Phase I/II Multi-center, Open-Label Pharmacokinetic, Safety, Tolerability and Antiviral Activity of Dolutegravir, a Novel Integrase Inhibitor, in Combination Regimens in HIV-1 Infected Infants, Children and Adolescents.

Duration:
13 years

Objectives:
– To select a dolutegravir dose for chronic dosing; to determine the safety and tolerability of the dose,
– To evaluate the steady-state pharmacokinetics of dolutegravir in combination with other antiretrovirals
– To determine the dose of dolutegravir that achieves the targeted C24h and AUC0-24 PK parameters in the population.

Principal Investigator:
Dr. Maxensia Owor

Very Early Intensive Treatment of HIV-Infected Infants to Achieve HIV Remission: A Phase I/II Proof of Concept Study.

Duration:
5 years

Study Population:High-Risk,
– Cohort 1: Infants aged ≤ 48 hours of birth born to women with HIV infection who did not receive any antiretrovirals (ARVs) during pregnancy and ART-Started,
– Cohort 2: Infants ≤ 10 days of age with documented in utero HIV infection who initiated antiretroviral therapy (ART) outside of the study within 48 hours of birth
– Mothers of infants in both cohorts

Objectives:
Primary Objective:
To assess HIV remission (remission is defined as having no confirmed plasma HIV RNA  LOD for 48 weeks following ART cessation) among HIV-infected neonates who initiate ART within 48 hours of birth.

Secondary Objectives:
– To assess the safety of very early ART in neonates.
– To assess the PK of NVP in neonates and young infants in order to determine the NVP dose needed to maintain NVP concentrations between 3,000 and 10,000 ng/mL required for HIV treatment.
– To describe LPV exposures when dosed with NVP in neonates and young infants.
– To assess the relationship between time to reach confirmed plasma HIV RNA < LOD and achievement of the virologic and immunologic criteria for ART cessation among infants who have no evidence of viral rebound.
– To assess the extent of HIV persistence in infants who achieve HIV remission.
– To evaluate immune activation and host and viral determinants, including maternal factors and HIV-specific immune responses, associated with HIV remission.

Pharmacokinetic Properties of Antiretroviral Drugs during Pregnancy.

Pharmacokinetics, Feasibility, Acceptability, and Safety of Oral Pre-Exposure Prophylaxis for Primary HIV Prevention during Pregnancy and Postpartum in Adolescents and Young Women and their Infants.

Phase III Study of the Virologic Efficacy and Safety of Dolutegravir-Containing versus Efavirenz-Containing Antiretroviral Therapy Regimens in HIV-1-Infected Pregnant Women and their Infants.

Study Population:
Pregnant women (aged ≥18 years) with confirmed HIV-1 infection and at 14-28 weeks’ gestation

Duration:
48 months

Objective:
To compare the virologic efficacy and safety of three antiretroviral (ARV) regimens, dolutegravir plus emtricitabine/tenofovir alafenamide, dolutegravir plus emtricitabine/tenofovir disoproxil fumarate, and efavirenz/emtricitabine/tenofovir disoproxil fumarate in pregnant women living with HIV-1 and to compare the safety of these regimens for their infants.

Principal Investigator:
Dr. Deo Wabwire

Study Coordinator:
Dr. Joel Maena

Phase I/II Study of the Safety, Acceptability, Tolerability, and Pharmacokinetics of Oral and Long-Acting Injectable Cabotegravir and Long-Acting Injectable Rilpivirine in Virologically Suppressed HIV-Infected Children and Adolescents.

Principal Investigator:
Dr. Maxensia Owor:

MTN-001 was a Phase II trial that looked at how tenofovir is absorbed in the body as either an oral tablet or a vaginal gel, as well as women’s preferences for and ability to adhere to the daily regimens of each approach.

