareness of childbirth rights and drive actions to improve and normalize respectful maternity care in low-resource urban settings.

Trends and correlates in HIV viral load monitoring and viral suppression among adolescents and young adults in Dar es Salaam, Tanzania.

BACKGROUND: Adolescents and young adults (AYA) living with HIV have been shown to have lower rates of viral load testing and viral suppression as compared to older adults. We examined trends over time and predictors of HIV viral load monitoring and viral suppression among AYA in a large HIV treatment programme in Dar es Salaam, Tanzania. METHODS: We analysed longitudinal data of AYA aged 10-24 years initiated on antiretroviral therapy between January 2017 and October 2022. Trend models were used to assess changes in HIV viral load testing and viral suppression by calendar year. Generalised estimating equations were used to examine the relationship of sociodemographic and clinical factors with HIV viral load testing and viral suppression. RESULTS: Out of 15,759 AYA, the percentage of those who received a 6-month HIV viral load testing increased from 40.6% in 2017 to 64.7% in 2022 and, a notable annual increase of 5.6% (p < 0.001). A higher HIV viral load testing uptake was observed among 20- to 24-year-olds (87.7%) compared to 10- to 19-year-olds (80.2%) (p < 0.001). The likelihood of not receiving an HIV viral load test within 12 months of antiretroviral therapy initiation was higher among 10- to 19-year-olds (adjusted odds ratio [aOR] = 1.7; 95% confidence interval [CI] = 1.4-2.0), advanced HIV disease (aOR = 1.3; 95% CI = 1.12-1.53), normal nutrition status at enrolment aOR 2.6 (95% CI = 1.59-4.26) and initiation of non-nucleoside reverse transcriptase inhibitors regimen aOR 1.2 (95% CI = 1.08-1.34). The proportion of AYA with viral suppression increased from 83.0% in 2017 to 94.6% in 2022. Notably, the overall trend in viral suppression increased significantly at 2.4% annually. The risk of not achieving viral suppression was greater among 10- to 14-year-olds (aOR = 2; 95% CI = 1.75-2.43) and 15- to 19-year-olds (aOR = 1.4; 95% CI = 1.24-1.58) as compared to 20-24 years; being male (aOR = 1.16; 95% CI = 1.02-1.32); undernourished (aOR = 1.53; 95% CI = 1.17-1.99); in WHO Stage II (aOR = 1.16; 95% CI = 1.02-1.33) and III (aOR = 1.21; 95% CI = 1.03-1.42) and being on an non-nucleoside reverse transcriptase inhibitors regimen (aOR = 1.32; 95% CI = 1.18-1.48). CONCLUSION: HIV viral load testing uptake at 6 months of antiretroviral therapy initiation and viral suppression increased from 2017 to 2022; however, overall HIV viral load testing was suboptimal. Demographic and clinical characteristics can be used to identify AYA at greater risk for not having HIV viral load test and not achieving viral suppression.

School health and nutrition services for children and adolescents in Tanzania: A review of policies and programmes.

School health and nutrition programmes are effective strategies to address the health problems among school-going children and adolescents. We examined the policy environments, successes and bottlenecks associated with school health and nutrition programmes in Tanzania. We used the 'policy triangle framework' to examine 22 national and regional school health and nutrition policies and programmes in Tanzania. We also interviewed 16 key informants to gain further insights into school health and nutrition programmes. Several school health and nutrition policies in Tanzania outline the basic elements of school-based health and nutrition services. Yet, these documents neither recognise vulnerable groups, recommend age-appropriate strategies to address children's and adolescents' varied and transient needs, nor provide a framework for implementing and tracking recommended activities. In these documents, underweight and infectious diseases, including human immunodeficiency virus/acquired immunodeficiency syndrome, are frequently identified as major concerns of young people, with little or no consideration of social determinants. Diverse strategies including school feeding, water and sanitation services, health and nutrition education and promotion of healthy behaviours are identified. In doing so, these documents adequately define the roles and responsibilities of all government actors, but young people and their guardians are not actively engaged in design and implementation. Additionally, there are several challenges to implementing these policies including budgetary constraints, limited resources, a lack of inter-sectoral coordination and insufficient capacity within targeted schools. To improve the health and nutritional status of school-going children and adolescents in Tanzania, adequate budgets, strengthened coordination and implementation efforts, the development of school-based stakeholders' capacity, as well as the involvement of all other stakeholders, including adolescents, are imperative.

