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. We sought 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.

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.

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.

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.

Anemia, Iron Deficiency, and Iron Supplementation in Relation to Mortality among HIV-Infected Patients Receiving Highly Active Antiretroviral Therapy in Tanzania.

Anemia in HIV-infected patients improves with highly active antiretroviral therapy (HAART); however, it may still be associated with mortality among patients receiving treatment. We examined the associations of anemia severity and iron deficiency anemia (IDA) at HAART initiation and during monthly prospective follow-up with mortality among 40,657 adult HIV-infected patients receiving HAART in Dar es Salaam, Tanzania. Proportional hazards models were used to examine the associations of anemia severity and IDA at HAART initiation and during follow-up with mortality. A total of 6,261 deaths were reported. Anemia severity at HAART initiation and during follow-up was associated with an increasing risk of mortality (trend tests P < 0.001). There was significantly higher mortality risk associated with IDA at HAART initiation and during follow-up versus no anemia or iron deficiency (both P < 0.001). These associations differed significantly by gender, body mass index, and iron supplement use (all interaction test P < 0.001). The magnitude of association was stronger among men. Mortality risk with severe anemia was 13 times greater versus no anemia among obese patients, whereas it was only two times greater among underweight patients. Higher mortality risk was observed among iron supplement users, irrespective of anemia severity. Anemia and IDA were significantly associated with a higher mortality risk in patients receiving HAART. Iron supplementation indicated an increased mortality risk, and its role in HIV infections should be examined in future studies. Given the low cost of assessing anemia, it can be used frequently to identify high-risk patients in resource-limited settings.

Community health workers to improve uptake of maternal healthcare services: A cluster-randomized pragmatic trial in Dar es Salaam, Tanzania.

BACKGROUND: Home delivery and late and infrequent attendance at antenatal care (ANC) are responsible for substantial avoidable maternal and pediatric morbidity and mortality in sub-Saharan Africa. This cluster-randomized trial aimed to determine the impact of a community health worker (CHW) intervention on the proportion of women who (i) visit ANC fewer than 4 times during their pregnancy and (ii) deliver at home. METHODS AND FINDINGS: As part of a 2-by-2 factorial design, we conducted a cluster-randomized trial of a home-based CHW intervention in 2 of 3 districts of Dar es Salaam from 18 June 2012 to 15 January 2014. Thirty-six wards (geographical areas) in the 2 districts were randomized to the CHW intervention, and 24 wards to the standard of care. In the standard-of-care arm, CHWs visited women enrolled in prevention of mother-to-child HIV transmission (PMTCT) care and provided information and counseling. The intervention arm included additional CHW supervision and the following additional CHW tasks, which were targeted at all pregnant women regardless of HIV status: (i) conducting home visits to identify pregnant women and refer them to ANC, (ii) counseling pregnant women on maternal health, and (iii) providing home visits to women who missed an ANC or PMTCT appointment. The primary endpoints of this trial were the proportion of pregnant women (i) not making at least 4 ANC visits and (ii) delivering at home. The outcomes were assessed through a population-based household survey at the end of the trial period. We did not collect data on adverse events. A random sample of 2,329 pregnant women and new mothers living in the study area were interviewed during home visits. At the time of the survey, the mean age of participants was 27.3 years, and 34.5% (804/2,329) were pregnant. The proportion of women who reported having attended fewer than 4 ANC visits did not differ significantly between the intervention and standard-of-care arms (59.1% versus 60.7%, respectively; risk ratio [RR]: 0.97; 95% CI: 0.82-1.15; p = 0.754). Similarly, the proportion reporting that they had attended ANC in the first trimester did not differ significantly between study arms. However, women in intervention wards were significantly less likely to report having delivered at home (3.9% versus 7.3%; RR: 0.54; 95% CI: 0.30-0.95; p = 0.034). Mixed-methods analyses of additional data collected as part of this trial suggest that an important reason for the lack of effect on ANC outcomes was the perceived high economic burden and inconvenience of attending ANC. The main limitations of this trial were that (i) the outcomes were ascertained through self-report, (ii) the study was stopped 4 months early due to a change in the standard of care in the other trial that was part of the 2-by-2 factorial design, and (iii) the sample size of the household survey was not prespecified. CONCLUSIONS: A home-based CHW intervention in urban Tanzania significantly reduced the proportion of women who reported having delivered at home, in an area that already has very high uptake of facility-based delivery. The intervention did not affect self-reported ANC attendance. Policy makers should consider piloting, evaluating, and scaling interventions to lessen the economic burden and inconvenience of ANC. TRIAL REGISTRATION: ClinicalTrials.gov NCT01932138.

