Maputo

Women living with HIV (WLWH) are more likely to have persistent HPV infections and cervical cancer, especially in sub-Saharan Africa where healthcare resources are limited. Effective screening and treatment of pre-cancerous cervical changes are crucial to reduce cervical cancer burden in this population. This research compares two cervical treatments, thermal ablation (TA) and loop electrosurgical excision procedure (LEEP), to find the best method for treating cervical intraepithelial neoplasia grades 2 and 3 (CIN 2/3) and high-risk HPV infection in WLWH. The study evaluates TA, which uses heat to destroy abnormal cervical tissue, against LEEP, which removes cervical tissue through excision. Both treatments are applied to women diagnosed with precancerous cervical lesions. The study also assesses pain, side effects, and adverse events associated with each treatment. Researchers aim to identify factors that lead to treatment failure and develop a computer-based tool to predict which patients may not respond well to treatment. Participants attend screenings and receive one of the treatments. Follow-up occurs over 12 months to measure treatment success in curing CIN 2/3 and HPV infection. Researchers monitor safety, pain, and side effects throughout the study. The findings will help guide health policies to improve cervical cancer prevention and support patient adherence in areas with limited resources.

Researchers are evaluating doravirine combined with tenofovir and lamivudine as an alternative to dolutegravir combined with tenofovir and lamivudine or emtricitabine in adults living with HIV-1 who have never received treatment before. This Phase III, open-label, randomized, non-inferiority trial is conducted in multiple countries including Brazil, Cameroon, Côte d'Ivoire, France, Mozambique, and Thailand. The study aims to compare the effectiveness of these regimens by measuring the control of HIV viral load at 48 weeks. Participants will be randomly assigned to receive either doravirine plus tenofovir and lamivudine or dolutegravir plus tenofovir and lamivudine or emtricitabine, all given orally. The study will follow 610 participants for a total of 96 weeks after starting antiretroviral therapy. Primary evaluation focuses on the proportion of participants who achieve a viral load below 50 copies/mL at week 48. Secondary assessments will be performed at weeks 48 and 96. During the trial, participants will undergo regular monitoring including laboratory tests to measure viral load and kidney and liver function. The study will also assess safety and adherence to treatment. Participants must provide informed consent and will be closely followed throughout the study duration to ensure accurate outcome measurements and safety monitoring.

Termination of pregnancy was legalized in Mozambique in 2016 for any reason until 12 weeks, and up 16 weeks in cases of rape, and at any time for cases of fetal demise, severe fetal anomaly, or to protect a woman's physical or mental health. It is also legal up until 24 weeks in the case of a chronic infectious or degenerative disease. Termination of pregnancy can be accomplished either by induction of labor or by Dilation and Evacuation (D\&E). Typically, D\&E after 16 weeks is a two-day procedure. The first day is devoted to cervical preparation, where osmotic dilators are placed into the cervix and allowed to slowly soften and dilate the cervix. On the second day of the procedure the uterus is evacuated. Osmotic dilators are expensive and unavailable in most of Sub-Saharan Africa. An alternative strategy to cervical preparation has recently been developed by Dr. Yashica Robinson and has been described in a retrospective cohort study. This new technique involves using a Foley Catheter balloon (FB) inserted into the cervix to dilate the cervix over several hours with buccal misoprostol as an adjunct medication. After which, the procedure is completed using the dilation and evacuation procedure. However, Foley Balloon for cervical preparation before dilation and evacuation is still considered investigational. Both Foley Balloon and misoprostol are low cost and widely available in Africa and thus may be a safe and efficacious alternative to osmotic dilators. These two strategies of cervical preparation have never been directly compared in a prospective randomized clinical trial. This study aims to conduct a randomized controlled trial to evaluate the Foley Balloon for cervical preparation before D\&E. Specifically, our objective is to evaluate the Foley Balloon technique for cervical preparation before second trimester surgical abortion between 16 and 21 weeks estimated gestational age. The investigators propose to conduct a randomized controlled non-inferiority trial to compare procedure difficulty, complication rates, provider satisfaction, and patient satisfaction with a novel technique to prove that the Foley Balloon and misoprostol method is safe, effective, and acceptable to providers and patients.