VOICE was a Phase 2B, multi-site, five-arm, randomized, controlled trial. A total of 5029 women were randomized to five study arms in a 1:1:1: 1:1 ratio. Secondary objectives focused on adherence/behavioral factors, HIV-1 drug resistance (among those who become HIV-infected during the study), pharmacokinetic parameters, and the potential for delayed seroconversion during an off-product period scheduled at the end of study participation.

The BMD Substudy was an observational substudy of VOICE designed to assess the impact of oral TDF and oral FTC/TDF on bone mineral density.

VOICE D (MTN-003D) was a behavioral sub-study of VOICE that aimed to understand women’s actual and reported use of study products and sexual behavior during their participation in VOICE.

MTN-015 was a multi-site, prospective, observational cohort study of women following HIV-1 seroconversion in microbicide trials of ARV-based microbicides or oral pre-exposure prophylaxis (PrEP).

MTN-016 or EMBRACE (Evaluation of Maternal and Baby Outcome Registry After Chemoprophylactic Exposure) was an observational study and data registry designed to understand the effects, if any, the use of ARV-based HIV prevention products may have on pregnancy and infant outcomes.

MTN-020, or ASPIRE (A Study to Prevent Infection with a Ring for Extended Use), was a Phase III study to determine whether a vaginal ring containing the ARV drug dapivirine is a safe and effective method for protecting against the sexual transmission of HIV when used by women for a month at a time.

MTN-025, the HIV Open-label Prevention Extension (HOPE) trial, was a multi-site, open-label, Phase 3B trial. Eligible HIV-uninfected former ASPIRE participants were offered a silicone elastomer VR containing 25 mg of dapivirine.

MTN-032 was an exploratory study primarily designed to identify factors that may have affected participant adherence to study product in MTN-020 (ASPIRE) and MTN-025 (HOPE).

Safety and Adherence to a Vaginal Dapivirine ring vs Oral TDF/FTC in female Adolescent

MTN-041 was a multi-site qualitative acceptability study that utilized focus group discussions and in-depth interviews to explore the attitudes of community members and key informants from the community about the use of a Dapivirine Vaginal Ring or oral PrEP (FTC/TDF) during pregnancy and breastfeeding.

MTN-042 is a Phase 3b, open-label, multi-site, randomized trial designed to assess the safety, adherence, and acceptability profiles of the dapivirine Varginal Ring and Truvada (FTC/TDF) oral tablet when used during pregnancy

MTN-043 was a Phase 3B, open-label, randomized, multi-site, mother-infant pair PK study designed to assess the safety, pharmacokinetics, adherence, and acceptability of the dapivirine Varginal Ring, inserted every 4-weeks, and once-daily Truvada tablet used by women from sub-Saharan countries during breastfeeding.

MTN-045 was a cross-sectional study that will utilize questionnaires, including a Discrete-Choice Experiment (DCE) and joint decision task, to assess couples’ preferences related to dual purpose prevent (DPP) products that could be used to prevent unintended pregnancies and HIV infection.

PrEP study long-acting Cabotegravir injectable vs Truvada.

Open Label of Long-Acting Cabotegravir ( CAB LA) in Adolescents.

Qualitative study:
Acceptability of injectable Cabotegravir versus daily oral tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) for PrEP.

This trial is in household contacts (HHC) at high risk for developing multidrug resistant tuberculosis (MDR-TB) which is an infection that does not get better with standard treatment for tuberculosis.

Duration:
60 months

Study Population:
18 years and older adults with pulmonary MDR-TB who has started MDR-TB treatment within the past 90 days, who has one or more household contacts and gives site staff permission to call and visit the household contacts.

Objective:
To compare how safe and effective 26 weeks of Delamanid (DLM), a medicine used to treat TB, is versus 26 weeks of isoniazid (INH), a standard medicine to treat or prevent TB, for preventing infection with TB (latent TB) or confirmed or probable active infection with TB among participants with HIV or an immune system problem not from HIV like cancer, latent TB infection and young children below the age of 5 years.

