Rudi Kundini, Pamoja Kundini (RKPK): study protocol for a hybrid type 1 randomized effectiveness-implementation trial using data science and economic incentive strategies to strengthen the continuity of care among people living with HIV in Tanzania.

BACKGROUND: Economic incentives can improve clinical outcomes among in-care people living with HIV (PLHIV), but evidence is limited for their effectiveness among out-of-care PLHIV or those at risk of disengagement. We propose a type 1 hybrid effectiveness-implementation study to advance global knowledge about the use of economic incentives to strengthen the continuity of HIV care and accelerate global goals for HIV epidemic control. METHODS: The Rudi Kundini, Pamoja Kundini study will evaluate two implementation models of an economic incentive strategy for supporting two groups of PLHIV in Tanzania. Phase 1 of the study consists of a two-arm, cluster randomized trial across 32 health facilities to assess the effectiveness of a home visit plus one-time economic incentive on the proportion of out-of-care PLHIV with viral load suppression (< 1000 copies/ml) 6 months after enrollment (n = 640). Phase 2 is an individual 1:1 randomized controlled trial designed to determine the effectiveness of a short-term counseling and economic incentive program offered to in-care PLHIV who are predicted through machine learning to be at risk of disengaging from care on the outcome of viral load suppression at 12 months (n = 692). The program includes up to three incentives conditional upon visit attendance coupled with adapted counselling sessions for this population of PLHIV. Consistent with a hybrid effectiveness-implementation study design, phase 3 is a mixed methods evaluation to explore barriers and facilitators to strategy implementation in phases 1 and 2. Results will be used to guide optimization and scale-up of the incentive strategies, if effective, to the larger population of Tanzanian PLHIV who struggle with continuity of HIV care. DISCUSSION: Innovative strategies that recognize the dynamic process of lifelong retention in HIV care are urgently needed. Strategies such as conditional economic incentives are a simple and effective method for improving many health outcomes, including those on the HIV continuum. If coupled with other supportive services such as home visits (phase 1) or with tailored counselling (phase 2), economic incentives have the potential to strengthen engagement among the subpopulation of PLHIV who struggle with retention in care and could help to close the gap towards reaching global "95-95-95" goals for ending the AIDS epidemic. TRIAL REGISTRATION: Phase 1: ClinicalTrials.gov, NCT05248100 , registered 2/21/2022. Phase 2: ClinicalTrials.gov, NCT05373095 , registered 5/13/2022.

Removal of long-acting reversible contraceptive methods and quality of care in Dar es Salaam, Tanzania: Client and provider perspectives from a secondary analysis of cross-sectional survey data from a randomized controlled trial.

Access to removal of long-acting reversible contraception (LARCs) (e.g., implants and intrauterine devices (IUDs)) is an essential part of contraceptive care. We conducted a secondary analysis of cross-sectional survey data from a randomized controlled trial. We analyzed 5,930 client surveys and 259 provider surveys from 73 public sector facilities in Tanzania to examine the receipt of desired LARC removal services among clients and the association between receipt of desired LARC removal and person-centered care. We used provider survey data to contextualize these findings, describing provider attitudes and training related to LARC removals. All facilities took part in a larger randomized controlled trial to assess the Beyond Bias intervention, a provider-focused intervention to reduce provider bias on the basis of age, marital status, and parity. Thirteen percent of clients did not receive a desired LARC removal during their visit. Clients who were young, had lower perceived socioeconomic status, and visited facilities that did not take part in the Beyond Bias intervention were less likely to receive a desired removal. Clients who received a desired LARC removal reported higher levels of person-centered care (ß = .07, CI: .02 - .11, p = < .01). Half of providers reported not being comfortable removing a LARC before its expiration (51%) or if they disagreed with the client's decision (49%). Attention is needed to ensure clients can get their LARCs removed when they want to ensure patient-centered care and protect client autonomy and rights. Interventions like the Beyond Bias intervention, may work to address provider-imposed barriers to LARC removals.

Incidence and determinants of adverse events in individuals with HIV commencing Dolutegravir-based antiretroviral therapy in mainland Tanzania.