Researchers are studying viral suppression in people living with HIV who have high viral loads despite being on dolutegravir (DTG)-based antiretroviral therapy (ART) for at least six months. The study aims to fill gaps in data about viral suppression rates without changing the ART regimen and to monitor the emergence of drug-resistant mutations linked to DTG and their effects on viral control. The research is conducted across multiple countries including Kenya, Mozambique, Tanzania, and Lesotho. Participants will continue their DTG-based ART throughout the study, which lasts up to 12 months. Those with viral loads of 200 copies/mL or higher will receive enhanced adherence counseling during scheduled visits every three months. The counseling includes at least three sessions focused on improving medication adherence and managing other causes of viral load increase. For participants who achieve viral suppression below 200 copies/mL during follow-up, an additional viral load test will be done after three months, with longer-term outcome data collected up to 24 months. Throughout the study, participants will have viral load testing at enrollment and every three months if suppression is not reached. Researchers will track viral suppression rates at 6 and 12 months and analyze factors linked to success, development of DTG resistance mutations, and opportunistic infections. The study also collects routine clinical data such as loss to follow-up and mortality. Participants may be evaluated for eligibility in a nested clinical trial focused on managing those who develop drug resistance during the cohort study.

Researchers are investigating the use of a rapid bedside test measuring the biomarker sTREM-1 to identify children admitted to hospitals in low and middle-income countries who are at higher risk of serious complications or death. The study is part of a larger project aiming to improve risk assessment and survival in children with fever syndromes. It focuses on children aged from 1 month to under 5 years who are admitted to hospital with fever or suspected severe illness and categorized as moderate to high risk by this biomarker test. The trial is a multi-country, randomized, double-blind, placebo-controlled study comparing the effects of oral L-citrulline supplementation versus placebo. Eligible children with moderate to high risk will receive either L-citrulline syrup or placebo twice daily for 28 days, with dosing adjusted by weight (200-300 mg/kg/day). The study is conducted in Mozambique and Ethiopia and aims to assess whether L-citrulline improves outcomes compared to placebo. Participants will be followed for six months with visits or phone contacts at days 3, 5, 7, 28, and month 6 after recruitment. Researchers will monitor adverse disease outcomes within 28 days, including death, neurological problems, kidney issues, need for organ support, shock, coma, severe respiratory distress, or hospital readmission. Safety and long-term health outcomes will also be assessed to evaluate the impact of the intervention.

BACKGROUND: The majority of people living with HIV (PLWH) on first-line antiretroviral therapy (ART) in low- and middle-income countries are on dolutegravir (DTG)-containing regimens. Different countries have adopted different approaches in the management of people on DTG-based first-line ART with repeat HIV viral load (VL) of \> 1,000 copies/mL after 3 months of enhanced adherence counselling. For example, Kenya recommends a drug resistance test (DRT) to guide on switch and the optimal second-line regimen; Mozambique and Tanzania recommend switch to 2 nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) without drug resistance testing; South Africa does not recommend switch from DTG or DRT for those who are on first-line DTG-containing regimens within the first 2 years of treatment, after which management is guided by possible DRT and expert opinion. The World Health Organization has recognised the role of drug resistance testing (DRT) in a treatment failure algorithm for people living with HIV receiving DTG-based treatment to minimise unnecessary switches from this regimen. The switch to PI has disadvantages including higher cost, higher pill burden, less convenient administration (often should be taken with food), more potential drug-drug interactions, poorer tolerability and more long-term toxicities. GOAL: To assess the efficacy and safety of remaining on DTG compared to switching to DRV/r among people failing DTG-based ART with at least one major DTG DRM. METHODS: This is a phase 3b, multi-country, open-label, two-arm, active-controlled randomized clinical trial (RCT) over 12 months describing the efficacy and safety of switching from DTG to DRV/r among PLWH age ≥ 3 years who are failing DTG-based ART with HIV-1 RNA ≥ 200 copies/mL and ≥ 1 major DTG-associated DRM (and most recent prior HIV-1 RNA ≥ 1,000 copies/mL after at least 6 months on DTG-based ART). The primary efficacy endpoint is the proportion of participants with HIV-1 RNA \< 200 copies/mL at month 6. The study will be conducted in 9 sites in Kenya, Mozambique, Tanzania and Lesotho targeting 392 participants including 30 children aged between 3 and 14 years old. The primary efficacy analysis will assess the difference in the proportion of participants with viral suppression at month 6 using the Cochran-Mantel-Haenszel method. This RCT is nested within an observational cohort study describing HIV-1 viral suppression of people with HIV-1 RNA value of ≥ 1,000 copies/mL after at least six months on DTG-based ART.

