This is a phase II, randomized, double-blind, placebo-controlled clinical trial to assess the safety, tolerability, and efficacy of 24 weeks of treatment with Selgantolimod (SLGN). Intensive PK sampling will be conducted in the first 12 participants who enroll into the study.

The hypothesis is that administration of the oral toll-like receptor (TLR) 8 agonist SLGN will be safe and well-tolerated in participants with both CHB and HIV on suppressive antiviral therapy for both viruses. Therefore, this study will evaluate 3 mg SLGN dosing among virally suppressed individuals with both HIV and CHB.

Expected Impact:  To inform global CHB treatment guidelines, where we have SLGN approved for treatment of chronic hepatitis B among HIV-infected individuals.

In this study, the bactericidal activity and safety of 3 doses of TBAJ876 (25 mg, 50 mg, and 100 mg) in combination with Pretomanid 200 mg and linezolid 600 mg will be compared to the standard of care (SOC) 2HRZE, after 8 weeks of treatment to determine the optimal dose of TBAJ876 to carry forward in subsequent phases of development. The trial will also examine the bactericidal activity of B-Pa-L compared to 2HRZE and TBAJ876-Pa-L over 8 weeks and examine the efficacy and safety of the 26-week B-Pa-L regimen compared with the SOC (2HRZE/4HR) in participants with DS-TB. These data will provide insight into the optimal duration of treatment required for the TBAJ876-Pa-L regimens, and support the planning for a future phase 3 trial.

Expected impact: This trial may lead to eventual registration of a new second generation diarylquinoline, as part of a regimen, with the potential of improved potency/efficacy compared to the currently approved diarylquinoline, reduced treatment duration, potential to treat Bedaquiline-resistant MTB infections, and improved tolerability

Recruitment rate: 140%

Retention rate: 90.5%

HIV-infected children face unique challenges, such as; perinatal transmission of drug resistant HIV virus, limited safety data, impact of ARVs on their grown and development, need for different formulations and doses as they grow, and ease to transition to adult formulations. These issues challenge the development of a single fixed dose combination (FDC).

The UNIVERSAL 1 study aims to assess the short-term pharmacokinetics, safety and efficacy of DTG and FTC/TAF dispersible formulations with specific calculated doses are within the ranges previously reported for adults and children, to allow for universal dosing for a pediatric FDC administered to HIV-infected children, aged 28days to ≤10years, weighing ≥3kg to <25kg.

Expected impact: To have one safe and efficacious FDC first-line ART regimen, that can be used for children across the different WHO weight bands, and ages, and allow for easy transition to adult ART regimens.

Standard detection methods for viral RNA in patients include RNA purification, reverse transcription and quantitative PCR (RT-qPCR). These processes are time consuming, require multiple biochemical reagents, lab-grade instruments and trained professionals. Further, most qRT-PCR assays are inherently complex and require a time-consuming multi-step RNA extraction prior to nucleic acid amplification and achieve desired detection performance. Such assays also require real-time fluorescence detection equipment that is typically limited to 96 samples per instrument run.

The AirJump sample preparation will be used for extraction of SAR-Cov2-RNA. The AirJump performs efficiently, with high analyte yield, high purity, no cross contamination, rapid time-to-isolation, and excellent reproducibility.

This study aims to establish a proof of concept and carry out validation of RARA assay in the laboratory before the field evaluation in testing of SARS-CoV-2. The inherent characteristics of this assay will be evaluated with regard to accuracy (diagnostic sensitivity, diagnostic specificity), Precision (reproducibility), Limit of detection (LOD), Predictive value (negative and positive), and Assay Efficiency, if this validation is successful.

Expected impact: An fordable, accurate, highly sensitive point-of-care test for SARS-Cov2 virus.

There is need for anti-malarial combination therapy (ACT) comprising of at least one partner drug with a new mechanism of action to reduce developing resistance.