Resistance-informed versus empirical management of viraemia in children and adolescents with HIV in Lesotho and Tanzania (GIVE MOVE trial): a multisite, open-label randomised controlled trial.

BACKGROUND: Children and adolescents with HIV taking antiretroviral therapy (ART) have high rates of viraemia. We assessed if genotypic resistance testing (GRT) to inform onward treatment improved treatment outcomes in Lesotho and Tanzania, two countries with little access to GRT. METHODS: The Genotype-Informed Versus Empirical Management of Viremia (GIVE MOVE) open-label, parallel-group randomised controlled trial enrolled children and adolescents with HIV between the ages of 6 months and 19 years, taking ART, and with a viral load at least 400 copies per mL. Participants were recruited from ten clinical centres and hospitals in Lesotho and Tanzania. Participants were electronically randomly allocated 1:1 to receive either GRT with expert recommendation (GRT group) or repeat viral-load testing and empirical onward treatment (usual care group). Participants and study staff were not masked, but the endpoint committee and laboratory staff conducting viral-load testing were. Participants in both groups received at least three sessions of enhanced adherence counselling, and in the GRT group, blood for GRT assessed via Sanger sequencing was drawn at enrolment. The composite primary endpoint was death, hospitalisation, a new WHO HIV clinical stage 4 event, or not having documented viral suppression of less than 50 copies per mL at 36 weeks in the modified intention-to-treat population, which excluded participants who were retrospectively found to be ineligible after randomisation. Serious adverse events were analysed in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT04233242) and the trial status is completed. FINDINGS: Between March 3, 2020, and July 5, 2022, 286 participants were enrolled and 284 were included in the modified intention-to-treat analysis (144 in the GRT group and 140 in the usual care group). Of these participants, 158 (56%) were female and 126 (44%) were male. Five (3%) in the GRT group and four (3%) in the usual care group did not complete follow-up but were included in the primary analysis. The median age across both groups was 14 years (IQR 9-16). The composite primary endpoint occurred in 67 (47%) participants in the GRT group and 73 (52%) in the usual care group (adjusted odds ratio 0·79 [95% CI 0·49 to 1·27]; adjusted risk difference -0·06 [95% CI -0·17 to 0·06]; p=0·34); all participants reaching the composite primary endpoint had no documented viral suppression at 36 weeks. No deaths were recorded, and only one clinical stage 4 event requiring hospitalisation occurred (in the usual care group); this was the only serious adverse event recorded in the study. INTERPRETATION: GRT-informed management did not significantly improve treatment outcomes for children and adolescents with viraemia while taking ART. FUNDING: Fondation Botnar, Swiss National Science Foundation, and Gottfried and Julia Bangerter-Rhyner Foundation. TRANSLATIONS: For the Sesotho and Swahili translations of the abstract see Supplementary Materials section.

Emotional and cognitive influences on alcohol consumption in middle-aged and elderly Tanzanians: a population-based study.

Alcohol consumption in Tanzania exceeds the global average. While sociodemographic difference in alcohol consumption in Tanzania have been studied, the relationship between psycho-cognitive phenomena and alcohol consumption has garnered little attention. Our study examines how depressive symptoms and cognitive performance affect alcohol consumption, considering sociodemographic variations. We interviewed 2299 Tanzanian adults, with an average age of 53 years, to assess their alcohol consumption, depressive symptoms, cognitive performance, and sociodemographic characteristics using a zero-inflated negative binomial regression model. The logistic portion of our model revealed that the likelihood alcohol consumption increased by 8.4% (95% confidence interval [CI] 3.6%, 13.1%, p < 0.001) as depressive symptom severity increased. Conversely, the count portion of the model indicated that with each one-unit increase in the severity of depressive symptoms, the estimated number of drinks decreased by 2.3% (95% CI [0.4%, 4.0%], p = .016). Additionally, the number of drinks consumed decreased by 4.7% (95% CI [1.2%, 8.1%], p = .010) for each increased cognitive score. Men exhibited higher alcohol consumption than women, and Christians tended to consume more than Muslims. These findings suggest that middle-aged and elderly adults in Tanzania tend to consume alcohol when they feel depressed but moderate their drinking habits by leveraging their cognitive abilities.

Demonstrating service delivery models for effective initiation and retention on pre-exposure prophylaxis (PrEP) among female bar workers in Dar es Salaam, Tanzania: A double randomized intervention study protocol.

