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

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

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.

Why did I stop? And why did I restart? Perspectives of women lost to follow-up in option B+ HIV care in Dar es Salaam, Tanzania.

BACKGROUND: Despite an increased uptake of option B+ treatment among HIV- positive pregnant and breastfeeding women, retaining these women in care is still a major challenge. Previous studies have identified factors associated with loss to follow-up (LTFU) in HIV care, however, the perspectives from HIV-positive pregnant and breastfeeding women regarding their LTFU in option B+ needs further exploration. We explored reasons for LTFU and motivation to resume treatment among HIV-positive women initiated in option B+ in an Urban setting. METHODS: A descriptive qualitative study was conducted at three public care and treatment clinics (CTC) (Buguruni health center, Sinza hospital, and Mbagala Rangitatu health center) in Dar es Salaam, Tanzania between February and May 2017. In-depth interviews were conducted with 30 HIV-positive pregnant and breastfeeding women who were lost to follow up in the option B+ regimen. Analysis of data followed content analysis that was performed using NVivo 10 computer-assisted qualitative data analysis software. RESULTS: Eleven women were lost to follow-up and did not resume Option B+, while 19 had resumed treatment. The study indicated a struggle with long term disease amongst HIV-positive pregnant and breastfeeding women initiated in option B+ treatment. The reported reasons contributing to LTFU among these women appeared in three categories. The contribution of LTFU in the first category namely health-related factors included medication side effects and lack of disease symptoms. The second category highlighted the contribution of psychological factors such as loss of hope, fear of medication side effects and HIV-related stigma. The third category underscored the influence of socio-economic statuses such as financial constraints, lack of partner support, family conflicts, non-disclosure of HIV-positive status, and religious beliefs. Motivators to resume treatment after LTFU included support from health care providers and family members, a desire to protect the unborn child from HIV-infection and a need to maintain a healthy status. CONCLUSION: The study has highlighted the reasons for LTFU and motivation to resume treatment among women initiated in Option B+. Our results provide further evidence on the need for future interventions to focus on these factors in order to improve retention in life-long treatment.

"Experiences with disclosure of HIV-positive status to the infected child": Perspectives of healthcare providers in Dar es Salaam, Tanzania.

BACKGROUND: The specific age to which an HIV infected child can be disclosed to is stipulated to begin between ages 4 and 6 years. It has also been documented that before disclosure of HIV positive status to the infected child. Health care providers should consider children's cognitive-developmental ability. However, observation and situation analysis show that, health care providers still feel uncomfortable disclosing the HIV positive status to the infected child. The aim of the study was to explore healthcare providers' experiences in disclosure of HIV-positive status to the infected child. METHODS: A qualitative study involving 20 health care providers who attend HIV-positive children was conducted in September, 2014 in Dar es Salaam, Tanzania. Participants were selected from ten HIV care and treatment clinics (CTC) by purposive sampling. An interview guide, translated into participants' national language (Kiswahili) was used during in-depth interviews. Sampling followed the principle of data saturation. The interviews focused on perspectives of health-care providers regarding their experience with paediatric HIV disclosure. Data from in-depth interviews were transcribed into text; data analysis followed qualitative content analysis. RESULTS: The results show how complex the process of disclosure to children living with HIV can be to healthcare providers. Confusion was noted among healthcare providers about their role and responsibility in the process of disclosing to the HIV infected child. This was reported to be largely due to unclear guidelines and lack of standardized training in paediatric HIV disclosure. Furthermore, healthcare providers were concerned about parental hesitancy to disclose early to the child due to lack of disclosure skills and fear of stigma. In order to improve the disclosure process in HIV infected children, healthcare providers recommended further standardized training on paediatric HIV disclosure with more emphasis on practical skills and inclusion of disclosure content that is age appropriate for children with HIV. DISCUSSION: The disclosure process was found to be a complex process. Perspectives regarding disclosure in children infected with HIV varied among healthcare providers in terms of their role in the process, clear national guidelines and appropriate standardized training for paediatric disclosure. Consistent with other studies, healthcare providers reported difficulties during disclosure because parents /guardians largely fear blame, social stigma, child's negative emotional reaction when disclosed to and have concerns about the child being too young and immature to understand the HIV condition. CONCLUSIONS: In order to prevent inconsistencies during the disclosure process, it is important to have in place clear guidelines and standardized paediatric HIV disclosure training for healthcare providers. This would help improve their skills in paediatric disclosure, leading to positive health outcomes for children infected with HIV.