The purpose of this study is to evaluate the parasiticidal effects and potential for cure with different anti-malarial agents administered as monotherapy and/or in combination with other anti-malarial agents in adults, children, adolescents, with uncomplicated P. falciparum malaria

Expected impact: Offer an option of anti-malarial treatment with a new mechanism of action, and an alternative drug for patients infected with resistant parasites.

This study enables continued access to Rilpivirine (RPV), for the evaluation of the long-term safety and tolerability of RPV in combination with other optimized background ARVs, in HIV-infected children aged 2years -<12years who were virally suppressed at enrolment.

This is an open-label single-arm study, that will provide continued access to study drug to participants who completed their participation in parent studies sponsored by Gilead Sciences US, which include; GS-US-292-0106, GS-US-380-1474, GS-US-311-1269, GS-US-216-0128, or CO-US-380-5578.

Bictegravir/Emtricitabine/Tenofovir alafenamide (B/F/TAF) will be provided for participants rolling-over from GS-US-380-1474- or CO-US-380-5578. Emtricitabine/Tenofovir Alafenamide (F/TAF) will be provided by Gilead Sciences for participants rolling-over from GS-US-311-1269.

Expected impact: Continued access to efficacious ART before access is possible through national local supply chain systems.

The aim was to test the safety, effectiveness, and pharmacokinetics of a new HIV medication, GS-9883. Participants received the new medication for 48 weeks.

Tenofovir disoproxil fumarate (TDF) is a preferred NRTI among recommended regimens for treatment-naive HIV-infected adults and adolescents, but is associated with nephrotoxicity and reduced bone mineral density. Lifelong antiretroviral treatment and the increasing comorbidities being recognized and treated in HIV-infected patients creates an urgent need to improve the safety profile of regimens that most effectively suppress HIV replication.

Genvoya (E/C/F/TAF) was approved in adults and pediatric patients 12 years of age and older in the US and EU in 2016 and approved in 2017 for use in pediatric patients 6 to < 12 year of age weighing ≥ 25 kg. HIV-infected children ages ≥ 2 years of age will benefit from the availability of an age-appropriate formulation containing TAF, which has the potential for an improved renal and bone safety profile relative to TDF, an important consideration for a population in which peak bone mass has not yet been achieved and for whom HIV treatment is anticipated to be life-long.

The objective of this study was to characterize the pharmacokinetics (PK), and confirm the dose of E/C/F/TAF and to evaluate the safety, tolerability and antiviral activity of E/C/F/TAF as an STR in treatment-naive HIV-1 infected adolescents 12 to less than 18 years of age and in virologically suppressed HIV-1 infected children 2 to < 12 years of age.

Expected impact: Provide data on plasma exposures in the pediatric population that are comparable to those associated with safety (less effect on bone mineral density and renal function), and efficacy in adults.

This study builds on research conducted in the early 2000s that examined the relationship between hormonal contraceptive use, genital tract microbiome diversity and HIV seroconversion. Archived biological samples from the original cohorts were securely stored and later retrieved in 2024. The participants vaginal swabs were processed and analyzed for genital tract microbiome shedding. Furthermore, contemporary molecular methods, including nucleic acid extraction, amplification, and sequencing, to generate HIV genotypic resistance profiles. The project leverages historical cohorts to address current research questions on HIV drug resistance using modern laboratory technologies.

Expected impact: Evidence on HIV genotypic resistance sequences derived from archived samples, comparative analyses linking historical cohort data with current resistance profiles, and characterization of genital tract microbiome

This collaborative research project encompasses several studies focused on HIV drug resistance among patients receiving antiretroviral therapy. The work involves genotypic resistance testing to identify mutations associated with resistance to different classes of antiretroviral drugs targeting the integrase gene among patients with DTG failure. The findings support treatment optimization, surveillance of resistance patterns, and evidence-based policy formulation.

Expected impact:  Evidence to inform HIV treatment guidelines for individuals with DTG resistance.