BACKGROUND: Pre-Exposure Prophylaxis (PrEP) has demonstrated efficacy in preventing HIV infection. Female Bar Workers (FBWs) often act as informal sex workers, placing them at risk of HIV infection. Despite expressing interest in PrEP, FBWs face barriers to accessing public-sector clinics where PrEP is delivered. We developed a study to compare the effectiveness of workplace-based PrEP provision to standard-of-care facility-based provision for PrEP initiation, retention and adherence among FBWs. METHODS: In this double-randomized intervention study, FBWs aged 15 years and above will be screened, consented and initiated on PrEP (emtricitabine/tenofovir disoproxil), and followed for six months. Participants will be randomized at the bar level and offered PrEP at their workplace or at a health facility. Those who are initiated will be independently individually randomized to either receive or not receive an omni-channel PrEP champion intervention (support from an experienced PrEP user) to improve PrEP adherence. We expect to screen 1,205 FBWs to enroll at least 160 HIV negative women in the study. Follow-up visits will be scheduled monthly. HIV testing will be performed at baseline, month 1, 4 and 6; and TDF testing at months 2 and 6. Primary outcomes for this trial are: (1) initiation on PrEP (proportion of those offered PrEP directly observed to initiate PrEP); and (2) adherence to PrEP (detectable urine TDF drug level at 6-months post-enrollment). The primary outcomes will be analyzed using Intention-to-Treat (ITT) analyses. DISCUSSION: Using a randomized trial design, we will evaluate two interventions aiming to reduce barriers to uptake and retention on PrEP among FBWs, a vulnerable population at risk of HIV acquisition and onward transmission. If these interventions prove effective in promoting PrEP among FBWs, they could assist in abating the HIV epidemic in Africa. TRIAL REGISTRATION: Registered with German Clinical Trials Register (www.drks.de) on 29 April 2020; Registration number DRKS00018101.

Accelerating COVID-19 Vaccination Among People Living With HIV and Health Care Workers in Tanzania: A Case Study.

BACKGROUND: There is limited evidence on COVID-19 vaccination uptake among people living with HIV (PLHIV) and health care workers (HCWs), with the current evidence concentrated in high-income countries. There is also limited documentation in the published literature regarding the feasibility and lessons from implementing targeted vaccination strategies to reach PLHIV and HCWs in low- and middle-income countries. PROGRAM DEVELOPMENT, PILOTING, AND IMPLEMENTATION: We designed and implemented multifaceted strategies to scale up targeted COVID-19 vaccination among PLHIV and HCWs in 11 administrative regions on the mainland of Tanzania plus Zanzibar. An initial 6-week intensification strategy was implemented using a diverse partnership model comprising key stakeholders at the national- and subnational levels. A layered package of strategies included expanding the number of certified vaccinators, creating vaccination points within HIV clinics, engaging HCWs to address their concerns, and building the capacity of HCWs as "champions" to promote and facilitate vaccination. We then closely monitored COVID-19 vaccination uptake in 562 high-volume HIV clinics. Between September 2021 and September 2022, the proportion of fully vaccinated adult PLHIV increased from <1% to 97% and fully vaccinated HCWs increased from 23% to 80%. LESSONS AND IMPLICATIONS: Our intra-action review highlighted the importance of leveraging a strong foundation of existing partnerships and platforms, integrating COVID-19 vaccination points within HIV clinics, and refining strategies to increase vaccination demand while ensuring continuity of vaccine supply to meet the increased demand. Lessons from Tanzania can inform targeted vaccination of vulnerable groups in future health emergencies.

Anemia and Iron Supplementation in Relation to Viral Load and Mortality among 70,442 People Living with Human Immunodeficiency Virus in Tanzania.

BACKGROUND: Anemia may be associated with poor clinical outcomes among people living with human immunodeficiency virus (HIV) (PLHIV) despite highly active antiretroviral therapy (HAART). There are concerns that iron supplementation may be unsafe to prevent and treat anemia among PLHIV. OBJECTIVE: The objective of the study was to evaluate the associations of anemia and iron supplementation with mortality and viral load among PLHIV in Tanzania. METHODS: We analyzed data from a cohort of 70,442 nonpregnant adult PLHIV in Tanzania conducted between 2015 and 2019. Regression models evaluated the relationships between anemia severity and iron supplement use with mortality and unsuppressed HIV-1 viral load among all participants and stratified by whether participants were initiating or continuing HAART. RESULTS: Anemia was associated with an increased risk of mortality and unsuppressed viral load for participants who initiated or continued HAART. Iron supplement use was associated with reduced mortality risk but also had a greater risk of an unsuppressed viral load among participants continuing HAART. There was no association of iron supplement use with mortality, and unsuppressed viral load among PLHIV that were initiating HAART. There was a stronger negative association between iron supplement use and the risk of having an unsuppressed viral load among participants with stage III/IV disease compared with stage I/II disease. CONCLUSIONS: Anemia is associated with increased risk of mortality and unsuppressed viral load, but the benefits and safety of iron supplements appear to differ for those initiating compared with continuing ART as well as by HIV disease severity.