HIV viral suppression in the era of dolutegravir use: Findings from a national survey in Tanzania.

BACKGROUND: Tanzania has made significant progress in improving access to HIV care and treatment. However, virologic suppression among people living with HIV (PLHIV) has not been fully realized. In March 2019, Tanzania introduced a World Health Organization (WHO)-recommended dolutegravir-based regimen as the default first-line regimen. Eighteen months later we investigated the HIV viral suppression rates and the factors associated with lack of viral suppression among PLHIV (children and adults) in Tanzania. METHODOLOGY: A cross-sectional survey was conducted from September to December 2020 among PLHIV on antiretroviral therapy (ART) in Tanzania. Whole blood samples, demographic data and clinical information were obtained from eligible adults (≥15 years) and children (< 15 years) attending thirty-six HIV care and treatment centres located in 22 regions of Tanzania mainland. A whole blood sample from each participant was processed into plasma and HIV viral load was estimated using real-time PCR. HIV viral suppression was defined at a cut-off of < 50 copies/mL as recommended by WHO. Analyses were conducted using descriptive statistics to establish the national representative prevalence of viral suppression, and logistic regression analyses to determine independent factors associated with non-suppression. RESULTS: A total of 2,039 PLHIV on ART were recruited; of these, adults and children were 57.5% (n = 1173) and 42.5% (n = 866), respectively. Among the adult population, the mean age and standard deviation (SD) was 42.1 ± 12.4 years, with 64.7% being female. Among children, the mean age and SD were 9.6 ± 3 years, and 53.2% were female. Overall viral suppression at < 50 copies/mL (undetectable) was achieved in 87.8% of adults and 74.4% of children. Adults and children on dolutegravir-based regimen recorded viral suppression rates of 89.7% and 85.1% respectively. Factors independently associated with lack of viral suppression status in the adult population were age and ART adherence while in the children population, the factors were sex, ART adherence, and current ART regimen (p<0.05). CONCLUSION: Dolutegravir-based regimens are promising to help attain epidemic control in Tanzania. More efforts especially on ART adherence are needed to attain optimal treatment outcomes for children and adults PLHIV in Tanzania.

Diagnostic delay in ankle and foot tuberculosis resulting in tuberculoma and tuberculous meningitis in a middle-aged female: A case report.

A middle-aged woman presents with chronic foot arthritis which progressed to a non-healing ulcer, which was unresponsive to conventional antibiotics and debridement. She then developed cerebral manifestations and was empirically treated with antitubercular medications which led to healing of the ulcer. Unfortunately, delays in initiating treatment resulted in development of other extrapulmonary tuberculosis complications such as cerebral tuberculoma with tuberculous meningitis. She was subsequently diagnosed with neurocysticercosis which continued to worsen during her hospital stay. She eventually succumbed to her illness due to the complications and a possible nosocomial infection. This case highlights the challenges with diagnosis of uncommon presentations of common diseases in an endemic area, leading to diagnostic delays and development of serious complications.

Cryptococcal antigen prevalence in HIV-infected Tanzanians: a cross-sectional study and evaluation of a point-of-care lateral flow assay.

