Monitoring the treatment of HIV-infected infants in West Africa
LIH participated to a large phase III clinical trial, the MONOD ANRS 12026 study that was recently completed after having run for over five years. It aimed to improve and simplify the treatment of HIV-infected infants in two sites in West-Africa: Ouagadougou, Burkina Faso and Abidjan, Ivory Coast.
The HIV paediatric epidemic in Africa is still a major public health challenge. According to UNAIDS, the Joint United Nations Programme on HIV/AIDS, 3.2 million children under the age of 15 were living with HIV and 240,000 were newly infected in 2013. The World Health Organisation (WHO) recommended in 2010 to treat all HIV-infected children less than two years of age with antiretroviral drugs.
The MONOD trial aims to evaluate the implementation of early antiretroviral treatment strategies in HIV-infected infants and assess the feasibility and efficacy of simplifying the initial proposed regimen after a successful one year treatment.
In low-income countries, the first line therapy that is recommended for infants is based on a protease inhibitor, a drug named lopinavir/ritonavir. It however presents many challenges as it is more costly than other anti-HIV drugs, requires refrigeration for storage and must be administered twice a day. The MONOD trial assessed the use of an alternative once-daily treatment without protease inhibitor, based on a non-nucleoside reverse transcriptase inhibitor named efavirenz.
Between May 2011 and January 2013, 156 children less than two years old were included in the clinical trial to receive antiretroviral treatment. They first received a treatment based on lopinavir/ritonavir for 12 months, which led to a high viral suppression rate. Then they were split into two groups, one continuing this treatment, the other one getting the alternative efavirenz-based treatment.
When viral suppression was monitored 12 months later, the scientists found that there were no significant differences in adverse events between the two therapies and that the efavirenz-based treatment was not less efficient than the lopinavir/ritonavir- based treatment. Nevertheless the therapy switch can only be recommended if the viral load is closely monitored since drug resistance mutations have already emerged. Thanks to the MONOD trial and another similar HIV trial named NEVEREST-3 conducted in South Africa, a revision of the WHO guidelines for HIV treatment was made in 2016.
The collaborators from Luxembourg in the MONOD trial were Dr Carole Devaux, Principal Investigator of the HIV Clinical and Translational Research group at LIH’s Department of Infection and Immunity, Dr Jean-Claude Schmit, formerly CEO of LIH and now Director of Health at the Ministry of Health, and Dr Vic Arendt from the National Service for Infectious Diseases of the “Centre Hospitalier de Luxembourg”.
‘We were responsible for the quality controls of the biological and virological monitoring of all patients in both sites. We were additionally in charge of performing HIV genotyping and determining the HIV drug resistance status of the patients from Ouagadougou’, states Dr Devaux.
The MONOD ANRS 12026 study was coordinated by Dr Valériane Leroy from the University of Bordeaux, France and supported by European Developing Countries Clinical Trials Partnership (EDCTP), Inserm-ARNS and the Luxembourg National Research Fund (FNR).
Publications resulting from the MONOD study (contribution of LIH to five of them):
Efavirenz-based simplification after successful early lopinavir-boosted-ritonavir-based therapy in HIV-infected children in Burkina Faso and Côte d’Ivoire: the MONOD ANRS 12206 non-inferiority randomised trial
Virological response and resistances over 12 months among HIV-infected children less than two years receiving first-line lopinavir/ritonavir-based antiretroviral therapy in Cote d’Ivoire and Burkina Faso: the MONOD ANRS 12206 cohort