Social network strategy (SNS) for HIV testing: a new approach for identifying individuals with undiagnosed HIV infection in Tanzania.

Social network strategy (SNS) testing uses network connections to refer individuals at high risk to HIV testing services (HTS). In Tanzania, SNS testing is offered in communities and health facilities. In communities, SNS testing targets key and vulnerable populations (KVP), while in health facilities it complements index testing by reaching unelicited index contacts. Routine data were used to assess performance and trends over time in PEPFAR-supported sites between October 2021 and March 2023. Key indicators included SNS social contacts tested, and new HIV-positives individuals identified. Descriptive and statistical analysis were conducted. Univariable and multivariable analysis were applied, and variables with P-values <0.2 at univariable analysis were considered for multivariable analysis. Overall, 121,739 SNS contacts were tested, and 7731 (6.4%) previously undiagnosed individuals living with HIV were identified. Tested contacts and identified HIV-positives were mostly aged ≥15 years (>99.7%) and females (80.6% of tests, 79.4% of HIV-positives). Most SNS contacts were tested (78,363; 64.7%) and diagnosed (6376; 82.5%) in communities. SNS tests and HIV-positives grew 11.5 and 6.1-fold respectively, from October-December 2021 to January-March 2023, with majority of clients reached in communities vs. facilities (78,763 vs. 42,976). These results indicate that SNS testing is a promising HIV case-finding approach in Tanzania.

Long-term retention on antiretroviral treatment after enrolment in prevention of vertical HIV transmission services: a prospective cohort study in Dar es Salaam, Tanzania.

INTRODUCTION: To prevent vertical HIV transmission and ensure healthy mothers and children, pregnant women with HIV must remain on antiretroviral treatment (ART) for life. However, motivation to remain on ART may decline beyond the standard 2-year breastfeeding/postpartum period. We assessed attrition and retention in ART care among women with HIV up to 6 years since enrolment in vertical transmission prevention services in Dar es Salaam, Tanzania. METHODS: A prospective cohort of 22,631 pregnant women with HIV were enrolled in vertical transmission prevention services between January 2015 and December 2017 in routine healthcare settings and followed-up to July 2021. Kaplan-Meier was used to estimate time to ART attrition (died, stopped ART or was lost to follow-up [no show ≥90 days since scheduled appointment]) and the proportion retained in care. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) of ART attrition in relation to predictors. RESULTS: Participants were followed-up to 6 years for a median of 3 years (IQR: 0.1-4). The overall ART attrition rate was 13.8 per 100 person-years (95% CI: 13.5-14.1), highest in the first year of enrolment at 27.1 (26.3-27.9), thereafter declined to 9.5 (8.9-10.1) in year 3 and 2.7 (2.1-3.5) in year 6. The proportion of women retained in care were 78%, 69%, 63%, 60%, 57% and 56% at 1, 2, 3, 4, 5 and 6 years, respectively. ART attrition was higher in young women aged <20 years (aHR 1.63, 95% CI: 1.38-1.92) as compared to 30-39 year-olds and women enrolled late in the third versus first trimester (aHR 1.29, 95% CI: 1.16-1.44). In contrast, attrition was lower in older women ≥40 years, women who initiated ART before versus during the index pregnancy and women attending higher-level health facilities. CONCLUSIONS: ART attrition among women with HIV remains highest in the first year of enrolment in vertical transmission prevention services and declines markedly following a transition to chronic HIV care. Targeted interventions to improve ART continuity among women with HIV during and beyond prevention of vertical transmission are vital to ending paediatric HIV and keeping women and children alive and healthy.

High viral suppression and detection of dolutegravir-resistance associated mutations in treatment-experienced Tanzanian adults living with HIV-1 in Dar es Salaam.