Tanzania adopted a Dolutegravir (DTG)-based regimen as first-line treatment in 2019 following the World Health Organization recommendation. Data on the DTG safety profile from sub-Saharan Africa including Tanzania are limited. We investigated the incidence of DTG-related adverse events (AEs) and associated factors among people living with HIV (PLHIV) initiated on a DTG regimen. A prospective cohort study was conducted from 25 Care and Treatment Clinics in mainland Tanzania. PLHIV aged 12 years and above who were initiated on a DTG-based regimen were actively followed up for three months. The Cox regression model was used to determine the predictors of occurrence of AEs over time. A p-value of 0.05 was considered statistically significant. From January 2020 to June 2022, a cohort of 935 participants who were both newly diagnosed and ART-experienced who transitioned to a DTG-based regimen was enrolled. Out of 935 participants, 59 (6.3%) reported a total of 62 AEs. The most frequently experienced AE was skin itching and rashes (15/62; 24.2%). DTG-associated neuropsychiatric AEs were less common and included headache (6 [9.6%]) and sleep disturbances (3 [4.8%]). The overall incidence of occurrence of the first AEs was 96.7 per 1000 person-months [95% C.I: 74.4-125.7] with the highest incidence observed among the elderly (≥ 60 years). Individuals on WHO HIV Clinical Stage 2 had a 2.7 significantly higher risk of developing AEs (adjusted hazard ratio = 2.73, 95% CI = 1.46-5.12, p = 0.017). We report a low incidence of grade I (mild) and grade II (moderate) DTG-associated AEs suggesting that the regimen is generally safe in the population. Continued monitoring of DTG safety in the population is recommended.

The impact of cash incentives on mental health among adults initiating antiretroviral therapy in Tanzania.

Mental illness is prevalent among people living with HIV (PLHIV) and hinders engagement in HIV care. While financial incentives are effective at improving mental health and retention in care, the specific effect of such incentives on the mental health of PLHIV lacks quantifiable evidence. We evaluated the impact of a three-arm randomized controlled trial of a financial incentive program on the mental health of adult antiretroviral therapy (ART) initiates in Tanzania. Participants were randomized 1:1:1 into one of two cash incentive (combined; provided monthly conditional on clinic attendance) or the control arm. We measured the prevalence of emotional distress, depression, and anxiety via a difference-in-differences model which quantifies changes in the outcomes by arm over time. Baseline prevalence of emotional distress, depression, and anxiety among the 530 participants (346 intervention, 184 control) was 23.8%, 26.6%, and 19.8%, respectively. The prevalence of these outcomes decreased substantially over the study period; additional benefit of the cash incentives was not detected. In conclusion, poor mental health was common although the prevalence declined rapidly during the first six months on ART. The cash incentives did not increase these improvements, however they may have indirect benefit by motivating early linkage to and retention in care.Clinical Trial Number: NCT03341556.

HIV burden and the global fast-track targets progress among pregnant women in Tanzania calls for intensified case finding: Analysis of 2020 antenatal clinics HIV sentinel site surveillance.

BACKGROUND: For successful HIV response, updated information on the burden and progress toward HIV elimination targets are required to guide programmatic interventions. We used data from the 2020 HIV sentinel surveillance to update on the burden and factors associated with HIV infection, HIV status awareness, and ART coverage among pregnant women in Tanzania mainland. METHODOLOGY: We conducted the surveillance in 159 antenatal clinics (ANC) from all 26 regions of Tanzania's mainland from September to December 2020. This cross-sectional study included all pregnant women (≥15 years) on their first ANC visit in the current pregnancy during the survey period. Routine HIV counselling and testing were done at the facility. A multivariable logistic regression model accounting for the survey design was used to examine factors associated with HIV infections. RESULTS: 38,783 pregnant women were enrolled (median age (IQR) = 25 (21-30) years). HIV prevalence was 5.9% (95%CI: 5.3% - 6.6%), ranging from 1.9% in the Manyara region to 16.4% in the Njombe region. Older age, lower and no education, not being in a marital union, and living in urban or semi-urban areas were associated with higher odds of HIV infection. HIV status awareness among women who tested positive was 70.9% (95% CI: 67.5%- 74.0%). ART coverage among those aware of their status was 91.6% (86.5%- 94.9%). Overall, 66.6% (95% CI: 62.4%- 70.6%) of all pregnant women who tested positive for HIV knew their HIV status and were on ART. CONCLUSION: HIV is increasingly prevalent among pregnant women in Tanzania mainland especially among older, those with lower or no formal education, those outside marital union, and pregnant women living in urban and semi-urban areas. Behind the global fast-target to end HIV/ AIDS, about a third of pregnant women living with HIV initiating ANC were not on ART. Interventions to increase HIV testing and linkage to care among women of reproductive age should be intensified.