This project focused on the detection and monitoring of SARS-CoV-2 in wastewater as a public health surveillance tool. The study aimed to assess the feasibility and effectiveness of wastewater-based epidemiology for tracking COVID-19 trends at community level, complementing clinical surveillance systems. Laboratory analysis included molecular detection techniques to identify viral RNA in wastewater samples. The project was successfully completed in 2023.

Expected impact: Surveillance data on SARS-CoV-2 presence in wastewater, and contribution to public health surveillance strategies

This study is a Phase III, double-blind, placebo-controlled, multi-arm platform study that will enroll participants from Brasil, Canada, Italy, Uganda, Zambia, and the United States. The first phase, involving 348 participants, will investigate two repurposed drugs over a 3-month period, each paired with its own placebo, followed by an interim analysis. After completing the 3-month treatment, the original 348 participants will be monitored for an additional 3 months for symptom rebound and safety. The second phase, guided by the results of the first phase, will be followed by a final analysis. In this phase, the study may continue with one or both repurposed drugs, combine one with an add-on repurposed drug, or introduce completely new repurposed drug(s).

Expected Impact: Identify safe and effective drugs for treatment of post-COVID disease.

This study aims to compare the total white blood cell counts and differential white blood cell subtypes obtained using the Non-Invasive White Cell Monitoring prototype with those obtained through conventional complete blood count (CBC testing via vein puncture in healthy volunteers.  The NICEM device or system can be operated by personnel with minimal training, enabling BC determinations at a fraction of the cost of conventional testing, as well as providing testing in settings where CBC testing was either very difficult to obtain or was not at all obtainable. This will address important equity issues in care provision.  Currently, there are many patients in rural, remote, and resource-limited settings who have suboptimal access to care, in part due to a lack of functional laboratory or other support services. This proposal will, in effect, bring the laboratory to the bedside, enabling health care providers to improve the range and quality of care provided. We will use primary components that can be created at low cost and in resource-constrained settings.

The study objective is to compare the total white blood counts and differential white blood cell subtypes obtained by the Non-Invasive White Cell Monitoring prototype with conventional CBC testing using vein puncture in healthy volunteers.

Expected impact: The NICEM devise is expected to ease lab workload and reduce the need for phlebotomy, support faster clinical decisions at point-of-care, avoid pain in children, promote non-invasive testing and patient monitoring of blood composition, and improve access to care in resource-limited settings.

Crizanlizumab is a potent and selective IgG2 (immunoglobulin G2) kappa humanized monoclonal antibody that binds to human P-selectin with high affinity, blocking its interaction with its ligands, including P-selectin glycoprotein ligand 1 (PSGL-1). Extensive pre-clinical data have established P-selectin as a key mediator of VOC in SCD (Matsui et al 2001) and suggest that blockade of P-selectin could eliminate or reduce VOC.

The objective of this study is to assess the efficacy and safety of crizanlizumab (5 mg/kg) versus placebo, with or without hydroxyurea (HU)/hydroxycarbamide (HC), on VOC rate in Sickle Cell Disease (SCD) patients aged 12 years and older who experience frequent vaso-occlusive crises (VOCs).

SPARKLE study, is a new phase III study developed to confirm the efficacy of crizanlizumab demonstrated in the SUSTAIN study and other open label studies.

Expected impact: Crizanlizumab as an effective treatment option for SCD, with reduction in frequency of VOC, and improvement in patients’ quality of life and life expectancy.

Amendment: The role of Trained Immunity and Mitochondrial dysfunction on INnate immunity in children and adolescents aGing with PHIV (TIMING-PHIV)’

Description:

The impact of inflammation on non-AIDS co-morbidities in children may be greater in Sub-Saharan Africa due to co-infections, nutritional status variations and other factors.

This TIMING study will measure innate immune profiles (monocytes and natural killer cells), in adolescents with and without HIV in Uganda and USA. The study will also identify the role of trained immunity in innate immune modulation in adolescents with and without HIV.