To curb HIV infection rate in Tanzania, antiretroviral therapy (ART) has been scaled up since 2006, and in 2019, the country shifted to regimen including dolutegravir as a default first line. We assessed the success of ART and the contribution of HIV drug resistance (HIVDR) to unsuppressed viral loads. Between February and May 2023 a cross-sectional survey with random sampling was conducted in the six clinics in an urban cohort in Dar es Salaam. Patients with unsuppresed viral loads (local criteria viral load (VL) ≥ 1000 copies/mL) were tested for HIVDR mutations using the WHO adapted protocol for plasma samples. Mutations were interpreted using the Stanford HIVDR database. In total 600 individuals participated in this survey, the majority were female (76.83%), mean age ([Formula: see text] standard deviation) was 44.0 ([Formula: see text] 11.6) years. The median duration on ART (interquartile range) was 6.5 (3.9-10.2) years. Approximately 99% were receiving tenofovir + lamivudine + dolutegravir as a fixed dose combination. VL testing was successful in 99.67% (598/600) of survey patients and only 33 had VL ≥ 1000 copies/mL, resulting in a viral suppression level of 94.48% (565/598, 95% CI 92.34-96.17%). For 23 samples, protease and reverse transcriptase (RT) genotyping were successful, with 13 sequences containing RT inhibitor surveillance drug resistance mutations (SDRMs) (56.5%). No SDRM against protease inhibitors were detected. Thirty samples were successfully genotyped for integrase with 3 sequences (10.08%) containing integrase strand transfer inhibitor (INSTI) SDRMs. In samples successfully genotyped in the three genetic regions, 68.18% (16/22) had a genotypic susceptibility score (GSS) ≥ 2.5 for the concurrent regimen, implying factors beyond drug resistance caused the unsuppressed viral load. For five patients, GSS indicated that HIVDR may have caused the unsuppressed viral load. All three patients with INSTI resistance mutations were highly resistant to dolutegravir and accumulated nucleoside and non-nucleoside RT inhibitor HIVDR mutations. Although in this cohort the last 95 UNAIDS target was almost achieved, HIVDR mutations, including INSTIs resistance mutations were detected in HIV-positive individuals taking ART for at least one year. We recommend the design and implementation of high-impact interventions to prevent the increase of HIVDR, failure of dolutegravir and address the non-resistance factors in the study area.

The impact of a community health worker intervention on uptake of antenatal care: a cluster-randomized pragmatic trial in Dar es Salaam.

The provision of high-quality antenatal care (ANC) is important for preventing maternal and newborn mortality and morbidity, but only around half of pregnant women in Tanzania attended four or more ANC visits in 2019. Although there is emerging evidence on the benefit of community health worker (CHW) interventions on ANC uptake, few large-scale pragmatic trials have been conducted. This pragmatic cluster-randomized trial, implemented directly through the public sector health system, assessed the impact of an intervention that trained public sector CHWs to promote the uptake of ANC. We randomized 60 administrative wards in Dar es Salaam to either a targeted CHW intervention or a standard of care. The impact of the intervention was assessed using generalized estimating equations with an independent working correlation matrix to account for clustering within wards. A total of 243 908 women were included in the analysis of our primary outcome of four or more ANC visits. The intervention significantly increased the likelihood of attending four or more ANC visits [relative risk (RR): 1.42; 95% confidence interval (CI): 1.05, 1.92] and had a modest beneficial effect on the total number of ANC visits (percent change: 7.7%; 95% CI: 0.2%, 15.5%). While slightly more women in the intervention arm attended ANC in their first trimester compared with the standard-of-care arm (19% vs 18.7%), the difference was not significant (RR: 1.02; 95% CI: 0.84, 1.22). Our findings suggest that trained CHWs can increase attendance of ANC visits in Dar es Salaam and similar settings. However, additional interventions appear necessary to promote the early initiation of ANC. This study demonstrates that routine health system data can be leveraged for outcome assessment in trials and programme evaluation and that the results are likely superior, both in terms of bias and precision, to data that are collected specifically for science.

Vertical HIV transmission within 18 months post partum among women on lifelong antiretroviral therapy for HIV in Dar es Salaam, Tanzania: a prospective cohort study.