Epidemiology of syphilis infections among pregnant women in Tanzania: Analysis of the 2020 national representative sentinel surveillance.

BACKGROUND: Syphilis has detrimental effects on the health of the mother and that of both fetuses and newborns exposed in utero or at delivery. Understanding its local epidemiology is essential for policies, planning, and implementation of targeted preventive interventions. Using data from the 2020 National Sentinel Surveillance of pregnant women attending antenatal clinics (ANCs) in Tanzania we determined the prevalence and determinants of syphilis among pregnant women in Tanzania mainland. METHODOLOGY: The ANC surveillance was conducted in 159 ANC sites from all 26 regions of Tanzania's mainland from September to December 2020. It included all pregnant women 15 years and above on their first ANC visit in the current pregnancy during the survey period. Counseling for syphilis was done using standard guidelines at the ANC and testing was done using rapid SD Bioline HIV/Syphilis Duo test kits. Analysis was done using both descriptive statistics to determine the prevalence and characteristics of syphilis, whereas, logistic regressions were used to examine the independent association between syphilis and dependent variables. RESULTS: A total of 38,783 women [median age (Interquartile range (IQR)) = 25 (21-30) years] participated in the surveillance. Of them, 582 (1.4%) tested positive for syphilis. A wide regional variation was observed with the highest burden in Kagera (4.5%) to the lowest burden in Kigoma (0.3%). The odds of syphilis infections were higher among older women and those with no formal education. Compared with primigravids, women with 1-2, those with 3-4 and those with more than four previous pregnancies had 1.8 (aOR = 1.8, 95% CI: 1.2-2.5), 2.1 (aOR = 2.1, 95% CI: 1.4-3.1) and 2.6 (aOR = 2.6, 95% CI: 1.7-3.9) higher odds of syphilis infection respectively. CONCLUSION: Syphilis is still prevalent among pregnant women in Tanzania with a wide regional disparity. Efforts to prevent new infections, screen pregnant women, and treat those infected should be strategized to include all regions and renewed emphasis on regions with high burden, and importantly among women who are multipara, with a low level of education, and advanced age.

Increased prevalence of depression and anxiety among adults initiating antiretroviral therapy during the COVID-19 pandemic in Shinyanga region, Tanzania.

BACKGROUND: Concerns about the interconnected relationship between HIV and mental health were heightened during the COVID-19 pandemic. This study assessed whether there were temporal changes in the mental health status of people living with HIV presenting for care in Shinyanga region, Tanzania. Specifically, we compared the prevalence of depression and anxiety before and during COVID-19, with the goal of describing the changing needs, if any, to person-centered HIV services. METHODS: We analyzed baseline data from two randomized controlled trials of adults initiating ART in Shinyanga region, Tanzania between April-December 2018 (pre-COVID-19 period, n = 530) and May 2021-March 2022 (COVID-19 period, n = 542), respectively. We compared three mental health indicators that were similarly measured in both surveys: loss of interest in things, hopelessness about the future, and uncontrolled worrying. We also examined depression and anxiety which were measured using the Hopkins Symptom Checklist-25 in the pre-COVID-19 period and the Patient Health Questionnaire-4 in the COVID-19 period, respectively, and classified as binary indicators per each scale's threshold. We estimated prevalence differences (PD) in adverse mental health status before and during the COVID-19 pandemic, using stabilized inverse probability of treatment weighting to adjust for underlying differences in the two study populations. RESULTS: We found significant temporal increases in the prevalence of feeling 'a lot' and 'extreme' loss of interest in things ['a lot' PD: 38, CI 34,41; 'extreme' PD: 9, CI 8,12)], hopelessness about the future [' a lot' PD: 46, CI 43,49; 'extreme' PD: 4, CI 3,6], and uncontrolled worrying [' a lot' PD: 34, CI 31,37; 'extreme' PD: 2, CI 0,4] during the COVID-19 pandemic. We also found substantially higher prevalence of depression [PD: 38, CI 34,42] and anxiety [PD: 41, CI 37,45]. CONCLUSIONS: After applying a quasi-experimental weighting approach, the prevalence of depression and anxiety symptoms among those starting ART during COVID-19 was much higher than before the pandemic. Although depression and anxiety were measured using different, validated scales, the concurrent increases in similarly measured mental health indicators lends confidence to these findings and warrants further research to assess the possible influence of COVID-19 on mental health among adults living with HIV. Trial Registration NCT03351556, registered November 24, 2017; NCT04201353, registered December 17, 2019.