Researchers are evaluating the safety and effectiveness of new treatment combinations compared to the standard regimen for adults newly diagnosed with drug-sensitive pulmonary tuberculosis. This phase 2B/C open-label trial involves multiple stages and experimental treatment arms, including drugs like rifampicin, pyrazinamide, moxifloxacin, BTZ-043, alpibectir, ganfeborole, delpazolid, and others. The study aims to find optimized doses and new drug combinations that could improve treatment outcomes in this population. Participants will be randomly assigned to different treatment groups across three stages. Stage 1 compares the control regimen with two experimental rifampicin-containing regimens. Stage 2 adds a new experimental arm with BTZ-043, adjusting participant allocation ratios accordingly. Stage 3 begins after stages 1 and 2 complete recruitment and compares the control arm with two more experimental arms, including one containing alpibectir and ethionamide. Dosages and drug combinations vary by arm, with regimens administered mostly once daily by mouth. During the study, participants will be monitored up to 26 weeks to assess how quickly their tuberculosis cultures convert to negative and to measure changes in the amount of tuberculosis bacteria. Evaluations include clinical exams, chest X-rays, sputum tests, and safety monitoring. The total number of participants planned is up to 390 adults aged 18 to 65. The study includes thorough follow-up to understand treatment effects and safety in this group.

Researchers are studying the safety, tolerability, how the body processes the drug, and anti-mycobacterial effects of bedaquiline (TMC207) in children and adolescents from birth up to less than 18 years old who have confirmed or probable pulmonary multidrug resistant tuberculosis (MDR-TB). The study combines bedaquiline with a background regimen of MDR-TB medications following standard treatment guidelines. This is a Phase 2, open-label, multicenter, single-arm study. Participants receive bedaquiline in different dosages depending on their age group (four cohorts). For example, cohort 1 gets an adult tablet of 400 mg once daily for 2 weeks followed by 200 mg three times a week for 22 weeks. Younger cohorts receive age-appropriate doses, with administration schedules ensuring at least 48 hours between doses. The background MDR-TB medication regimen is given according to World Health Organization and local guidelines throughout the study. Participants are closely monitored through blood tests measuring drug levels at multiple times up to 120 weeks for some cohorts and up to 88 weeks for others. Researchers will also track adverse events and serious adverse events during the study. Other measures include maximum and minimum plasma concentration, time to peak concentration, drug clearance, and half-life. The total study duration varies by cohort, with ongoing safety and pharmacokinetic assessments to understand the drug's behavior and effects in children and adolescents with MDR-TB.

Infections are a leading cause of newborn deaths, with Group B Streptococcus (GBS) being the primary cause of sepsis and bacterial meningitis in infants during their first 90 days of life. Researchers are preparing for late-phase clinical trials of GBS vaccines designed for pregnant women to protect their unborn babies. The PROTECT project supports medical sites in Kenya, Malawi, Mozambique, and Uganda to establish uniform data collection and surveillance systems for GBS and other infections, aiming to improve vaccine trial readiness and vaccine safety monitoring in these regions. The study focuses on three main areas: establishing pregnancy exposure registries using electronic health records to track pregnancy and infant outcomes; developing sentinel site surveillance for laboratory-confirmed GBS infections in infants under 90 days old; and evaluating vaccine confidence among pregnant women and key community stakeholders. The project will develop tools and communication strategies to increase vaccine acceptance and participation in trials, strengthening healthcare systems for future vaccine delivery. Participants will include pregnant women, infants with confirmed GBS infections, and community stakeholders across the four countries. Researchers will collect and analyze health data, monitor infection rates, and assess attitudes toward vaccination. The study will track outcomes such as pregnancy and infant health, infection incidence, and vaccine confidence over multiple years, supporting ongoing safety monitoring and preparation for vaccine rollout through a coordinated network of maternal vaccine trial sites.

Researchers are evaluating faster, simpler, and less costly tests to diagnose tuberculosis (TB) in children under 15 years old. These studies, called Rapid Research in Diagnostics Development for TB Network (R2D2 Kids) and Assessing Diagnostics at Point-of-care for Tuberculosis in children (ADAPT for Kids), aim to reduce the global burden of childhood TB deaths by testing new point-of-care diagnostic tools. The challenge of collecting sputum from children and the low amount of bacteria present often delay diagnosis and treatment, making non-sputum based tests a high priority for development. The studies will assess several new TB diagnostic methods including oral swab molecular testing, which collects respiratory samples non-invasively; automated cough sound analysis using mobile devices and machine learning; automated lung sound analysis with a digital stethoscope and tablet; and chest X-ray computer aided detection using AI algorithms. These tests will be compared to standard definitions for childhood TB to evaluate their accuracy. Additionally, the usability and acceptability of the new tests will be studied through observations and surveys of the health workers who use them. Participants will be children under 15 years old who show symptoms or risk factors for TB, and health workers involved in routine TB testing. The studies will involve collecting test samples and evaluating the sensitivity and specificity of the new diagnostics over a 2-year period. Researchers will monitor how well the tests predict TB presence or absence and gather feedback on the practical use of the tests to better understand their potential impact for rapid TB diagnosis in children.