BACKGROUND: The UNAIDS estimate of vertical HIV transmission in Tanzania is high (11%), despite 84% uptake of antiretroviral therapy (ART) among pregnant women with HIV. We aimed to evaluate vertical transmission and its determinants by 18 months post partum among women on lifelong ART in routine health-care settings in Tanzania. METHODS: We conducted a prospective cohort study in 226 health facitilies across Dar-es-Salaam, Tanzania. Eligible participants were pregnant women of any age with HIV, and later their infants, who enrolled in routine health-care services for the prevention of vertical transmission. We prospectively followed up mother-infant pairs at routine monthly visits until 18 months post partum and extracted data from the care and treatment clinic (CTC2) database, a national electronic database that stores patient-level HIV care and treatment clinic data. The primary outcome was time from birth to HIV diagnosis, defined as a positive infant HIV DNA PCR or antibody test from age 18 months. We used the Kaplan-Meier method to estimate cumulative risk of vertical transmission by 18 months post partum and Cox proportional hazards regression with shared frailties to account for potential clustering in health facilities to evaluate predictors of transmission. FINDINGS: Between Jan 1, 2015, and Dec 31, 2017, 22 930 pregnant women with HIV (median age 30 years, IQR 25-34) enrolled on a care programme. After excluding 9140 (39·9%) women and 539 (2·4%) infants with missing outcome data, 13 251 (59·0%) mother-infant pairs were analysed, of whom 6072 (45·8%) women were already on ART before pregnancy. By 18 months post partum, 159 (1·2%) of 13 251 infants were diagnosed with HIV, equivalent to a risk of vertical transmission of 1·4% (95% CI 1·2-1·6). In the complete case analysis, the rates of vertical transmission were higher among women who enrolled in the third trimester of pregnancy than among those who enrolled in the first trimester (adjusted hazard ratio 3·01, 95% CI 1·59-5·70; p=0·0003), among women with advanced HIV disease than among those with early-stage disease (1·89, 1·22-2·93; p=0·0046), and among women who were on a second-line ART regimen than among those on a first-line regimen (3·58, 1·08-11·82; p=0·037). By contrast, the rate of vertical transmission was lower among women who were already on ART at enrolment than among those starting ART at enrolment (0·39, 0·25-0·60; p<0·0001) as well as among women in high-volume clinics than among those in low-volume clinics (0·46 (0·24-0·90; p<0·0097). INTERPRETATION: Provision of ART for life (WHO's option B+ recommendation) has reduced the risk of vertical transmission to less than 2% among pregnant women with HIV in routine care settings in urban Tanzania. There is still a need to improve timely HIV diagnosis and ART uptake, and to optimise follow-up for the prevention of vertical transmission and the uptake of infant HIV testing. FUNDING: Swedish International Development Cooperation Agency.

Re-evaluating the health impact and cost-effectiveness of tuberculosis preventive treatment for modern HIV cohorts on antiretroviral therapy: a modelling analysis using data from Tanzania.

BACKGROUND: Isoniazid preventive therapy (IPT) can prevent tuberculosis among people receiving antiretroviral therapy (ART). HIV programmes are now initiating patients on ART with higher average CD4 cell counts and lower tuberculosis risks under test-and-treat guidelines. We aimed to investigate how this change has affected the health impact and cost-effectiveness of IPT. METHODS: We constructed a tuberculosis-HIV microsimulation model parameterised using data from a large HIV treatment programme in Dar es Salaam, Tanzania. We simulated long-term health and cost outcomes for the 211 748 individuals initiating ART between Jan 1, 2014, and Dec 31, 2020, under three scenarios: no IPT access; observed levels of IPT access (75%) and completion (71%); and full (100%) IPT access and completion. We stratified results by ART initiation year and starting CD4 cell count. FINDINGS: Observed levels of IPT access were estimated to have averted 12 800 (95% uncertainty interval 7300 to 21 600) disability-adjusted life-years (DALYs) and saved US$23 000 (-2 268 000 to 1 388 000). Full IPT access would have averted 24 500 (15 100 to 38 300) DALYs and cost $825 000 (-1 594 000 to 4 751 000), equivalent to $23·4 per DALY averted. Lifetime health benefits of IPT were estimated to be greater for more recent ART cohorts, while lifetime costs were stable. In subgroup analyses, a higher CD4 cell count at ART initiation was associated with greater health gains from IPT (15 900 [10 300 to 22 500] DALYs averted by full IPT per 100 000 patients for CD4 count >500 cells per µL at ART initiation, versus 7400 [4500 to 11 600] for CD4 count <100 cells per µL) and lower incremental lifetime costs. INTERPRETATION: IPT remains highly cost-effective or cost-saving for recent ART cohorts. The health impact and cost-effectiveness of IPT are estimated to improve as patients initiate ART earlier in the course of infection. FUNDING: US National Institutes of Health.

Effect of peer-mother interactive programme on prevention of mother-to-child HIV transmission outcomes among pregnant women on anti-retroviral treatment in routine healthcare in Dar es Salaam, Tanzania.