Expected impact: Identification of targets for novel interventions to decrease inflammatory consequences and improve the children’s quality of life.

The combination of anti-sickling effects, decreased haemolysis and improved red blood cell (RBC) membrane integrity due to etavopivat treatment is proposed to improve RBC health and reduce the onset and complications of VOCs and, in parallel, address the chronic anaemia of SCD. Both chronic anaemia and VOCs contribute to end organ damage and reduced QOL that is common place among patients with SCD.

The objective of this study is to confirm efficacy and safety of etavopivat (compared to placebo) on annualised VOC rates, measures of end organ damage, functional exercise capacity, as measured by the 6-minute walk test (6MWT), and quality of life measures (QOL) (including fatigue) in adolescents and adults with SCD enrolled in the study. Additional Patient Reported Outcome (PRO) QOL measures, including pain, emotional and functional impact, will also be used to confirm efficacy of etavopivat in adolescents and adults with SCD. The aim is to demonstrate superiority of treatment with etavopivat versus placebo in adolescents and adults (age ≥12years) with SCD.

Expected impact: To have Etavopivat as an effective treatment option for SCD, with reduction in frequency of VOC, and improvement in patients’ quality of life and life expectancy.

Despite these recent advances, there remains a pressing need to develop new and highly effective regimens for the treatment of TB that have broad activity (capable of treating both rifampicin- susceptible and resistant organisms) and that may permit a significant reduction in the duration of treatment (e.g., to ≤ 4 months).

This randomized, open-label, multi-center, seamless Phase 2B (regimen selection) and 2C(treatment duration), multi-arm, multi-stage, Platform clinical Trial, evaluates multiple regimens and  durations  of  treatment  in  pulmonary tuberculosis (TB).

The main aim is to identify novel drug regimen(s) with acceptable safety profile, non-inferior efficacy and shortened treatment duration compared to the standard-of-care 24-week HRZE regimen that could be used to treat people with rifampicin susceptible and rifampicin resistant TB.

In stage 1 the new drug combinations will first be compared to the established standard-of-care (SOC) first-line drug combination. Each new drug combination will be taken for a period of 4 months and the established treatment combination will be taken for a usual period of 6 months. The drug combinations that look most promising in the “phase 2B trial” will then advance to the second stage for testing in a new group of people with drug-susceptible TB.

The adaptive trial approach used in the PARADIGM4TB (UNITE4TB-01) trial is new and innovative. Integrating 2 stages, the phase 2B and phase 2C, within the same trial, will minimise the long delays arising from testing combinations in separate trials.

Expected impact: Safe and efficacious new TB treatment options with shorter duration for drug-susceptible and drug-resistant TB.

Outpatient Treatment with Anti-Coronavirus Immunoglobulin (OTAC) (INSIGHT 012)

Coronavirus disease 2019 (COVID-19) is a predominantly respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and causes substantial morbidity and mortality. It is plausible that initiation of therapy early in the course of COVID-19, and before overt clinical symptoms and signs of pneumonia requiring hospitalization have developed, may reduce the subsequent risk of disease progression to pneumonia with hypoxia, hospitalization and death.

Therefore, this trial evaluates a passive immunotherapy strategy in hyperimmune intravenous immunoglobulin (hIVIG) among participants with early SARS-CoV-2 infection, given in addition to current standard of care (SOC) treatment(s) as available and specified by established national and international guidelines (e.g., the National Institutes of Health (NIH) COVID-19 Treatment Guidelines, or the World Health Organization (WHO) Therapeutics and COVID-19 Guidelines).

The primary objective of the trial is to compare the safety and efficacy of a single infusion of anti-COVID-19 hIVIG versus placebo among adults (ages ≥18years, ≥55years), with recently diagnosed SARS-CoV-2 infection who do not require hospitalization.

Expected impact: The hIVIG may be an efficacious SARS-CoV-2 agent, with greater neutralizing potency compared to convalescent plasma, reducing the risk of disease progression to pneumonia with hypoxia, hospitalization and death.

