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.

Adherence to Antiretroviral Therapy by Medication Possession Ratio and Virological Suppression among Adolescents and Young Adults Living with HIV in Dar es Salaam, Tanzania.

Background: Adherence to antiretroviral therapy (ART) is a strong determinant of virological suppression. We aimed to determine the magnitude of adherence as measured by medication possession ratio (MPR) and virological suppression with its predictors among adolescents and young adults (AYA) living with HIV on ART in Tanzania. Methods: This retrospective cohort study was conducted using archived data from HIV care and treatment centers in Dar es Salaam, Tanzania between 2015 and 2019. The logistic regression model assessed predictors for adherence and virological suppression. Results: Data of 5750 AYA living with HIV were analysed. The majority were females: 4748 (82.6%). About 63% had good adherence with MPR ≥ 85% at one year post ART initiation. Independent predictors of ART adherence were male sex (aOR = 1.3, 95% CI 1.1−1.5), CD4 > 500 cells/mm3 (aOR = 0.7, 95% CI: 0.6−0.9), WHO stage III (aOR = 1.6, 95% CI 1.3−1.9), enrollment in 2019 (aOR = 1.5, 95% CI 1.2−1.9), and virological suppression (aOR = 2.0, 95% CI 1.6−2.9). Using an Efavirenz- and a Nevirapine-based combination was associated with reduced odds of ART adherence (aOR = 0.3, 95% CI 0.1−0.8) and (aOR = 0.2, 95% CI 0.1−0.6), respectively. Predictors of virological suppression were MPR ≥ 85% (aOR = 2.0, 95% CI 1.6−2.4); CD4 > 500 cells/mm3 (aOR = 2.4, 95% CI 1.7−3.4), and once-daily dosing (aOR = 2.0, 95% CI 1.3−2.5). Conclusion: Adherence to ART among AYA living with HIV is suboptimal. Sex, year of enrollment, ART drug combination used, and immunological status at ART initiation are important predictors of adherence to ART and virological suppression.

Predictors of mortality among adolescents and young adults living with HIV on antiretroviral therapy in Dar es Salaam, Tanzania: a retrospective cohort study.

INTRODUCTION: Global AIDS-related deaths have declined by only 10% among adolescents since its peak in 2003. This is disproportionately low compared to a decline of 74% among children aged 0-9 years old. We determined the magnitude of, and predictors of mortality among adolescents and young adults living with HIV on antiretroviral therapy (ART) in Dar-es-Salaam, Tanzania. METHODS: A retrospective cohort study was conducted among adolescents (aged 10-19) and young adults (aged 20-24) living with HIV and enrolled in care and treatment centres in Dar es Salaam, Tanzania between January 2015 and December 2019. Data were analysed using STATA version 16. Cumulative hazard curves were used to estimate and illustrate 1-year mortality. Predictors for mortality were assessed by the Fine and Gray competing risk regression model. Sub-hazard ratios (SHR) and 95% confidence intervals (95% CI) were then reported. RESULTS: A total of 15,874 young people living with HIV were included: 4916 (31.3%) were adolescents and 10,913 (68.7%) were young adults. A total of 3843 (77.5%) adolescents and 9517 (87.2%) young adults were female. Deaths occurred in 2.3% (114/4961) of adolescents and 1.2% (135/10,913) of young adults (p < 0.001). Over a follow-up of 9292 person-years, the mortality rate was 3.8 per 100 person years [95% CI 3.2-4.6/100 person-years] among adolescents and 2.1 per 100 person-years among young adults [95% CI 1.8-2.5/100 person-years]. Independent predictors of mortality among adolescents were male sex (adjusted (SHR) aSHR = 1.90, 95% CI: 1.3-2.8), CD4 count < 200 cells/mm3 (aSHR = 2.7, 95% CI: 1.4-5.0) and attending a private health facility (aSHR = 1.7, 95% CI: 1.1-2.5). Predictors of mortality among young adults were CD4 count < 200 cells/mm3 (aSHR = 2.8, 95% CI 1.7-4.5), being underweight (aSHR = 2.1, 95% CI: 1.4-3.3) and using nevirapine-based therapy (aHR = 8.3, 95% CI: 3.5-19.5). CONCLUSIONS: The mortality rate for persons living with HIV and on ART in Tanzania was significantly higher in adolescents than young adults. Age- and sex-specific risk factors identify targets for intervention to reduce mortality among affected adolescents and young adults.