HIV virologic response, patterns of drug resistance mutations and correlates among adolescents and young adults: A cross-sectional study in Tanzania.

BACKGROUND: The emergence of HIV drug resistance mutations (DRMs) is of significant threat to achieving viral suppression (VS) in the quest to achieve global elimination targets. We hereby report virologic outcomes and patterns of acquired DRMs and its associated factors among adolescents and young adults (AYA) from a broader HIV drug resistance surveillance conducted in Tanzania. METHODS: Data of AYA was extracted from a cross-sectional study conducted in 36 selected facilities using a two-stage cluster sampling design. Dried blood spot (DBS) samples were collected and samples with a viral load (VL) ≥1000 copies/mL underwent genotyping for the HIV-1 pol gene. Stanford HIV database algorithm predicted acquired DRMs, Fisher's exact test and multivariable logistic regression assessed factors associated with DRMs and VS, respectively. FINDINGS: We analyzed data of 578 AYA on antiretroviral therapy (ART) for 9-15 and ≥ 36 months; among them, 91.5% and 88.2% had VS (VL<1000copies/mL) at early and late time points, respectively. Genotyping of 64 participants (11.2%) who had VL ≥1000 copies/ml detected 71.9% of any DRM. Clinically relevant DRMs were K103N, M184V, M41L, T215Y/F, L210W/L, K70R, D67N, L89V/T, G118R, E138K, T66A, T97A and unexpectedly absent K65R. Participants on a protease inhibitor (PI) based regimen were twice as likely to not achieve VS compared to those on integrase strand transfer inhibitors (INSTI). The initial VL done 6 months after ART initiation of ≥1000copies/mL was the primary factor associated with detecting DRMs (p = .019). CONCLUSIONS: VS amongst AYA is lower than the third UNAIDs target. Additionally, a high prevalence of ADR and high levels of circulating clinically relevant DRMs may compromise the long-term VS in AYA. Furthermore, the first VL result of ≥1000copies/ml after ART initiation is a significant risk factor for developing DRMs. Thus, strict VL monitoring for early identification of treatment failure and genotypic testing during any ART switch is recommended to improve treatment outcomes for AYA.

Risks of Intimate Partner Violence for Women Living with HIV Receiving Cash Transfers: A Qualitative Study in Shinyanga, Tanzania.

Cash transfers are increasingly used to motivate adherence to HIV care. However, evidence on cash transfers and intimate partner violence (IPV) is mixed and little is known about their safety for women living with HIV. We conducted in-depth interviews with women living with HIV who participated in a randomized trial providing 6 months of cash transfers (~$4.5 or $11 USD) conditional on HIV clinic attendance in Shinyanga, Tanzania to assess how receiving cash affects IPV and relationship dynamics. Eligible participants were 18-49 years, received cash transfers, and in a partnership at baseline. Data were analyzed in Dedoose using a combined inductive-deductive coding approach. 25 interviews were conducted between November 2019-February 2020. Women's employment was found to be a source of household tension and violence. None of the participants reported physical or sexual IPV in relation to cash transfers, however, some women experienced controlling behaviors or emotional violence including accusations and withholding of money, particularly those who were unemployed. Cash transfers were predominantly used for small household expenses and were not viewed as being substantial enough to shift the financial dynamic or balance of power within relationships. Our findings suggest that small, short-term cash transfers do not increase physical or sexual IPV for women living with HIV however can exacerbate controlling behaviors or emotional violence. Modest incentives used as a behavioral nudge to improve health outcomes may affect women differently than employment or larger cash transfers. Nonetheless, consultations with beneficiaries should be prioritized to protect women from potential IPV risks.