The effect of a community health worker intervention on public satisfaction: evidence from an unregistered outcome in a cluster-randomized controlled trial in Dar es Salaam, Tanzania.

BACKGROUND: There is a dearth of evidence on the causal effects of different care delivery approaches on health system satisfaction. A better understanding of public satisfaction with the health system is particularly important within the context of task shifting to community health workers (CHWs). This paper determines the effects of a CHW program focused on maternal health services on public satisfaction with the health system among women who are pregnant or have recently delivered. METHODS: From January 2013 to April 2014, we carried out a cluster-randomized controlled health system implementation trial of a CHW program. Sixty wards in Dar es Salaam, Tanzania, were randomly allocated to either a maternal health CHW program (36 wards) or the standard of care (24 wards). From May to August 2014, we interviewed a random sample of women who were either currently pregnant or had recently delivered a child. We used five-level Likert scales to assess women's satisfaction with the CHW program and with the public-sector health system in Dar es Salaam. RESULTS: In total, 2329 women participated in the survey (response rate 90.2%). Households in intervention areas were 2.3 times as likely as households in control areas to have ever received a CHW visit (95% CI 1.8, 3.0). The intervention led to a 16-percentage-point increase in women reporting they were satisfied or very satisfied with the CHW program (95% CI 3, 30) and a 15-percentage-point increase in satisfaction with the public-sector health system (95% CI 3, 27). CONCLUSIONS: A CHW program for maternal and child health in Tanzania achieved better public satisfaction than the standard CHW program. Policy-makers and implementers who are involved in designing and organizing CHW programs should consider the potential positive impact of the program on public satisfaction. TRIAL REGISTRATION: ClinicalTrials.gov, EJF22802.

Effectiveness of a multivitamin supplementation program among HIV-infected adults in Tanzania.

OBJECTIVE: The objective of this study was to assess the effectiveness of a routine multivitamin supplementation program for adults living with HIV in Tanzania. DESIGN: We conducted a retrospective cohort study of 67 707 adults enrolled in the Dar es Salaam HIV care and treatment program during 2004-2012. METHODS: The Dar es Salaam HIV care and treatment program intended to provide all adult patients with multivitamin supplements (vitamins B-complex, C, and E) free of charge; however, intermittent stockouts and other implementation issues did not afford universal coverage. We use Cox proportional hazard models to assess the time-varying association of multivitamin supplementation with mortality and clinical outcomes. RESULTS: The study cohort contributed 41 540 and 129 315 person-years of follow-up time to the antiretroviral therapy (ART)-naive and ART-experienced analyses, respectively. Among 48 207 ART-naive adults, provision of multivitamins reduced the risk of mortality [adjusted hazard ratio (aHR): 0.69; 95% confidence interval (CI): 0.59-0.81], incident tuberculosis (TB) (aHR: 0.83; 0.76-0.91), and meeting ART eligibility criteria (aHR: 0.78; 95% CI: 0.73-0.83) after adjustment for time-varying confounding. Among 46 977 ART-experienced patients, multivitamins reduced mortality (hazard ratio: 0.86; 95% CI: 0.80-0.92), incident TB (aHR: 0.78; 95% CI: 0.73-0.84), and immunologic failure (aHR: 0.70; 95% CI: 0.67-0.73). The survival benefits associated with provision multivitamins appeared to be greatest during the first year of ART and declined over time (P value <0.001). CONCLUSION: Multivitamin supplementation appears to be a simple, effective, safe, and scalable program to improve survival, reduce incidence of TB, and improve treatment outcomes for adult HIV patients in Tanzania.