Long-term virological outcomes in women who started option B+ care during pregnancy for prevention of mother-to-child transmission of HIV in Dar es Salaam, Tanzania: a cohort study.

BACKGROUND: Option B+ marked a milestone in prevention of mother-to-child transmission (PMTCT) of HIV by recommending lifelong antiretroviral therapy (ART) for all pregnant women with HIV. Nevertheless, concerns remain regarding long-term outcomes in settings with a high HIV burden. We analysed long-term virological outcomes in women enrolled on option B+ in Tanzania. METHODS: In this prospective cohort study, we extracted data for pregnant women with HIV starting PMTCT care between Oct 1, 2014, and Sept 30, 2016, in routine health-care settings in Dar es Salaam, Tanzania, from national HIV and district health information system databases. We then excluded women who exited study sites before 6 months of ART follow-up and women who did not have a viral load test. Women were followed up until March 8, 2019. We used Poisson generalised estimating equations to examine trends in HIV viral suppression (<400 copies per mL) and virological failure (≥400 copies per mL), reporting relative risks (RRs) and 95% CIs adjusted for maternal age, gestational age, and several clinical characteristics. FINDINGS: We identified 15 586 pregnant women with HIV, of whom 10 161 were eligible for follow-up. Women were followed up for a median of 37 months (IQR 31-45) and a maximum of 53 months. The median age at PMTCT initiation was 31 years (IQR 27-35). At PMTCT enrolment, 1245 (17·0%) of 7318 women with available data were in their third trimester, 4901 (48·2%) of 10 161 women started ART at least 1 month before PMTCT enrolment, and 3380 (33·4%) of 10 131 women with available data had advanced HIV. Overall, a viral suppression rate of 88·2% (95% CI 87·8-88·7) was observed over the entire follow-up period, ranging from 85·1% (84·3-85·9) in viral load tests done at 0-11 months to 90·6% (89·7-91·4) at 36 months or longer since PMTCT enrolment. In a complete-case analysis (ie, including patients with <30% missing data; n=7306), the risk of virological failure among women who remained in HIV care decreased over time (adjusted RR 0·87 [95% CI 0·80-0·95] at 12-23 months since PMTCT enrolment; 0·65 [0·59-0·72] at 24-35 months; and 0·63 [0·55-0·71] at ≥36 months vs at 0-11 months). Younger women (aged <20 years: 1·76 [1·40-2·23] vs aged 30-39 years) and those starting PMTCT late in pregnancy (third trimester: 1·28 [1·10-1·50] vs first trimester) or with advanced HIV (1·33 [1·16-1·51] vs without advanced HIV) had increased risk of virological failure. Women who attended an antenatal care facility where more than 50% of attendees received couples HIV testing had a decreased risk of virological failure (adjusted RR 0·81 [0·65-0·99] vs <50% having couples testing). INTERPRETATION: High rates of viral suppression among women starting option B+ who remain in HIV care are sustainable, and might increase, at least up to 53 months. This rate might be further improved by addressing challenges of adolescent mothers, late presenters, and couples HIV testing at antenatal care. FUNDING: Swedish International Development Agency.

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.

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.

Antiretroviral Therapy in Relation to Birth Outcomes among HIV-infected Women: A Cohort Study.

Although the beneficial effects of antiretroviral (ARV) therapy for preventing mother-to-child transmission are indisputable, studies in developed and developing countries have reported conflicting findings on the association between ARV exposure and adverse birth outcomes. We conducted a prospective observational study at 10 human immunodeficiency virus (HIV) care and treatment centers in Dar es Salaam, Tanzania. Multivariate log-binomial regression was used to investigate the associations between ARV use and adverse birth outcomes among HIV-negative HIV-exposed infants. Our findings demonstrate an increased risk of adverse birth outcomes associated with the use of highly active antiretroviral therapy during pregnancy. Further studies are needed to investigate the underlying mechanisms and identify the safest ARV regimens for use during pregnancy.

Time trends of baseline demographics and clinical characteristics of HIV infected children enrolled in care and treatment service in Dar es Salaam, Tanzania.

