Maputo

Women living with HIV WLWH are more likely to develop persistent HPV infection and cervical cancer CC. Effective screening and treatment of pre-cancerous cervical abnormalities are critical to reduce the burden of cervical cancer, especially in sub-Saharan Africa where most WLWH live and resources are limited. This research aims to compare two treatment methods, thermal ablation TA and loop electrosurgical excision procedure LEEP, to determine which is more effective in treating cervical pre-cancerous lesions CIN 23 and HPV infection, and to identify factors linked to treatment failure. The study randomly assigns WLWH who test positive on cervical screening to receive either TA or LEEP. TA uses heat to destroy abnormal cervical tissue and is performed immediately after taking biopsies and curettage if needed. LEEP involves removing cervical tissue and is done following standard procedures, usually without prior biopsies. The study also evaluates pain and side effects related to each treatment and aims to develop an automated tool to predict treatment failure. Participants will undergo assessments including biopsies, colposcopy, and endocervical curettage as needed. Researchers will monitor treatment success at 12 months by comparing cure rates of CIN 23 lesions between the two methods. Safety, side effects, and pain are also tracked. The trial runs until December 2027 and is conducted by Instituto Nacional de Sade, Mozambique, focusing on women aged 25 to 49 living with HIV.

Researchers are evaluating doravirine as an alternative to dolutegravir in people newly diagnosed with HIV-1 infection who have not yet received treatment. This Phase III, open-label, randomized clinical trial aims to determine if doravirine combined with tenofovir and lamivudine is not less effective than dolutegravir combined with tenofovir and lamivudine or emtricitabine. The study will be conducted across multiple countries including Brazil, Cameroon, Cte dIvoire, France, Mozambique, and Thailand, enrolling 610 participants. Participants will be randomly assigned to one of two groups one receiving doravirine 100 mg plus tenofovir DF 300 mg and lamivudine 300 mg daily, and the other receiving dolutegravir 50 mg plus tenofovir DF 300 mg and either lamivudine or emtricitabine daily. The treatment period will last for 96 weeks after starting antiretroviral therapy ART, with primary assessment at week 48 to measure viral suppression. During the study, participants will undergo evaluations to monitor viral load, drug resistance, metabolic health, body weight changes, liver and kidney function, cardiovascular status, and mental health. Adherence to ART will be tracked, and blood samples will be taken to measure drug levels and immune cell counts. The research team will review virological efficacy and safety outcomes at weeks 48 and 96, supporting a comprehensive understanding of the treatments effects over nearly two years of participation.

This research aims to evaluate the Foley Balloon technique combined with misoprostol for preparing the cervix before second trimester surgical abortion between 16 and 21 weeks gestational age. The study compares this method to the standard use of osmotic dilators Laminaria to assess if the Foley Balloon and misoprostol approach is not worse than the usual method. Additionally, the study will explore patient and provider satisfaction with both cervical preparation methods. Participants are randomly assigned to one of two groups. One group will receive a Foley Balloon catheter placed trans-cervically, inflated with saline, along with buccal misoprostol. The other group will have Laminaria devices placed in the cervix according to gestational age. Cervical preparation typically occurs on the first day, followed by dilation and evacuation D&E on the second day to complete the abortion procedure. Participants will undergo the cervical preparation procedure followed by D&E, with assessments including total procedure time, operative time, cervical dilation, complication rates, and pain levels. Satisfaction questionnaires will be completed by both patients and providers. The study spans the preparation and procedure days, with monitoring for safety and effectiveness outcomes. The total procedure time will be about 15-20 minutes during D&E completion, while complications and satisfaction are evaluated over 1-2 days.

