Upscaling cervical cancer screening and treatment for women living with HIV at a rural referral hospital in Tanzania: protocol of a before-and-after study exploring HPV testing and novel diagnostics.

BACKGROUND: Cervical cancer (CC) is nearly always caused by persistent human papillomavirus (HPV) infection. It is the most common cancer among women living with HIV (WLWH) and is the leading cause of cancer-related death in women in East Africa, with 10,241 new cases reported in Tanzania in 2020. In 2019, the World Health Organization (WHO) presented a global strategy for the elimination of CC as a public health problem, proposing targets to meet by 2030 for HPV vaccine coverage (90% of all 15-year-old girls), CC screening (70% of all women once at 35 and again at 45 years of age) and treatment delivery, to be scaled at national and subnational levels with a context-sensitive approach. This study aims to evaluate the upscaling of screening and treatment services at a rural referral hospital in Tanzania in order to address the second and third WHO targets. METHODS: This is an implementation study with a before-and-after design performed at St. Francis Referral Hospital (SFRH) in Ifakara (south-central Tanzania). CC screening and treatment services are integrated within the local HIV Care and Treatment Center (CTC). The standard of care, consisting of visualization of the cervix with acetic acid (VIA) and cryotherapy has been up-scaled with self-sampled HPV testing and also involved the introduction of mobile colposcopy, thermal ablation and loop electrosurgical excision procedure (LEEP). Participants are WLWH aged 18 to 65 years. Outcome measures included the percentage of women screened, HPV prevalence and genotype, and adherence to screening, treatment and follow-up plan. Additionally, we will explore the performance of novel diagnostic tests (QG-MPH®, Prevo-Check® and PT Monitor®), which share the features of being manageable and inexpensive, and thus a potential tool for effective triage in HPV high-prevalence cohorts. DISCUSSION: The study will provide relevant information about HPV prevalence and persistence, as well as reproductive and lifestyle indicators in a CC high-risk cohort of WLWH and about upscaling screening and treatment services at the level of a rural referral hospital in Tanzania. Furthermore, it will provide exploratory data on novel assays. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05256862, date of registration 25/02/2022. Retrospectively registered.

Failure to return pillbox is a predictor of being lost to follow-up among people living with HIV on antiretroviral therapy in rural Tanzania.

OBJECTIVES: Pill count is used to assess drug adherence in people living with HIV (PLHIV). Carrying a pillbox is associated with fear of concealment and stigma and might indicate poor adherence and predict someone who will be lost to follow-up (LTFU). We therefore assessed the association between pillbox return and being LTFU in rural Tanzania. METHODS: This is a nested study of the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). We included PLHIV aged ≥ 18 years enrolled in KIULARCO between January 2013 and March 2019 with follow-up through January 2020, who were on antiretroviral treatment (ART) for ≥ 6 months. Baseline was defined as the latest ART initiation or KIULARCO enrolment. We determined the association between time-dependent failed pillbox return updated at every visit and LTFU using Kaplan-Meier estimation and Cox models. RESULTS: Among 2552 PLHIV included in the study, 1735 (68.0%) were female, 959 (40.3%) had a WHO stage III/IV and 1487 (66.4%) had a CD4 cell count < 350 cells/µL. The median age was 38.4 years [interquartile range (IQR): 31.7-46.2]. During a median follow-up of 33.1 months (IQR: 17.5-52.4), 909 (35.6%) participants were LTFU, 43 (1.7%) died and 194 (7.6%) had transferred to another clinic. The probability of being LTFU was higher among PLHIV with failed pillbox return than among those who returned their pillbox [30.0%, 95% confidence interval (CI): 26.8-33.2% vs. 19.4%, 95% CI: 17.4-21.6%, respectively, at 24 months (hazard ratio = 1.67, 95% CI: 1.46-1.90; p < 0.001)]. CONCLUSIONS: Failed pillbox return was associated with a higher risk of being LTFU and could be used as a simple tool to identify PLHIV for appropriate interventions to reduce their chance of being LTFU.

Recognition and management of clinically significant drug-drug interactions between antiretrovirals and co-medications in a cohort of people living with HIV in rural Tanzania: a prospective questionnaire-based study.

BACKGROUND: The extent to which drug-drug interactions (DDIs) between antiretrovirals (ARVs) and co-medications are recognized and managed has not been thoroughly evaluated in limited-resource settings. OBJECTIVES: This prospective questionnaire-based study aimed to determine the prevalence and risk factors for unrecognized/incorrectly managed DDIs in people living with HIV followed-up at the Chronic Diseases Clinic of Ifakara (CDCI) and enrolled in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). METHODS: We prospectively included ARV-treated adults receiving ≥1 co-medication coming for a follow-up visit at the CDCI between March and July 2017. Using a structured questionnaire, physicians were requested to identify potentially clinically significant DDIs in the prescribed treatment, to provide recommendations for their management and to indicate any hurdles to implement the recommendations. Prescriptions were subsequently screened for DDIs using the Liverpool DDIs database. Identified clinically significant DDIs and their recommended management according to the DDIs database were compared with the information provided in the questionnaires. RESULTS: Among 334 participants, the median age was 47 years (IQR = 40-56 years), 69% were female and 82% had ≥1 non-communicable disease (NCD). Overall, 129 participants had ≥1 clinically relevant DDI, which was not recognized and/or incorrectly managed in 56 participants (43%). Of those, 6 (11%) were due to limited monitoring options or medication affordability issues. In the multivariable logistic regression, the presence of ≥1 NCD was associated with an increased risk for unrecognized/incorrect DDI management (OR = 15.8; 95% CI = 1.8-139.6). CONCLUSIONS: Recognition/appropriate management of DDIs is suboptimal, highlighting the need for educational programmes, pharmacovigilance activities and increased access to medications and monitoring options. This should become a focus of HIV programmes given the increasing burden of NCDs in sub-Saharan Africa.