Principal Investigator:
Dr. Eric Wobudeya

Study Coordinator:
Dr. Hellen Kaganzi

Multi-Center, Randomized, Efficacy Study of COVID-9 mRNA Vaccine in Regions with SARS-CoV-2 Variants of Concern

Duration:
14 months

Study population:
Adults who are living with HIV or have another condition that has been associated with increased risk of developing severe COVID-19 illness. Examples of such conditions include pregnancy, diabetes, obesity, heart or kidney disease, and cancer.

Objectives:
– To know how many doses of vaccine are needed for protection against COVID-19 for adults living with HIV or other health conditions that may put them at risk for severe COVID-19.
– To know if people who have already had COVID-19 (and likely have some immunity) need as many vaccine doses as other people to obtain strong protection from reinfection.

Principal Investigator:
Dr. Deo Wabwire

Study Coordinator:
Dr. Joel Maena

Phase 3, SARS-CoV-2 VAT00008 Sanofi A parallel-group, Phase III, multi-stage, modified double-blind, multiarmed study to assess the efficacy, safety, and immunogenicity of two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (monovalent and bivalent) for prevention against COVID-19 in adults 18 years of age and older.

Duration:
1st July 21-30th April 23

Study population:
Adults 18 years of age and older.

Principal Investigator:
Dr. Deo Wabwire

Study Coordinator:
Dr. Joel Maena

The PROMOTE study aimed to measure long-term antiretroviral treatment (ART) safety and adherence; compare HIV disease progression; assess subsequent adverse pregnancy outcomes; evaluate effect of ART exposure on growth and development in HIV-exposed uninfected children; and assess long-term survival of mothers and children.

Site Investigator:
Dr. Lillian Wambuzi

Study Coodinator:
Dr. Patience Atuhaire

PROMOTing Adherence to life-long ART
Cross-cultural translation, adaptation and validation of the AIDS Clinical Trials Group (ACTG) adherence questionnaire and evaluation of two modes of delivery in Uganda; a sub-study nested within the PROMOTE longitudinal cohort study

Re-calibration of quantitative and contextual factors to predict child cognitive deficits in HIV exposed children in the PROMISE/PROMOTE study cohorts

Incidence and risk factors for COVID-19 amongst pregnant and lactating women and their infants in Uganda

Duration:
5th July 2021 – 4th July 2022

Study Population:
Women and Infants

Principal Investigator:
Dr. Kirsty Le Doare

Primary goal of the project is to determine the prevalence of Covid-19 antibody in HIV-infected women and their children and correlate with maternal and pediatric demographics and outcomes.

Duration:
Feb 2022 – May 2022

Study Population:
Women and Infants

Principal Investigator:
Dr. Lillian Wambuzi

A randomised trial of dolutegravir (DTG)-based antiretroviral therapy vs. standard of care (SOC) in children with HIV infection starting first-line or switching to second-line ART.

Duration:
9th October 2019-31st December 2023

Investigator of Record:
Dr. Grace Ahimbisibwe

This is a substudy of ODYSSEY being conducted in Uganda, UK, Zimbabwe and South Africa to look at the involvement of young people in Clinical Trials.

Study Population:
Young people

Investigator of Record:
Dr. Grace Ahimbisibwe

Objective
Deciphering Molecular Mechanisms of HIV Latency Reversal in Perinatal Infections with Single Cell Transcriptomics

Duration:
1st September 2020- 3rd August 2025

Study Population:
Infants

Principal Investigator:
Dr. Linda Barlow- Mosha

Objective
A randomised non-inferiority trial with nested PK to assess DTG/3TC fixed dose formulations for the maintenance of virological suppression in children with HIV infection aged 2 to <15 years old

Duration:
29th November 2021- 28th November 2025

Study Population:
Children (2-15yrs)