Emerging integrase strand transfer inhibitor drug resistance mutations among children and adults on ART in Tanzania: findings from a national representative HIV drug resistance survey.

BACKGROUND: Despite the scale-up of ART and the rollout in Tanzania of dolutegravir, an integrase strand transfer inhibitor (INSTI), treatment success has not been fully realized. HIV drug resistance (HIVDR), including dolutegravir resistance, could be implicated in the notable suboptimal viral load (VL) suppression among HIV patients. OBJECTIVES: To determine the prevalence and patterns of acquired drug resistance mutations (DRMs) among children and adults in Tanzania. METHODS: A national cross-sectional HIVDR survey was conducted among 866 children and 1173 adults. Genotyping was done on dried blood spot and/or plasma of participants with high HIV VL (≥1000 copies/mL). HIV genes (reverse transcriptase, protease and integrase) were amplified by PCR and directly sequenced. The Stanford HIVDR Database was used for HIVDR interpretation. RESULTS: HIVDR genotyping was performed on blood samples from 137 participants (92 children and 45 adults) with VL ≥ 1000 copies/mL. The overall prevalence of HIV DRMs was 71.5%, with DRMs present in 78.3% of children and 57.8% of adults. Importantly, 5.8% of participants had INSTI DRMs including major DRMs: Q148K, E138K, G118R, G140A, T66A and R263K. NNRTI, NRTI and PI DRMs were also detected in 62.8%, 44.5% and 8% of participants, respectively. All the participants with major INSTI DRMs harboured DRMs targeting NRTI backbone drugs. CONCLUSIONS: More than 7 in 10 patients with high HIV viraemia in Tanzania have DRMs. The early emergence of dolutegravir resistance is of concern for the efficacy of the Tanzanian ART programme.

Rudi Kundini, Pamoja Kundini (RKPK): study protocol for a hybrid type 1 randomized effectiveness-implementation trial using data science and economic incentive strategies to strengthen the continuity of care among people living with HIV in Tanzania.

Background: Economic incentives can improve clinical outcomes among in-care people living with HIV (PLHIV), but evidence is limited for their effectiveness among out-of-care PLHIV or those at-risk of disengagement. We propose a type 1 hybrid effectiveness-implementation study to advance global knowledge about the use of economic incentives to strengthen the continuity of HIV care and accelerate global goals for HIV epidemic control. Methods: The Rudi Kundini, Pamoja Kundini study will evaluate two implementation models of an economic incentive strategy for supporting two groups of PLHIV in Tanzania. Phase 1 of the study consists of a two-arm, cluster randomized trial across 32 health facilities to assess the effectiveness of a home visit plus one-time economic incentive on the proportion of out-of-care PLHIV with viral load suppression (<1000 copies/ml) 6 months after enrollment (n = 640). Phase 2 is an individual 1:1 randomized controlled trial designed to determine the effectiveness of a short-term counseling and economic incentive program offered to in-care PLHIV who are predicted through machine learning to be at-risk of disengaging from care on the outcome of viral load suppression at 12 months (n = 692). The program includes up to three incentives conditional upon visit attendance coupled with adapted counselling sessions for this population of PLHIV. Consistent with a hybrid effectiveness-implementation study design, phase 3 is a mixed methods evaluation to explore barriers and facilitators to strategy implementation in phases 1 and 2. Results will be used to guide optimization and scale-up of the incentive strategies, if effective, to the larger population of Tanzanian PLHIV who struggle with continuity of HIV care. Discussion: Innovative strategies that recognize the dynamic process of lifelong retention in HIV care are urgently needed. Strategies such as conditional economic incentives are a simple and effective method for improving many health outcomes, including those on the HIV continuum. If coupled with other supportive services such as home visits (phase 1) or with tailored counselling (phase 2), economic incentives have the potential to strengthen engagement among the subpopulation of PLHIV who struggle with retention in care and could help to close the gap towards reaching global '95-95-95' goals for ending the AIDS epidemic.Phase 1: Clinicaltrials.gov, NCT05248100, registered 2/21/2022 https://clinicaltrials.gov/ct2/show/NCT05248100Phase 2: Clinicaltrials.gov, NCT05373095, registered 5/13/2022 https://clinicaltrials.gov/ct2/show/NCT05373095.