Community delivery of antiretroviral drugs: A non-inferiority cluster-randomized pragmatic trial in Dar es Salaam, Tanzania.

BACKGROUND: With the increase in people living with HIV in sub-Saharan Africa and expanding eligibility criteria for antiretroviral therapy (ART), there is intense interest in the use of novel delivery models that allow understaffed health systems to successfully deal with an increasing demand for antiretroviral drugs (ARVs). This pragmatic randomized controlled trial in Dar es Salaam, Tanzania, evaluated a novel model of ARV community delivery: lay health workers (home-based carers [HBCs]) deliver ARVs to the homes of patients who are clinically stable on ART, while nurses and physicians deliver standard facility-based care for patients who are clinically unstable. Specifically, the trial aimed to assess whether the ARV community delivery model performed at least equally well in averting virological failure as the standard of care (facility-based care for all ART patients). METHODS AND FINDINGS: The study took place from March 1, 2016, to October 27, 2017. All (48) healthcare facilities in Dar es Salaam that provided ART and had an affiliated team of public-sector HBCs were randomized 1:1 to either (i) ARV community delivery (intervention) or (ii) the standard of care (control). Our prespecified primary endpoint was the proportion of adult non-pregnant ART patients with virological failure at the end of the study period. The prespecified margin of non-inferiority was a risk ratio (RR) of 1.45. The mean follow-up period was 326 days. We obtained intent-to-treat (ITT) RRs using a log-binomial model adjusting standard errors for clustering at the level of the healthcare facility. A total of 2,172 patients were enrolled at intervention (1,163 patients) and control (1,009 patients) facilities. Of the 1,163 patients in the intervention arm, 516 (44.4%) were both clinically stable on ART and opted to receive ARVs in their homes or at another meeting point of their choosing in the community. At the end of the study period, 10.9% (95/872) of patients in the control arm and 9.7% (91/943) in the intervention arm were failing virologically. The ITT RR for virological failure demonstrated non-inferiority of the ARV community delivery model (RR 0.89 [1-sided 95% CI 0.00-1.18]). We observed no significant difference between study arms in self-reported patient healthcare expenditures over the last 6 months before study exit. Of those who received ARVs in the community, 97.2% (95% CI 94.7%-98.7%) reported being either "satisfied" or "very satisfied" with the program. Other than loss to follow-up (18.9% in the intervention and 13.6% in the control arm), the main limitation of this trial was that substantial decongestion of healthcare facilities was not achieved, thus making the logic for our preregistered ITT approach (which includes those ineligible to receive ARVs at home in the intervention sample) less compelling. CONCLUSIONS: In this study, an ARV community delivery model performed at least as well as the standard of care regarding the critical health indicator of virological failure. The intervention did not significantly reduce patient healthcare expenditures, but satisfaction with the program was high and it is likely to save patients time. Policy-makers should consider piloting, evaluating, and scaling more ambitious ARV community delivery programs that can reach higher proportions of ART patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02711293.

Incidence and Risk Factors for Overweight and Obesity after Initiation of Antiretroviral Therapy in Dar es Salaam, Tanzania.

OBJECTIVE: To describe the incidence of and risk factors for overweight and obesity following antiretroviral therapy (ART) initiation. METHODS: We used Cox proportional hazards models to investigate risk factors for incident overweight and obesity in 79 074 individuals aged 15 years or older who initiated ART in Dar es Salaam, Tanzania. RESULTS: Twenty-five percent of the patients became overweight and 10% became obese. The incidence rate of obesity was 3.2 per 100 person-years (95% confidence interval [CI]: 3.1-3.3) in patients who were of normal weight before starting ART and 22.6 per 100 person-years (95% CI: 21.9-23.3) in those who were overweight. Lower CD4 count was associated with a higher risk of overweight and obesity ( P value for trend < .0001). CONCLUSION: There is a high burden of overweight and obesity after starting ART, leading to proportions of these 2 conditions that are similar to those in the general population.