Preliminary data suggests a probable effect of HIV on myocardial fibrosis and steatosis in women, with inflammation being a key driver of fibrosis and metabolic dysfunction.

The primary objective of this study is to characterize myocardial fibrosis burden and identify novel infectious/immunologic predictors of progression among women with HIV on ART, in Sub-Saharan Africa. The study also aims to quantify myocardial steatosis burden and identify predictors of progression among women with HIV on ART, in Sub-Saharan Africa.

Despite the availability of multiple public health interventions, approximately 608,000 malaria deaths were recorded in 2022, with the majority of these deaths occurring in children under 5 years of age. Reducing the global malaria burden will require the development and implementation of new prevention strategies, including the use of vaccines, expanded monthly chemoprevention, and antibody-based prophylaxis. Multiple monoclonal antibodies (mAbs), including MAM01, that target conserved sequences within the circumsporozoite protein (CSP) for P. falciparum (Pf) infection prevention are in early development.

MAM01 is an engineered version of a human IgG1 (Immunoglobulin G1 subclass) mAb generated following vaccination with RTS,S/AS01 vaccine.

This age de-escalation and dose escalation study, aims to assess the safety and tolerability of intravenous (IV), subcutaneous (SC) and intramuscular (IM) injection of MAM01 in African adults (18-55years), young children (2-<5years, and 12months to <24months), and infants (3 to <12months) in a setting of prerrenial malaria transmission.

Expected impact: The results will help determine the future potential for mAbs as a new class of malaria prevention tools in moderate-high perennial transmission settings.

Improving HIV Outcomes in Africa with Long-acting Antiretrovirals

Long-acting (LA) injectable therapy for the treatment of Human Immunodeficiency Virus (HIV)-1 infection offers a reduced dosing frequency and an additional option to the currently available 2 or three-drug oral combinations. A parenteral LA formulation of rilpivirine (RPV) (Janssen) for intramuscular (IM) injection in combination with ViiV Healthcare’s parenteral LA formulation of the integrase inhibitor cabotegravir (CAB) for IM injection may offer improved adherence and treatment satisfaction in virologically suppressed patients.

The IMPALA study is a phase 3b randomised, multicentre, open-label study evaluating the effectiveness of switching to two-monthly long-acting injectable cabotegravir and rilpivirine from first-line oral antiretroviral therapy in HIV-1 positive virologically suppressed adults with a history of, or at risk of, sub-optimal HIV control in sub-Saharan Africa.

The primary objective of the study was to demonstrate the non-inferior efficacy of switching to every 2 months (Q2M) intramuscular (IM) injection of cabotegravir (CAB) long-acting (LA) plus Rilpivirine (RPV) LA compared with continuation of daily oral ART over 12 months in people living with HIV-1 (PLHIV1) with a history of, or at risk of, sub-optimal ART adherence or engagement in care.

RESULTS: The 2-monthly injectable cabotegravir + Rilpivirine (CAB/RPV) regimen was non-inferior to daily oral Dolutegravir-based therapy. At week 48, 91% of participants in the injectable arm maintained a viral load below 50 copies/mL, compared to 89% in the oral treatment arm.

Expected impact: The results, alongside similar data from the CARES study, supported WHO’s decision to include this regimen in the updated HIV treatment guidelines. This has emphasized the need to expand access to long-acting injectables for PLHIV in Africa.

Recruitment rate: 100%

Retention rate: 100%

Neurocognitive impairment (NCI) is one of the most prevalent and deleterious complications observed in adolescents and young adults (AYA) with perinatally acquired HIV (PHIV), even despite viral suppression. There are evidence gaps about what drives NCI in virally suppressed people with PHIV greatly limit our ability to develop targeted and tailored interventions for it. Enduring multiple co-occurring adversities (i.e., syndemics) as well as timing, duration and type of ART, may affect the relationships between HIV and immune dysfunction (ID), and thus Neurocognitive impairment (NCI), differently in PHIV vs HHIV, but research has not addressed this.

