Tuberculosis treatment in hospitalized HIV patients with severe immune suppression
Tuberculosis (TB) remains the leading cause of death among PLWH, accounting for around one in three AIDS-related deaths. In the severely immunocompromised patients, TB incidence is high and represents the most frequent cause of hospitalization and death. Mortality is particularly high among those patients who start TB treatment while being hospitalized, ranging from 6% to 32%. Disseminated TB remains a life-threatening condition for this population. The objective of the DATURA project is to estimate the impact of an intensified initial phase of tuberculosis (TB) treatment on mortality at 48 weeks among HIV-infected adults and adolescents hospitalized for TB with CD4 ≤ 100 cells/μL in comparison with standard TB regimen. This study is funded by the French Agency for Research on AIDS and Viral Hepatitis and Emerging Infectious diseases.
Childhood tuberculosis diagnostic innovative approach
Most of the children with TB are not diagnosed and do not benefit from appropriate treatment due to the poor access to childhood TB diagnosis at low level of health care facility in most high-burden countries. Effective, affordable and easy-to-use diagnostic and sample collection tools are still lacking together with qualified human resources. In addition there is no systematic detection of TB in highly vulnerable children (severely malnourished children HIV-infected children and children with severe pneumonia). The TB speed project aimed to contribute to the reduction in childhood mortality from tuberculosis by delivering an available, feasible, cost-effective, and decentralized childhood tuberculosis diagnostic approach to enhance case-finding and access to treatment. The project focused on two major axes: 1) increasing access to diagnosis through decentralized pediatric TB diagnosis at district and sub-district levels, and 2) increasing systematic and rapid TB detection in vulnerable children, i.e. those with severe pneumonia, HIV infection and/or with SAM (Severe Acute Malnutrition). The project was deployed between 2017 and 2022 in seven limited-resource countries with a high incidence of tuberculosis: Cambodia, Cameroon, Côte d’Ivoire, Mozambique, Sierra Leone, Uganda and Zambia. This project was funded by Unitaid and L’Initiative.
Tuberculosis preventive therapy among People living with HIV
Despite strong progress, Cambodia continues to face serious challenges detecting and preventing tuberculosis (TB) cases, particularly among people living with HIV (PLHIV). Cambodia guidelines call for universal coverage of Tuberculosis Prevention Therapy (TPT) among PLHIV; however, in 2017, TPT coverage among newly initiating ART patients was 21%, and less than 30% of the entire ART cohort had ever received a course of IPT.
The OPTICAM study proposed to understand and address the full range of system- and provider patient-side barriers to Tuberculosis Prevention Therapy (TPT) and to assess the impact on initiation of TPT in PLHIV of a comprehensive package including shorten therapy. Specifically, the objectives were to: 1) Design a comprehensive intervention to improve uptake of TPT; 2) Sensitize providers on the normative guidance on TPT for PLHIV; 3) Develop and test the impact and cost-effectiveness of a comprehensive intervention, including an optimized screening algorithm, on uptake of TPT; and 4) Assess the impact of 1HP versus 3HP use in the TPT uptake and completion as part of a comprehensive intervention. This study was funded by l’Initiative.
Prevention of HBV mother to child transmission
Chronic Hepatitis B affects 350 million individuals in the world. The maternal-fetal transmission of HBV infection is the cause of most chronic Hepatitis B in countries highly endemic for HBV since about 50% of the 350 million chronic Hepatitis B carriers acquired infection perinatally. Women of childbearing age with chronic hepatitis B are the most important reservoir for transmission of HBV, particularly in Southeast Asia. Their follow-up is therefore a key opportunity to interrupt perinatal transmission of HBV chain. Mother-to-child transmission (MTCT) of Hepatitis B virus (HBV) is based on administration of vaccine and immunoglobulins (HBIg) to newborns at birth and maternal antiviral prophylaxis for those with an HBV-DNA viral load of at 5·3 log10 IU/mL or more. In fact, many low-income and middle-income countries face difficulty in accessing HBIg and HBV-DNA quantification. The aim of the TA-PROHM study was to evaluate the effectiveness of an HBIg-free strategy to prevent MTCT of HBV. An interventional strategy using rapid test screening and tenofovir treatment for HBV infected pregnant women to prevent HBV mother to child transmission was implemented in Cambodia. This study was funded by the French Agency for Research on AIDS and Viral Hepatitis and Emerging Infectious diseases.
Evaluation of the effectiveness of HCV treatment for children and adolescents with active HCV infection
The prevalence and burden of HCV infection in children and adolescents are less well understood than in adults. The transmission from mother to child is the main route of acquisition of HCV mono-infection and of HCV/HIV coinfection. In addition, in low-income settings, exposure to unsafe medical interventions also contributes to transmission and intra-familial horizontal transmission of HCV has been described. After acquisition of HCV, between 25% and 40% of infected children spontaneously clear the virus in the first 4 years of life. For the others, advanced liver diseases with cirrhosis and liver cancer could occur and the proportion of patients with bridging fibrosis/cirrhosis, evaluated by liver biopsies, was reported to increase from 11% to 20% in a median time of 5.8 years. In June 2022 WHO has revised the recommendations for DAA regimen in children and adolescents. WHO recommended to use of pan-genotypic DAA regimens for all adults, adolescents and children with chronic hepatitis C infection aged 3 years and above, regardless of stage of disease.
The HEPEDIAC study will evaluate the effectiveness of sofosbuvir/daclatasvir combination for children aged 6 years old and adolescents with active HCV infection in Cambodia. This study is funded by the French Agency for Research on AIDS and Viral Hepatitis and Emerging Infectious diseases.