Researchers are studying people living with HIV-1 infection who are on dolutegravir DTG-based antiretroviral therapy ART but have a viral load above 1,000 copiesmL after at least six months of treatment. The goal is to understand viral suppression rates and the emergence of DTG-associated drug-resistant mutations in these individuals. This multi-country prospective observational study takes place in Kenya, Mozambique, Tanzania, and Lesotho, addressing gaps in data about managing virologic failure without changing the ART regimen. Participants will continue their DTG-based ART for up to 12 months while receiving enhanced adherence counseling if their viral load remains above 200 copiesmL. Study visits and viral load testing happen at enrollment and every three months during the active follow-up period. Enhanced adherence counseling includes at least three sessions per visit to support medication adherence and address other causes of viral increase. The study also collects routine program data for up to 24 months to assess how well viral suppression lasts over time. During the study, participants undergo viral load testing, counseling, and assessments at regular intervals. Researchers will analyze viral suppression rates at 6 and 12 months and evaluate factors that predict suppression or the development of drug resistance. They will also monitor the patterns and timing of drug-resistant mutations and opportunistic infections. The study plans to enroll 6,600 participants and may invite eligible individuals to join a nested randomized clinical trial focusing on managing drug resistance.

Researchers are investigating how a rapid bedside test measuring the biomarker sTREM-1 can identify hospitalized children at higher risk of serious health problems or death in low and middle-income countries. This study aims to see if this test can help guide treatment and improve survival and health after discharge. The trial is part of a larger project focused on improving outcomes for children with fever syndromes. The study involves children aged 1 month to under 5 years who are admitted to hospital and identified as moderate to high risk by the biomarker test. Participants are randomly assigned to receive either L-citrulline syrup, a supplement involved in nitric oxide production, or a placebo. The treatment is given twice daily by weight for 28 days. The trial is conducted in multiple sites in Mozambique and Ethiopia and uses a double-blind, placebo-controlled design. Participants will be followed for six months with visits at the hospital, home, or by phone on days 3, 5, 7, 28, and at 6 months. Researchers will monitor adverse outcomes including death, neurological problems, kidney events, organ support needs, shock, coma, respiratory distress, or hospital readmission within 28 days. Safety events and longer-term health after discharge will also be assessed to understand the treatments impact and overall child survival.

Researchers are studying the management of drug resistance in people living with HIV who are on dolutegravir DTG-based antiretroviral therapy but experience treatment failure due to drug-resistant mutations. This phase 3b randomized clinical trial aims to compare the effectiveness and safety of continuing DTG versus switching to ritonavir-boosted darunavir DRVr in patients with HIV-1 RNA levels above 200 copiesmL and at least one major DTG-associated drug resistance mutation. The study addresses gaps in current treatment strategies across several countries. Participants will be randomly assigned to one of two groups one will continue their existing DTG-based ART regimen, and the other will switch to a DRVr-based ART regimen. The dosing will be based on weight, and the study will take place over 12 months at multiple sites in Kenya, Mozambique, Tanzania, and Lesotho. The primary measure is the proportion of participants achieving viral suppression with HIV-1 RNA below 200 copiesmL at 6 months. During the trial, participants will have regular monitoring of their viral load and drug resistance mutations, along with assessments of treatment adherence, safety, and patient satisfaction. Additional outcomes include viral suppression rates at 12 months, incidence of adverse events, and changes in CD4 counts. The study includes children aged 3 years and older and plans to enroll 392 participants. Follow-up and data collection will support understanding optimal treatment management for this population.