This study will evaluate the difference in ID and NCI in virally suppressed PHIV and horizontally acquired HIV (HHIV), as well as HIV unexposed uninfected (HUU) AYA (15-25years) old in Uganda controlling for chronic adversities. The study will also evaluate the relations hips between ID and NCI in AYA with all the three groups (PHIV, HHIV, HUU)

Expected impact: Knowledge to foster Ugandan and US capacity to examine ID and NCI across diseases and populations.

Life-long ART presents new challenges of treatment fatigue and long-term toxicities, and the growing population in need of ART pose critical public health questions over the long-term financial sustainability of continued ART scale-up. In response to this, research interest has shifted beyond survival and viral suppression to optimising treatment safety and health-related quality of life, with focus on regimens that are easier to take, offer less risk of toxicity and are more affordable, while remaining highly effective. Dual therapy, using two antiretrovirals instead of three with at least one anchor drug, is one of these approaches for initial and maintenance therapy.

This open-label multicentre randomized non-inferiority trial, compares virological efficacy of two drug ART regimen, Dolutegravir (DTG) and lamivudine (3TC) (known as DTG/3TC), given in comparison with triple-drug standard-of-care (SOC) ART consisting of 2 nucleos(t)ide reverse transcriptase inhibitor (NRTI) and a third (anchor) drug (either an integrase strand transfer inhibitor (INSTI), a protease inhibitor (PI) or a non- nucleoside reverse transcriptase inhibitor (NNRTI).

This study aims to find out whether treating children and young people living with HIV with two anti-HIV medicines, dolutegravir and lamivudine, is safe and as effective as the three-medicine anti-HIV treatments currently used in routine practice.

Expected impact: To have DTG/3TC as a non-inferior ART option for children and adolescents living with HIV, to maintain viral suppression with minimal ART toxicity.

Recruitment rate: 99% (103 of 104)

Retention rate: 100%

This is a global first-in-human randomized Phase I/II clinical study of ITU512, to assess the safety, tolerability, PK, PD and preliminary food effect of ITU512 in adult healthy participants, and safety, tolerability PK, PD, and efficacy of ITU512 in adolescent and adult patients with sickle cell disease (SCD). The study consists of Part 1 which is a first-in human Phase I study in healthy participants, and Part 2 which is a Phase II study in patients with SCD.

While the benefits of ITU512 on HbF induction have been demonstrated in preclinical studies, this will be the first clinical evaluation of the potential therapeutic effect of ITU512 in healthy participants and participants with SCD. The results of the study will be used to inform future development plans for ITU512 in SCD and β-globinopathies.

Expected impact:

ITU512 as a safe and efficacious oral option for SCD treatment. Participants with SCD may derive clinical benefit such as reduction in occurrence of vaso-occlusive crises, as ITU512 induces fetal hemoglobin.

The combination of CAB LA and RPV LA has been shown in clinical trials in virologically suppressed adults living with HIV to be safe, well-tolerated and efficacious as a complete injectable antiretroviral regimen.

The primary objective of this study is to provide continued CAB LA + RPV LA access to participants who were enrolled and treated with CAB LA + RPV LA in the parent studies, and who, at the time of rollover, experience clinical benefit from this treatment, but do not have access to locally available CAB LA + RPV LA to continue treatment.  The parent studies include; IMPAACT 2017 [MOCHA], IMPAACT 2036 [CRAYON], TMC278LAHTX3002 [CARES], and TMC278LAHTX3005 [IMPALA]. The rollover study will be reviewed periodically to evaluate other access options.

The participants receive CAB LA + RPV LA given intramuscularly on a once every 4 weeks (Q4W) or every 8 weeks (Q8W) dosing schedule. The study will also assess the long-term safety and tolerability of CAB LA + RPV LA by evaluating the incidence of serious adverse events (SAEs), pregnancies, adverse events (AEs) leading to discontinuation of CAB LA + RPV LA, and AEs (excluding Grade 1 and Grade 2 injection site reactions) considered to be related to the study intervention.