Principal Investigator:
Dr. Philippa Musoke

Test the efficacy and safety of once-a-month Islatravir drug on high risk Cis-gender women in Sub-Saharan Africa Primary target audience: HIV negative at high risk Cisgender women, 16-45 years old Focus: The safety and efficacy of once a month HIV prevention treatment drug called Islatravir

Duration:
3 years

Objective:
IMPOWER 22 is studying a new monthly PrEP pill called islatravir—a small, powerful pill that could make protection against HIV much simpler. It looks very promising based on animal studies and is safe and well-tolerated in human studies. The next step is to see if it prevents HIV infection in humans. The IMPOWER 22 study will compare the efficacy and safety of monthly islatravir to daily emtricitabine/tenofovir among cisgender women.

Principal Investigator:
Dr. Brenda Gati

Study Coordinator:
Dr. Enid Kabugho

Official Title: Using Recency Assays to estimate incident HIV infections among Adolescent Girls and Young Women in Hoima and Mityana/Mubende Districts, Uganda

Duration:
4 month

Study Population:
Adolescent girls and young women aged 16-25 years who are at risk of HIV especially those employed in the entertainment industry or at fishing sites, working in commercial sex parlors or on streets and those who identify themselves as commercial sex workers.

Principal Investigator:
Dr. Flavia Matovu Kiweewa

Study Coordinator:
Dr. Zubair Lukyamuzi

Title:
A Phase 3, Double-Blinded, Multicenter, Randomized Study to Evaluate Safety and Efficacy of Twice Yearly Long- Acting Subcutaneous Lenacapavir, and Daily Oral Emitricitabine / Tenofovir Alafenamide for Pre-Exposure Prophylaxis in Adolescent Girls and Young Women at Risk of HIV Infection.

Study Population:
Adolescent girls and young women

Duration:
6 years

Objective:
Project activities aimed at evaluating the efficacy of Lenacapavir (LEN) and emtricitabine/tenofovir alafenamide (F/TAF) in preventing the risk of HIV infection relative to the background HIV incidence in adolescent girls and young women

Principal Investigator :
Dr. Flavia Matovu Kiweewa

Study Coordinator:
Dr. Edrine Kalule

Reaching out to children infected and affected with HIV through their communities.

Duration:
1st July 2019- 30th June 2022

Principal Investigator :
Juliane Etima

Adapting the STARx Transition Readiness Questionaire for Uganda Young People Living with HIV/ AIDs (PLHIV) and their Parents

Duration:
1st August 2020-31st December 2022

Principal Investigator :
Dr. Linda Barlow- Mosha

Bone Mineral Density in a Cohort of Young Adult Women Using Depo-Provera and Tenofovir, Kampala, Uganda.

Duration:
5 years

Study Population:
HIV infected and un-infected women aged 18-35 years attending the public and non for profit non governmental health facilities.

Objectives:
– To determine the combined effect of HIV, DMPA, and TDF initiation on BMD.
– To determine the effect of TDF initiation on BMD among DMPA users.
– To determine whether BMD loss with TDF ART initiation over a 2 year follow up period is greater with DMPA use.

Principal Investigator:
Dr. Flavia Matovu Kiweewa

Study Coordinator:
Esther Isingel

Official Title: Phase IV Open-Label Trial to Assess Bone Mineral Density in a Cohort of African Women on Depo-provera and Tenofovir Disoproxil Fumurate Switched to Tenofovir Alafenamide Fumarate Based Anti-Retroviral Therapy

Duration: 3rd December 2019- 6th June 2023

Objective:
The primarily objective of this study is to assess the effect of switching from Tenofovir Disoproxil Fumurate (TDF) to TAF based ART on bone mass and turnover among women on DMPA for contraception. HIV virologically suppressed women on DMPA will be switched from their TDF based regimen to Bictergravir /Emtricitabine / Tenofovir alafenamide (B/F/TAF; Biktarvy®) in a randomized fashion. HIV infected women on TDF and non-hormonal contraception will be switched to Biktarvy®).