Peer support services are increasingly being integrated in programmes for the prevention of mother-to-child HIV transmission (PMTCT). We aimed to evaluate the effect of a peer-mother interactive programme on PMTCT outcomes among pregnant women on anti-retroviral treatment (ART) in routine healthcare in Dar es Salaam, Tanzania. Twenty-three health facilities were cluster-randomized to a peer-mother intervention and 24 to a control arm. We trained 92 ART experienced women with HIV to offer peer education, adherence and psychosocial support to women enrolling in PMTCT care at the intervention facilities. All pregnant women who enrolled in PMTCT care at the 47 facilities from 1st January 2018 to 31st December 2019 were identified and followed up to 31st July 2021. The primary outcome was time to ART attrition (no show >90 days since the scheduled appointment, excluding transfers) and any difference in one-year retention in PMTCT and ART care between intervention and control facilities. Secondary outcomes were maternal viral suppression (<400 viral copies/mL) and mother-to-child HIV transmission (MTCT) by ≥12 months post-partum. Analyses were done using Kaplan Meier and Cox regression (ART retention/attrition), generalized estimating equations (viral suppression) and random effects logistic regression (MTCT); reporting rates, proportions and 95% confidence intervals (CI). There were 1957 women in the peer-mother and 1384 in the control facilities who enrolled in routine PMTCT care during 2018-2019 and were followed for a median [interquartile range (IQR)] of 23 [10, 31] months. Women in both groups had similar median age of 30 [IQR 25, 35] years, but differed slightly with regard to proportions in the third pregnancy trimester (14% versus 19%); advanced HIV (22% versus 27%); and ART naïve (55% versus 47%). Peer-mother facilities had a significantly lower attrition rate per 1000 person months (95%CI) of 14 (13, 16) versus 18 (16, 19) and significantly higher one-year ART retention (95%CI) of 78% (76, 80) versus 74% (71, 76) in un-adjusted analyses, however in adjusted analyses the effect size was not statistically significant [adjusted hazard ratio of attrition (95%CI) = 0.85 (0.67, 1.08)]. Viral suppression (95%CI) was similar in both groups [92% (91, 93) versus 91% (90, 92)], but significantly higher among ART naïve women in peer-mother [91% (89, 92)] versus control [88% (86, 90)] facilities. MTCT (95%CI) was similar in both groups [2.2% (1.4, 3.4) versus 1.5% (0.7, 2.8)]. In conclusion, we learned that integration of peer-mother services in routine PMTCT care improved ART retention among all women and viral suppression among ART naïve women but had no significant influence on MTCT.

Willingness to pay for community delivery of antiretroviral treatment in urban Tanzania: a cross-sectional survey.

Community health worker (CHW)-led community delivery of HIV antiretroviral therapy (ART) could increase ART coverage and decongest healthcare facilities. It is unknown how much patients would be willing to pay to receive ART at home and, thus, whether ART community delivery could be self-financing. Set in Dar es Salaam, this study aimed to determine patients' willingness to pay (WTP) for CHW-led ART community delivery. We sampled ART patients living in the neighbourhoods surrounding each of 48 public-sector healthcare facilities in Dar es Salaam. We asked participants (N = 1799) whether they (1) preferred ART community delivery over standard facility-based care, (2) would be willing to pay for ART community delivery and (3) would be willing to pay each of an incrementally increasing range of prices for the service. 45.0% (810/1799; 95% CI: 42.7-47.3) of participants preferred ART community delivery over standard facility-based care and 51.5% (417/810; 95% CI: 48.1-55.0) of these respondents were willing to pay for ART community delivery. Among those willing to pay, the mean and median amount that participants were willing to pay for one ART community delivery that provides a 2-months' supply of antiretroviral drugs was 3.61 purchasing-power-parity-adjusted dollars (PPP$) (95% CI: 2.96-4.26) and 1.27 PPP$ (IQR: 1.27-2.12), respectively. An important limitation of this study is that participants all resided in neighbourhoods within the catchment area of the healthcare facility at which they were interviewed and, thus, may incur less costs to attend standard facility-based ART care than other ART patients in Dar es Salaam. While there appears to be a substantial WTP, patient payments would only constitute a minority of the costs of implementing ART community delivery. Thus, major co-financing from governments or donors would likely be required.

Cost-effectiveness analysis of integrating screening and treatment of selected non-communicable diseases into HIV/AIDS treatment in Uganda.