A total facility approach to reducing HIV stigma in health facilities: implementation process and lessons learned.

OBJECTIVES: To describe development and implementation of a three-stage 'total facility' approach to reducing health facility HIV stigma in Ghana and Tanzania, to facilitate replication. DESIGN: HIV stigma in healthcare settings hinders the HIV response and can occur during any interaction between client and staff, between staff, and within institutional processes and structures. Therefore, the design focuses on multiple socioecological levels within a health facility and targets all levels of staff (clinical and nonclinical). METHODS: The approach is grounded in social cognitive theory principles and interpersonal or intergroup contact theory that works to combat stigma by creating space for interpersonal interactions, fostering empathy, and building efficacy for stigma reduction through awareness, skills, and knowledge building as well as through joint action planning for changes needed in the facility environment. The approach targets actionable drivers of stigma among health facility staff: fear of HIV transmission, awareness of stigma, attitudes, and health facility environment. RESULTS: The results are the three-stage process of formative research, capacity building, and integration into facility structures and processes. Key implementation lessons learned included the importance of formative data to catalyze action and shape intervention activities, using participatory training methodologies, involving facility management throughout, having staff, and clients living with HIV facilitate trainings, involving a substantial proportion of staff, mixing staff cadres and departments in training groups, and integrating stigma-reduction into existing structures and processes. CONCLUSION: Addressing stigma in health facilities is critical and this approach offers a feasible, well accepted method of doing so.

Effect of isoniazid preventive therapy on tuberculosis incidence and associated risk factors among HIV infected adults in Tanzania: a retrospective cohort study.

BACKGROUND: Tuberculosis (TB) continues to be the leading cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals in Sub Saharan Africa including Tanzania. Provision of isoniazid preventive therapy (IPT) is one of the public health interventions to reduce the burden of TB among HIV infected persons. However there is limited information about the influence of IPT on TB incidence in Tanzania. This study aimed at ascertaining the effect of IPT on TB incidence and to determine risk factors for TB among HIV positive adults in Dar es Salaam region. METHODS: A retrospective cohort study was conducted using secondary data of HIV positive adults receiving care and treatment services in Dar es Salaam region from 2011 to 2014. TB incidence rate among HIV positive adults on IPT was compared to those who were not on IPT during the follow up period. Risk factors for incident TB were estimated using multivariate Cox proportional hazards regression model. RESULTS: A total of 68,378 HIV positive adults were studied. The median follow up time was 3.4 (IQR = 1.9-3.8) years for patients who ever received IPT and 1.3 (IQR = 0.3-1.3) years among those who never received IPT. A total of 3124 TB cases occurred during 114,926 total person-years of follow up. The overall TB incidence rate was 2.7/100 person-years (95%CI; 2.6-2.8). Patients on IPT had 48% lower TB incidence rate compared to patients who were not on IPT (IRR = 0.52, 95%CI; 0.46-0.59). Factors associated with higher risk for incident TB included; being male (aHR = 1.8, 95% CI; 1.6-2.0), WHO stage III (aHR = 2.7, 95% CI; 2.3-3.3) and IV (aHR = 2.4, 95% CI; 1.9-3.1),being underweight (aHR = 1.7, 95% CI; 1.5-1.9) while overweight (aHR = 0.7, 95% CI; 0.6-0.8), obese (aHR = 0.5, 95% CI; 0.4-0.7), having baseline CD4 cell count between 200 and 350 cells/µl (aHR = 0.7, 95% CI; 0.6-0.8) and CD4 count above 350 cells/µl (aHR = 0.5, 95% CI; 0.4-0.6) were associated with lower risk of developing TB. CONCLUSION: Isoniazid preventive therapy (IPT) has shown to be effective in reducing TB incidence among HIV infected adults in Dar es Salaam. More efforts are needed to increase the provision and coverage of IPT.