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.

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. 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. 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. 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. 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.

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. 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. 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. 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.

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.

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.

In Tanzania, loss to follow-up (LTFU) among adolescents and young adults living with HIV (AYLHIV) presents a significant challenge. A retrospective cohort study analysing data found that approximately 42% of adolescents on antiretroviral therapy (ART) were LTFU between 2014 to 2016. This study examined the predictors of LTFU among AYLHIV in Dar es Salaam during their first year of ART treatment. This retrospective cohort study utilized routine data collected in care and treatment centres among adolescents and young adults aged 10–24 years living with HIV in Dar es Salaam who were enrolled in HIV care from 2015–2019. The data were analysed using STATA 14. Descriptive statistics were summarized using frequencies and proportions. Kaplan–Meier method was used to determine failure probabilities within one year of ART initiation. The Fine and Gray test was conducted to report adjusted sub-hazard ratios (aSHRs) and cumulative incidence estimates for LTFU within one year of ART initiation, accounting for mortality as a competing risk. A total of 15,874 AYLHIVs enrolled in Care and Treatment Clinics between 2015 and 2019 were studied. The majority (10,913, 68.7%) were young adults, and 13,160 (84.4%) were female. The percentage of LTFUs within one year of ART initiation was 15%. The significant predictors of LTFU were age 20–24 years, having a CD4 cell count between 350 and 499, receiving care in healthcare facilities located in the Ubungo district and being enrolled in care between 2018 and 2019. Receiving care at private healthcare facilities, having a tuberculosis co-infection, and being classified as WHO Stage III were all associated with a reduced risk of LTFU in ART care. This study found that adolescents and young people in Tanzania experience 15% rates of LTFU in ART care, within one year of ART initiation. Therefore, HIV service providers need to pay particular attention to the AYLHIV and factors that influence LTFU in ART care. The increasing incidence of LTFU necessitates the implementation of effective and friendly tracing interventions to identify AYLHIV patients who have become LTFU to re-engage them in care.