BACKGROUND: Few studies have described time-based trends of clinical and demographic characteristics of children enrolling in HIV and AIDS care and treatment services. We present findings of a study that explored time-based trends of baseline characteristics among children enrolling into 26 public HIV care facilities in Dar es Salaam, Tanzania. METHODS: Children enrolled between October 2004 and September 2011 was included in these analyses. The year of enrollment was used as the primary predictor of interest, and log linear and linear regressions model were used to analyze dichotomous and continuous variables respectively. P-values under 0.05 were considered significant. RESULTS: Among the 6,579 children enrolled, the proportion with advanced disease at enrollment increased from 35% to 58%, mean age increasing from 5.0 to 6.2 years (p < 0.0001), proportion of children less than 2 years decreased from 35% to 29%. While the median hemoglobin concentration rose from 9.1 g/dl to 10.3 g/dl (P <0.0001), proportion with a history of past TB dropped from 25% to 12.8% (P < 0.0001). Over time, health centers and dispensaries enrolled more children as compared to hospitals (P < 0.0001). Temeke district, which has the lowest socioeconomic status among the three districts in Dar es Salaam, had a significant increase in enrollment from 22% to 25% (P = 0.02). CONCLUSION: We found that as time progressed, children were enrolled in care and treatment services at an older age sicker status as evidenced by increase in mean age and more advanced disease stage at first contact with providers. We recommend more efforts be focused on scaling up early HIV infant diagnosis and enrollment to HIV care and treatment.

Community health workers to improve antenatal care and PMTCT uptake in Dar es Salaam, Tanzania: a quantitative performance evaluation.

BACKGROUND: Home visits by community health workers (CHW) could be effective in identifying pregnant women in the community before they have presented to the health system. CHW could thus improve the uptake of antenatal care (ANC), HIV testing, and prevention of mother-to-child transmission (PMTCT) services. METHODS: Over a 16-month period, we carried out a quantitative evaluation of the performance of CHW in reaching women early in pregnancy and before they have attended ANC in Dar es Salaam, Tanzania. RESULTS: As part of the intervention, 213 CHW conducted more than 45,000 home visits to about 43,000 pregnant women. More than 75% of the pregnant women identified through home visits had not yet attended ANC at the time of the first contact with a CHW and about 40% of those who had not yet attended ANC were in the first trimester of pregnancy. Over time, the number of pregnant women the CHW identified each month increased, as did the proportion of women who had not yet attended ANC. The median gestational age of pregnant women contacted for the first time by a CHW decreased steadily and significantly over time (from 21/22 to 16 weeks, P-value for test of trend <0.0001). CONCLUSIONS: A large-scale CHW intervention was effective in identifying pregnant women in their homes early in pregnancy and before they had attended ANC. The intervention thus fulfills some of the conditions that are necessary for CHW to improve timely ANC uptake and early HIV testing and PMTCT enrollment in pregnancy.

Evaluation of a community health worker intervention and the World Health Organization's Option B versus Option A to improve antenatal care and PMTCT outcomes in Dar es Salaam, Tanzania: study protocol for a cluster-randomized controlled health systems implementation trial.

BACKGROUND: Mother-to-child transmission of HIV remains an important public health problem in sub-Saharan Africa. As HIV testing and linkage to PMTCT occurs in antenatal care (ANC), major challenges for any PMTCT option in developing countries, including Tanzania, are delays in the first ANC visit and a low overall number of visits. Community health workers (CHWs) have been effective in various settings in increasing the uptake of clinical services and improving treatment retention and adherence. At the beginning of this trial in January 2013, the World Health Organization recommended either of two medication regimens, Option A or B, for prevention of mother-to-child transmission of HIV (PMTCT). It is still largely unclear which option is more effective when implemented in a public healthcare system. This study aims to determine the effectiveness, cost-effectiveness, acceptability, and feasibility of: (1) a community health worker (CWH) intervention and (2) PMTCT Option B in improving ANC and PMTCT outcomes. METHODS/DESIGN: This study is a cluster-randomized controlled health systems implementation trial with a two-by-two factorial design. All 60 administrative wards in the Kinondoni and Ilala districts in Dar es Salaam were first randomly allocated to either receiving the CHW intervention or not, and then to receiving either Option B or A. Under the standard of care, facility-based health workers follow up on patients who have missed scheduled appointments for PMTCT, first through a telephone call and then with a home visit. In the wards receiving the CHW intervention, the CHWs: (1) identify pregnant women through home visits and refer them to antenatal care; (2) provide education to pregnant women on antenatal care, PMTCT, birth, and postnatal care; (3) routinely follow up on all pregnant women to ascertain whether they have attended ANC; and (4) follow up on women who have missed ANC or PMTCT appointments. TRIAL REGISTRATION: ClinicalTrials.gov: EJF22802. Registration date: 14 May 2013.