OBJECTIVES: Cryptococcal antigen (CRAG) screening at antiretroviral therapy (ART) initiation and pre-emptive antifungal treatment for those testing positive could prevent many cases of cryptococcal meningitis (CM). To investigate whether CRAG screening would be feasible in Tanzania, we conducted a cross-sectional study measuring CRAG prevalence in ART clinic patients and comparing the novel lateral flow assay (LFA) with the cryptococcal latex agglutination (LA) test. METHODS: Consecutive HIV-infected outpatients with CD4 counts <200 cells/µL, who were ART naive or had been on ART for <6 months, were screened for CRAG using the LA and LFA kits. For further assay validation, HIV-infected inpatients with suspected cryptococcal disease were also tested using the LA and LFA kits. RESULTS: Cryptococcal antigen was detected in seven of 218 ART clinic attendees (3%). Six patients (5%) with CD4 cell counts ≤100 cells/µL (n = 124) were CRAG-positive. Agreement between the LA and LFA test in the 218 outpatients was 100%. Another 101 inpatients were tested for CRAG, of whom 56 (55%) were CRAG-positive on both the LA and LFA tests. One patient was positive using the LFA test but negative on the LA test. The overall agreement between the two assays was 99.7%, kappa coefficient 0.99 (standard error 0.06, P < 0.001). CONCLUSIONS: Five percentage of ART clinic patients with CD4 cell counts ≤100 cells/µL in northern Tanzania had asymptomatic cryptococcal antigenaemia, suggesting that CRAG screening would be worthwhile in the Tanzanian ART programme. The LFA is a reliable, cheap and practical alternative to LA for detection of CRAG.

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.

Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM) causes an estimated 180,000 deaths annually, predominantly in sub-Saharan Africa, where most patients receive fluconazole (FLC) monotherapy. While relapse after FLC monotherapy with resistant strains is frequently observed, the mechanisms and impact of emergence of FLC resistance in human CM are poorly understood. Heteroresistance (HetR) - a resistant subpopulation within a susceptible strain - is a recently described phenomenon in Cryptococcus neoformans (Cn) and Cryptococcus gattii (Cg), the significance of which has not previously been studied in humans. METHODS: A cohort of 20 patients with HIV-associated CM in Tanzania was prospectively observed during therapy with either FLC monotherapy or in combination with flucytosine (5FC). Total and resistant subpopulations of Cryptococcus spp. were quantified directly from patient cerebrospinal fluid (CSF). Stored isolates underwent whole genome sequencing and phenotypic characterization. RESULTS: Heteroresistance was detectable in Cryptococcus spp. in the CSF of all patients at baseline (i.e., prior to initiation of therapy). During FLC monotherapy, the proportion of resistant colonies in the CSF increased during the first 2 weeks of treatment. In contrast, no resistant subpopulation was detectable in CSF by day 14 in those receiving a combination of FLC and 5FC. Genomic analysis revealed high rates of aneuploidy in heteroresistant colonies as well as in relapse isolates, with chromosome 1 (Chr1) disomy predominating. This is apparently due to the presence on Chr1 of ERG11, which is the FLC drug target, and AFR1, which encodes a drug efflux pump. In vitro efflux levels positively correlated with the level of heteroresistance. CONCLUSION: Our findings demonstrate for what we believe is the first time the presence and emergence of aneuploidy-driven FLC heteroresistance in human CM, association of efflux levels with heteroresistance, and the successful suppression of heteroresistance with 5FC/FLC combination therapy. FUNDING: This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z and the Daniel Turnberg Travel Fellowship.

Reversible Deafness and Blindness in a Patient with Cryptococcal Meningitis in Tanzania.

Cryptococcal meningitis is a common and devastating complication of advanced HIV, and is most prevalent in low resource settings in sub Saharan Africa. Raised intracranial pressure is one of the hallmarks of the disease, which can lead to visual and hearing loss and ultimately death. We present the case of a patient with visual and hearing impairment secondary to Cryptococcal meningitis successfully managed by serial cerebrospinal fluid drainage. This case highlights some of the challenges of managing this severe opportunistic infection in a low resource setting.