Researchers are investigating new treatment options for adults with newly diagnosed, drug-sensitive pulmonary tuberculosis through a phase 2BC open-label platform study. The trial compares several experimental drug regimens with a standard control treatment to assess efficacy and safety. Participants include adults aged 18 to 65 years with confirmed pulmonary tuberculosis sensitive to rifampicin and isoniazid. The study aims to optimize doses of existing drugs and introduce new medications to improve treatment outcomes. The study is divided into three stages. In stage 1, participants are randomly assigned to the control or one of two experimental arms containing high-dose rifampicin and other drugs for 12 to 17 weeks. Stage 2 adds an experimental arm including the drug BTZ-043, with participants allocated across four arms in varying ratios. Stage 3 begins after stages 1 and 2 complete enrollment, comparing the control arm with two new experimental arms involving novel drug combinations. Treatments are given once daily, with dosages adjusted by arm and weight. Participants will undergo sputum testing, chest X-rays, and molecular tests to confirm tuberculosis and drug sensitivity before enrollment. During the study, researchers will monitor participants through regular clinical assessments, laboratory tests, and electrocardiograms to track treatment response and safety. The main outcomes measured include time to stable culture conversion and changes in mycobacterial load. Safety is evaluated by recording adverse events and laboratory abnormalities over the treatment period, with follow-up continuing up to 12 months after randomization.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and anti-mycobacterial activity of bedaquiline TMC207 combined with a standard background regimen of medications in children and adolescents aged from birth up to less than 18 years who have confirmed or probable pulmonary multidrug resistant tuberculosis MDR-TB. This phase 2 study aims to better understand how the drug works in this population and assess its effects alongside other MDR-TB treatments. Participants are grouped into four age-based cohorts, each receiving a dose of bedaquiline adjusted for their age and weight. Cohorts 1 and 2 include older children and adolescents who start with daily dosing for two weeks followed by three times weekly dosing for 22 weeks. Younger children in Cohorts 3 and 4 receive weight-based doses with similar schedules. All participants take bedaquiline along with a background regimen of MDR-TB medications according to WHO and national guidelines. During the study, participants undergo regular monitoring of drug levels in their blood at various weeks up to 120 weeks for older cohorts and 88 weeks for the youngest cohort. Researchers also track adverse events, treatment outcomes, and time to culture conversion from clinical samples. The study involves long-term follow-up to evaluate safety, drug behavior, and treatment success over time.

Group B Streptococcus GBS is a leading cause of sepsis and bacterial meningitis in newborns during the first 90 days of life, contributing significantly to newborn deaths. Researchers are preparing for maternal GBS vaccine trials in Africa to improve infection prevention through better data collection, surveillance, and vaccine confidence. The PROTECT project supports sites in Kenya, Malawi, Mozambique, and Uganda to establish uniform pregnancy and infant health data, monitor GBS incidence, and understand factors affecting vaccine acceptance. The study consists of three main parts creating pregnancy exposure registries using electronic health records to track pregnancy and infant outcomes conducting a prospective observational GBS surveillance study among infants under 90 days with confirmed GBS infection at sentinel sites and assessing vaccine confidence through surveys and interviews with pregnant women, healthcare workers, and community leaders. These activities aim to strengthen healthcare systems for future vaccine trials and rollout. Participants include pregnant women and their infants up to hospital discharge for the registry infants under 90 days with confirmed GBS infection for surveillance and pregnant women, healthcare workers, and community stakeholders for vaccine confidence research. The study involves collecting and analyzing medical records, microbiological data, and survey responses over periods ranging from 12 months to two years. Researchers will monitor pregnancy and infant outcomes, GBS infection rates, and vaccine knowledge to prepare for vaccine safety monitoring and effective vaccine implementation.

Researchers are evaluating new, faster, simpler, and less expensive diagnostic tests for 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 TB in Children ADAPT for Kids, aim to reduce childhood deaths caused by TB by addressing challenges in current diagnosis methods, especially the difficulty of obtaining sputum samples from children. The studies will assess how well these novel tests detect TB compared to established definitions and will also evaluate how easy and acceptable the tests are for health workers to use. The studies involve evaluating several novel TB diagnostic tests including oral swab molecular testing, automated cough sound analysis using mobile devices, automated lung sound analysis with digital stethoscopes, and chest X-ray computer-aided detection using artificial intelligence. These tests are non-invasive and designed for point-of-care use. The evaluation will be conducted among children suspected of having TB, enrolling about 250 participants per year at three different sites. Additionally, about 30 health workers will participate to assess the usability of these new tests. New tests will be evaluated as they become ready for field testing. Participants will be monitored to determine the proportion of positive and negative results from the new tests among children with and without TB over two years. The study includes collecting respiratory samples using swabs, recording cough and lung sounds, and performing chest X-rays analyzed by AI. Health workers experiences with the tests will be gathered through observations and surveys. The total participation time varies with follow-up visits planned to assess diagnostic accuracy and usability. Safety and consent procedures are in place to protect participants, and the studies continue until September 2026.