Study population:
20 – 40 year old HIV-infected non pregnant women

Principal Investigator:
Dr. Flavia Matvovu Kiweewa

Study Coordinator:
Esther Isingel

Determining Bone Loss and Bone Mineral Density Recovery Following Repeat Pregnancy/Lactation Among HIV women of ART an R01 study

Principal Investigator:
Dr. Flavia Matovu Kiweewa

Study Coordinator:
Dr Patience Atuhaire

Evaluation of pelvic floor disorders in parous Ugandan women

Duration:
1st February 2022 -31st July 2022

Principal Investigator:
Dr. Flavia Matovu Kiweewa

Official Title:
Developmental, Neuropsychological and Physical Growth Outcomes among HIV Exposed Uninfected Infants who are exposed to antiretroviral drugs

Duration:
5 years

Population:
1200 HIV exposed uninfected (HEU) children in Uganda and Malawi. 600 at MUJHU

Objective:
To evaluate whether prolonged antiretroviral (ARV) exposure among HEU infants in Malawi and Uganda will be associated with any negative late developmental, neuropsychological, neurologic, physical growth or hematologic consequences

Study Population:
HIV Exposed Uninfected, HUU Unexposed Uninfected children at least 5 yrs of age and older from the PROMISE ND study

Principal Investigator:
Dr. Lillian Wambuzi Ogwang

Study Coordinator:
Mai Nakitende

Official Title: Culture-Specific Neurodevelopmental Assessment of HIV-Affected Children

Duration: 5 year

Study Population: 600 children in Malawi and Uganda. At MU-JHU, 60 HIV infected (HIV+) 120 HIV exposed uninfected 120 HIV (HEU) unexposed (HUU) children.

Main Objective:
To adapt and validate Brain Powered Games (BPG), a computerized cognitive rehabilitation therapy (CCRT) program as a neurocognitive assessment for Sub-Saharan African school-age children suffering from neurological insults such as neurotropic infections

Principal Investigator:
Dr. Lillian Wambuzi Ogwang

Study Coordinator:
Monica Okumbe Lyagoba

SHINE Trial is the first Phase III paediatric RCT to evaluate whether the standard 6 months of treatment can be reduced to 4 months in children with smear-negative non-severe (minimal) TB

Official Title: A phase III randomised open trial comparing 4 vs 6 months treatment in children (+/- HIV) with smear-negative non-severe TB in Africa and India

Study Population:
• Age 0-16 years, weight ≥ 3kg
• No known drug resistance
• Clinical decision to treat with 1st line Rx
• Symptomatic but non-severe TB
• Smear-negative on respiratory samples
• GeneXpert positive allowed
• Not treated for TB in previous 2 years
• Known HIV infection status

Coordinator Investigator:
Dr. Eric Wobudeya

Study Coordinator:
Dr. Gerald Bright Businge

Evaluation of an early tuberculosis detection strategy in children with severe pneumonia. Validation of diagnostic tools and algorithms in HIV-infected and severely malnourished children with presumptive tuberculosis.

Study Population:
Children aged below 15 years seeking care at the district hospital and primary health care centres of selected districts.

Duration:
2019-2022

Objectives:
1. To assess the impact on childhood TB case detection of decentralizing an innovative childhood TB diagnostic approach
2. To compare the efficiency, feasibility and acceptability of two decentralization strategies

Coordinator Investigator:
Dr. Eric Wobudeya

Study Coordinator:
Dr. Gerald Bright Businge

RCT of 6-month intensified anti-TB treatment versus 12-month WHO standard anti-TB treatment, for children with TB Meningitis (TBM) (Global Health Trials Team)

Objectives:
his trial aims to answer two questions. Firstly, for children presenting with TBM (a form of tuberculosis that affects the lining of the brain) who are given a shorter and more intensified treatment for their TBM, is this treatment as effective as the standard treatment in preventing TBM-related deaths?
Secondly, if in addition to the anti-TB treatment, the children are given aspirin for the first 2 months after diagnosis, does this prevent long-term neurological disability in these children?

