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.

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.

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.

Acquired HIV drug resistance among children and adults receiving antiretroviral therapy in Tanzania: a national representative survey protocol.

INTRODUCTION: Tanzania is making an enormous effort in scaling-up of antiretroviral therapy (ART). However, people living with HIV (PLHIV) continue to succumb to the challenge of drug resistance. Evidence on drug resistance for a national survey is unavailable in Tanzania. Therefore, we sought to assess viral suppression (vs) rates and magnitude of acquired drug resistance (ADR) among PLHIV. METHODS AND ANALYSIS: A national survey will be conducted from 26 July to 29 October 2021 in 22 regions, recruiting 2160 participants. These will include adults on ART for 9-15 months and ≥48 months and children on ART for 9-15 months and ≥36 months. A standardised questionnaire will capture participants' demographic and clinical data. Plasma and dried blood spot will be prepared for viral load testing and drug resistance genotyping. Statistical analyses to determine the burden of ADR, characteristics and factors associated therewith will be done using STATA V.15. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the National Health Research Ethics Committee of Tanzania (NIMR/HQ/R.8a/Vol.IX/3432). Appropriate participant informed consent or parental consent and assent will be obtained. Dissemination will include a survey report, conference presentations, policy briefs and peer-reviewed publications.

HIV-1 Recent Infection Testing Algorithm With Antiretroviral Drug Detection to Improve Accuracy of Incidence Estimates.

BACKGROUND: HIV-1 incidence calculation currently includes recency classification by HIV-1 incidence assay and unsuppressed viral load (VL ≥ 1000 copies/mL) in a recent infection testing algorithm (RITA). However, persons with recent classification not virally suppressed and taking antiretroviral (ARV) medication may be misclassified. SETTING: We used data from 13 African household surveys to describe the impact of an ARV-adjusted RITA on HIV-1 incidence estimates. METHODS: HIV-seropositive samples were tested for recency using the HIV-1 Limiting Antigen (LAg)-Avidity enzyme immunoassay, HIV-1 viral load, ARVs used in each country, and ARV drug resistance. LAg-recent result was defined as normalized optical density values ≤1.5. We compared HIV-1 incidence estimates using 2 RITA: RITA1: LAg-recent + VL ≥ 1000 copies/mL and RITA2: RITA1 + undetectable ARV. We explored RITA2 with self-reported ARV use and with clinical history. RESULTS: Overall, 357 adult HIV-positive participants were classified as having recent infection with RITA1. RITA2 reclassified 55 (15.4%) persons with detectable ARV as having long-term infection. Those with detectable ARV were significantly more likely to be aware of their HIV-positive status (84% vs. 10%) and had higher levels of drug resistance (74% vs. 26%) than those without detectable ARV. RITA2 incidence was lower than RITA1 incidence (range, 0%-30% decrease), resulting in decreased estimated new infections from 390,000 to 341,000 across the 13 countries. Incidence estimates were similar using detectable or self-reported ARV (R2 > 0.995). CONCLUSIONS: Including ARV in RITA2 improved the accuracy of HIV-1 incidence estimates by removing participants with likely long-term HIV infection.

Unawareness of HIV Infection Among Men Aged 15-59 Years in 13 Sub-Saharan African Countries: Findings From the Population-Based HIV Impact Assessments, 2015-2019.

BACKGROUND: Identifying men living with HIV in sub-Saharan Africa (SSA) is critical to end the epidemic. We describe the underlying factors of unawareness among men aged 15-59 years who ever tested for HIV in 13 SSA countries. METHODS: Using pooled data from the nationally representative Population-based HIV Impact Assessments, we fit a log-binomial regression model to identify characteristics related to HIV positivity among HIV-positive unaware and HIV-negative men ever tested for HIV. RESULTS: A total of 114,776 men were interviewed and tested for HIV; 4.4% were HIV-positive. Of those, 33.7% were unaware of their HIV-positive status, (range: 20.2%-58.7%, in Rwanda and Cote d'Ivoire). Most unaware men reported they had ever received an HIV test (63.0%). Age, region, marital status, and education were significantly associated with HIV positivity. Men who had HIV-positive sexual partners (adjusted prevalence ratio [aPR]: 5.73; confidence interval [95% CI]: 4.13 to 7.95) or sexual partners with unknown HIV status (aPR: 2.32; 95% CI: 1.89 to 2.84) were more likely to be HIV-positive unaware, as were men who tested more than 12 months compared with HIV-negative men who tested within 12 months before the interview (aPR: 1.58; 95% CI: 1.31 to 1.91). Tuberculosis diagnosis and not being circumcised were also associated with HIV positivity. CONCLUSION: Targeting subgroups of men at risk for infection who once tested negative could improve yield of testing programs. Interventions include improving partner testing, frequency of testing, outreach and educational strategies, and availability of HIV testing where men are accessing routine health services.