Equity of child and adolescent treatment, continuity of care and mortality, according to age and gender among enrollees in a large HIV programme in Tanzania.

INTRODUCTION: Global scale up of anti-retroviral therapy (ART) has led to expansion of HIV treatment and prevention across sub-Saharan Africa. However, age and gender-specific disparities persist leading to failures in fulfillment of Sustainability Development Goals, including SDG3 (achieving healthy lives and wellbeing for all, at all ages) and SDG5 (gender equality). We assessed ART initiation and adherence, loss to follow-up, all-cause death and early death, according to SDG3 and SDG5 indicators among a cohort of HIV-infected children and adolescents enrolled in care in Dar-es-Salaam, Tanzania METHODS: SDG3 indicators included young (<5 years) and older paediatric children (5 to <10 years), early adolescent (10 to <15 years) and late adolescent (15 to <20 years) age group divisions and the SDG5 indicator was gender. Associations of age group and gender with ART initiation, loss to follow-up and all-cause death, were analysed using Cox proportional hazards regression and with adherence, using generalized estimating equations (GEE) with the Poisson distribution. Associations of age group and gender with early death were analysed, using log-Poisson regression with empirical variance. RESULTS: A total of 18,315 enrollees with at least one clinic visit were included in this cohort study. Of these 7238 (40%) were young paediatric , 4169 (23%) older paediatric, 2922 (16%) early adolescent and 3986 (22%) late adolescent patients at enrolment. Just over half of paediatric and early adolescents and around four fifths of the late adolescents were female. Young paediatric patients were at greater risk of early death, being almost twice as likely to die within 90 days. Males were at greater risk of early death once initiated on ART (HR 1.35, 95% CI 1.09, 1.66)), while females in late adolescence were at greatest risk of late death (HR 2.44 [1.60, 3.74] <0.01). Late adolescents demonstrated greater non-engagement in care (RR 1.21 (95% CI 1.16, 1.26)). Among both males and females, early paediatric and late adolescent groups experienced significantly greater loss to follow-up. CONCLUSION: These findings highlight equity concerns critical to the fulfillment of SDG3 and SDG5 within services for children and adolescents living with HIV in sub-Saharan Africa. Young paediatric and late adolescent age groups were at increased risk of late diagnosis, early death, delayed treatment initiation and loss of continuity of care. Males were more likely to die earlier. Special attention to SDG3 and SDG5 disparities for children and adolescents living with HIV will be critical for fulfillment of the 2030 SDG agenda.

Impact of Antiretroviral Therapy on the Risk of Herpes Zoster among Human Immunodeficiency Virus-Infected Individuals in Tanzania.

We examined the incidence of herpes zoster (HZ) before and after the initiation of antiretroviral therapy (ART), and risk factors for HZ among human immunodeficiency virus (HIV)-infected individuals in Tanzania. A cohort study was conducted among HIV-positive individuals enrolled in HIV care and treatment clinics in Dar es Salaam, Tanzania. A Cox proportional hazard model was used to examine the effect of ART on the risk of HZ after adjusting for sociodemographics and time-varying clinical and nutritional factors. Among 72,670 HIV-positive individuals, 2,312 incident cases of HZ (3.2%) occurred during the median follow-up of 15 months (interquartile range: 3-35). The incidence rate of HZ significantly declined from 48.9 (95% confidence interval [CI] = 46.7-51.0) per 1,000 person-years before ART to 3.7 (95% CI = 3.3-4.1) per 1,000 person-years after the initiation of ART (P < 0.001). The risk of HZ declined with longer duration on ART. Low CD4 cell count, older age, female sex, district of Dar es Salaam, and year of enrollment were independently associated with the risk of HZ in the multivariate analysis. Low body mass index and anemia were not associated with the risk of HZ. The risk of HZ substantially declined after ART initiation in this large cohort of HIV-infected individuals. Earlier initiation of ART could reduce the risk of HZ and other opportunistic infections among HIV-infected individuals in sub-Saharan Africa.