Duration:
1st October 2018 – 30th September 2022

Study Population:
Children under 15 years and over 28 days of age with TBM disease (a form of tuberculosis that affects the lining of the brain), with or without HIV infection

Coordinating Investigator:
Dr. Eric Wobudeya

Study Coordinator:
Dr Gerald Bright Businge

Building the foundations for improving diagnosis of TB meningitis in children

Duration:
14th February 2022-13th February 2023

Study Population:
Children

Investigators:
Dr. Sabrina Kitaka
Dr. Eric Wobudeya

Hospital-based birth defects surveillance in Kampala, Uganda. to determine the prevalence of Birth defects (CDC); the incidence of birth defects in a cohort of over 200,000 deliveries; associated risk factors including antiretroviral drugs; Association of Neural tube defects and folate deficiency; Zika virus and other congenital viral infections.

Duration:
11 years

Study population:
All birth in Kawempe, Mengo, Nsambya and Lubaga. Estimated 528,000

Main Objectives:
– Establish a surveillance system for major external birth defects among all live and still births delivered or registered as being born at four major hospitals in Kampala.
– Describe the maternal risk factors associated with major external birth defects among newborns.
– To explore parents/caregivers, health workers and community health extension workers perceptions, experiences and meanings attached to major external birth defects

Principal Investigator:
Prof. Philippa Musoke

Co-principal Investigator:
Dr. Linda Barlow-Mosha

Program Manager:
Dr. Daniel Mumpe Mwanje

A Randomized Trial to Evaluate Mirasol Whole Blood Pathogen Reduction Technology System to Reduce Malaria and Other Transfusion Transmitted Infections (US Department of Defense).

Duration:
3.5 years

Population:
Patients who weigh more than 30kg, who require a blood transfusion and are willing to participate in the study and fulfill other eligibility criteria

Main Objectives:
To determine the effectiveness of Mirasol-treated fresh whole blood for preventing transmission of transfusion transmitted infections i.e. malaria, HIV, HBV, HCV, HEV, HHV-8, and bacteria.

Principal Investigator:
Dr. Irene Lubega

Co-investigator:
Dr. Ronnie Kasirye

Coordinator:
Dr. Hellen Musana

Multi-centre observational study (Neo-Obs-001) to collect clinical and microbiological information on presumed and confirmed serious bacterial infections in neonates

Study Population:
Infants

Principal Investigator:
Dr. Philippa Musoke

Seroepidemiology of Maternally derived antibody against Group B Streptococcus (GBS) in preparation for GBS vaccine studies

The immunogenicity of combined pertussis-containing vaccine (Tdap) for HIV infected pregnant women and their newborns-A Randomized Clinical Trial.

Study Population:
Infants

Program Manager:
Dr. Mary Kyohere

Prevention of invasive Group B Streptococcus disease in young infants: a pathway for the evaluation & licensure of an investigational maternal GBS vaccine

Duration:
01/09/19-30/09/24

Study Population:
Mother and Infants

Principal Investigator:
Dr. Kirsty Le Doare

Program Manger:
Dr. Robert Mboizi

Our project aimed to increase awareness of maternal immunisation in the ten parishes surrounding a maternal health specialty, Kawempe National Referral Hospital, in Uganda. Our primary target audience were pregnant women and women of child-bearing age and their influencers. The focus was on community education emphasizing the benefits and dispelling myths and misconceptions of maternal vaccines; using these to trace and refer women who default on the maternal immunisation schedule. Using mixed methods of health promotion, the project leveraged various media channels including mobile films at community level, radio messaging, and women influencers’ support groups.

Project Lead:
Dr. Mary Kyohere

Duration:
6 months