INTRODUCTION: Despite growing enthusiasm for integrating treatment of non-communicable diseases (NCDs) into human immunodeficiency virus (HIV) care and treatment services in sub-Saharan Africa, there is little evidence on the potential health and financial consequences of such integration. We aim to study the cost-effectiveness of basic NCD-HIV integration in a Ugandan setting. METHODS: We developed an epidemiologic-cost model to analyze, from the provider perspective, the cost-effectiveness of integrating hypertension, diabetes mellitus (DM) and high cholesterol screening and treatment for people living with HIV (PLWH) receiving antiretroviral therapy (ART) in Uganda. We utilized cardiovascular disease (CVD) risk estimations drawing from the previously established Globorisk model and systematic reviews; HIV and NCD risk factor prevalence from the World Health Organization's STEPwise approach to Surveillance survey and global databases; and cost data from national drug price lists, expert consultation and the literature. Averted CVD cases and corresponding disability-adjusted life years were estimated over 10 subsequent years along with incremental cost-effectiveness of the integration. RESULTS: Integrating services for hypertension, DM, and high cholesterol among ART patients in Uganda was associated with a mean decrease of the 10-year risk of a CVD event: from 8.2 to 6.6% in older PLWH women (absolute risk reduction of 1.6%), and from 10.7 to 9.5% in older PLWH men (absolute risk reduction of 1.2%), respectively. Integration would yield estimated net costs between $1,400 and $3,250 per disability-adjusted life year averted among older ART patients. CONCLUSIONS: Providing services for hypertension, DM and high cholesterol for Ugandan ART patients would reduce the overall CVD risk among these patients; it would amount to about 2.4% of national HIV/AIDS expenditure, and would present a cost-effectiveness comparable to other standalone interventions to address NCDs in low- and middle-income country settings.

Integrating care for non-communicable diseases into routine HIV services: key considerations for policy design in sub-Saharan Africa.

INTRODUCTION: There is great interest for integrating care for non-communicable diseases (NCDs) into routine HIV services in sub-Saharan Africa (SSA) due to the steady rise of the number of people who are ageing with HIV. Suggested health system approaches for intervening on these comorbidities have mostly been normative, with little actionable guidance on implementation, and on the practical, economic and ethical considerations of favouring people living with HIV (PLHIV) versus targeting the general population. We summarize opportunities and challenges related to leveraging HIV treatment platforms to address NCDs among PLHIV. We emphasize key considerations that can guide integrated care in SSA and point to possible interventions for implementation. DISCUSSION: Integrating care offers an opportunity for effective delivery of NCD services to PLHIV, but may be viewed to unfairly ignore the larger number of NCD cases in the general population. Integration can also help maintain the substantial health and economic benefits that have been achieved by the global HIV/AIDS response. Implementing interventions for integrated care will require assessing the prevalence of common NCDs among PLHIV, which can be achieved via increased screening during routine HIV care. Successful integration will also necessitate earmarking funds for NCD interventions in national budgets. CONCLUSIONS: An expanded agenda for addressing HIV-NCD comorbidities in SSA may require adding selected NCDs to conditions that are routinely monitored in PLHIV. Attention should be given to mitigating potential tradeoffs in the quality of HIV services that may result from the extra responsibilities borne by HIV health workers. Integrated care will more likely be effective in the context of concurrent health system reforms that address NCDs in the general population, and with synergies with other HIV investments that have been used to strengthen health systems.

Risk Factors for Alanine Aminotransferase Elevations in a Prospective Cohort of HIV-Infected Tanzanian Adults Initiating Antiretroviral Therapy.

INTRODUCTION: Serum alanine aminotransferase (ALT) elevations are common among HIV-infected patients on combination antiretroviral therapy (cART). APPROACH: We conducted a prospective cohort study of 3023 HIV-infected Tanzanian adults initiating cART. We assessed risk factors for mild/moderate ALT elevations >40 IU/L and severe ALT elevations >200 IU/L. RESULTS: We found that over a median follow-up of 32.5 months (interquartile range: 19.4-41.5), 44.8% of participants had at least 1 incident ALT elevation >40 IU/L of which 50.1% were persistent elevations. Risk factors for incident ALT elevation >40 IU/L included male sex, CD4 count <100 cells/µL, d4T+3TC+NVP cART, and triglycerides ≥150 mg/dL (P values <.05). Hepatitis B coinfection and alcohol consumption increased the risk of severe ALT elevations >200 IU/L (P values: <.05). CONCLUSION: Incident mild and moderate ALT elevations are common among Tanzanians initiating cART, and the clinical and demographic information can identify patients at increased risk.