Expected impact: This study enables continued access to CAB LA + RPV LA and allows for the evaluation of the long-term safety and tolerability of CAB LA + RPV LA.

The CAPRI study will evaluate the reproducibility of Cascade Primed Cells with Apheretic collected Autologous PBMCs in Uganda, and test the effect of the reproduced CAPRI cells on Lung and Cervical cancer cells in vitro.

Adolescents have poorer treatment outcomes including higher loss to follow-up, lower treatment adherence, poorer virological suppression and higher mortality than older people living with HIV. Some of the adherence challenges in adolescents revolve around fear of disclosure associated with carrying/taking medication, HIV-stigma, and the burden of secrecy; this may be particularly difficult at weekends which are times for socialising with friends. Unstable lives, non-conducive to daily medication adherence, and relative lack of power in treatment decision-making also contribute to difficulties with daily-dosing, and may affect virological suppression.

The overarching objective of this trial was to evaluate an innovative and contemporary ART strategy in HIV-infected adolescents to provide choice for young people facing life-long treatment.

The BREATHER PLUS trial evaluated the virological efficacy, safety, acceptability and Quality of Life of DTG-based Short-cycle Therapy (SCT) with weekends off compared with Continuous Therapy (CT) with a DTG-based ART regimen, to optimise treatment for HIV-infected adolescents in sub-Saharan Africa. The backbone drugs will consist of tenofovir either as the TAF or TDF formulations partnered with either 3TC or FTC.

Expected impact: Evidence on efficacy, safety and acceptability of a novel treatment approach (weekends-off) in HIV-infected adolescents in sub-Saharan Africa.

Results: At week 96, a higher rate of viral failure occurred in 10% of the SCT (n=23) vs 5% in the CT arm (n=11); diff 5.1% (99%CI: –0.9 to +11.5). The showed that SCT was not non-inferior. The difference was also 5.1% (95%CI: +0.05 to +9.9), which showed that SCT was actually inferior to CT (p=0.034).

Reduced dosing (SCT) with TLD can not be recommended for adolescents when viral load is only monitored every 6-12 months. Therefore, daily TLD (CT) should continue to be recommended in adolescents living with HIV.

This is a Phase III, open-label, multi-center trial with a cluster-randomized superiority design. The purpose of the study is to compare the efficacy and safety of 26 weeks of Delamanid (DLM) versus 26 weeks of isoniazid (INH) for preventing confirmed or probable active TB during 96 weeks of follow-up among high-risk household contacts (HHCs) of adults with multidrug-resistant tuberculosis (MDR-TB). High-risk HHCs are those with HIV or non-HIV immunosuppression, latent TB infection, and young children below the age of 5 years.
The study tests the hypothesis that treating household contacts (children, adolescents, and adults) of multidrug-resistant tuberculosis (MDR-TB) patients, including those with pre-extensively (pre-XDR) and extensively drug resistant (XDR) TB, who are at high risk of developing TB with delamanid (DLM), will substantially reduce the risk of developing TB compared with treatment with isoniazid (INH) preventive therapy.
Expected impact: To inform global TB prevention guidelines, where we have Delamanid as a safe and effective option for TB preventive treatment.

Recruitment rate: 114%

Retention Rate: 100%

It is a Phase 2/3, Open-Label Study to confirm the dose of elvitegravir/cobicistat/emtricitabin e/tenofoviralafenamide (E/C/F/TAF) single tablet regimen (STR) in HIV-1 infected, antiretroviral (ARV) treatment naive adolescents and evaluate the pharmacokinetics, safety, tolerability, and antiviral activity of E/C/F/TAF STR in HIV-1 infected, ART naive adolescents and virologically suppressed HIV- 1 infected children. Antiviral activity is determined by the achievement of HIV-1 RNA < 50 copies/mL at Weeks 24 and 48