Adverse events in a large-scale VMMC programme in Tanzania: findings from a case series analysis.

INTRODUCTION: Adverse events (AEs) rates in voluntary medical male circumcision (VMMC) are critical measures of service quality and safety. While these indicators are key, monitoring AEs in large-scale VMMC programmes is not without challenges. This study presents findings on AEs that occurred in eight years of providing VMMC services in three regions of Tanzania, to provide discussion both on these events and the structural issues around maintaining safety and quality in scaled-up VMMC services. METHODS: We look at trends over time, demographic characteristics, model of VMMC and type and timing of AEs for 1307 males who experienced AEs among all males circumcised in Tabora, Njombe and Iringa regions from 2009 to 2017. We analysed deidentified client data from a VMMC programme database and performed multivariable logistic regression with district clustering to determine factors associated with intraoperative and postoperative AEs among VMMC clients. RESULTS AND DISCUSSION: Among 741,146 VMMC clients, 0.18% (1307/741,146) experienced a moderate or severe AE. The intraoperative AE rate was 2.02 per 100,000 clients, and postoperative rate was 2.29 per 1000 return clients. Multivariable logistic regression showed that older age (20 to 29 years) was significantly associated with intraoperative AEs (aOR: 3.51, 95% CI: 1.17 to 10.6). There was no statistical significant difference in AE rates by surgical method. Mobile VMMC service delivery was associated with the lowest risk of experiencing postoperative AEs (aOR:0.64, 95% CI: 0.42 to 0.98). AE rates peaked in the first one to three  years of the programme and then steadily declined. CONCLUSIONS: In a programme with robust AE monitoring methodologies, AE rates reported in these three regions were very low and declined over time. While these findings support the safety of VMMC services, challenges in reporting of AEs in a large-scale VMMC programme are acknowledged. International and national standards of AE reporting in VMMC programmes are clear. As VMMC programmes transition to national ownership, challenges, strengths and learning from AE reporting systems are needed to support safety and quality of services.

National health information systems for achieving the Sustainable Development Goals.

OBJECTIVES: Achieving the Sustainable Development Goals will require data-driven public health action. There are limited publications on national health information systems that continuously generate health data. Given the need to develop these systems, we summarised their current status in low-income and middle-income countries. SETTING: The survey team jointly developed a questionnaire covering policy, planning, legislation and organisation of case reporting, patient monitoring and civil registration and vital statistics (CRVS) systems. From January until May 2017, we administered the questionnaire to key informants in 51 Centers for Disease Control country offices. Countries were aggregated for descriptive analyses in Microsoft Excel. RESULTS: Key informants in 15 countries responded to the questionnaire. Several key informants did not answer all questions, leading to different denominators across questions. The Ministry of Health coordinated case reporting, patient monitoring and CRVS systems in 93% (14/15), 93% (13/14) and 53% (8/15) of responding countries, respectively. Domestic financing supported case reporting, patient monitoring and CRVS systems in 86% (12/14), 75% (9/12) and 92% (11/12) of responding countries, respectively. The most common uses for system-generated data were to guide programme response in 100% (15/15) of countries for case reporting, to calculate service coverage in 92% (12/13) of countries for patient monitoring and to estimate the national burden of disease in 83% (10/12) of countries for CRVS. Systems with an electronic component were being used for case reporting, patient monitoring, birth registration and death registration in 87% (13/15), 92% (11/12), 77% (10/13) and 64% (7/11) of responding countries, respectively. CONCLUSIONS: Most responding countries have a solid foundation for policy, planning, legislation and organisation of health information systems. Further evaluation is needed to assess the quality of data generated from systems. Periodic evaluations may be useful in monitoring progress in strengthening and harmonising these systems over time.