Epidemiology, Diagnosis algorithms and prognostic role of Immunologic and Inflammatory Markers among HIV-2 infected individuals in West Africa
TMA2016CDF1597
EDCTP2
Career Development Fellowship (CDF)
This study will be organized into three axes, each with specific objectives. Axis 1: Epidemiology The aim is to provide accurate estimates of HIV-2 prevalence in West Africa using a mixed-method approach. The specific objectives are: • To estimate the prevalence of HIV-2 infection in west African countries using national health and demographic survey data • To estimate the proportion of new HIV-2 infected patients in west African countries based on laboratory surveillance platform • To realize mathematic modification on HIV-2 prevalence worldwide using existing datasets Axis 2: Diagnosis The aim is to improve the diagnosis and classification of HIV-2 and dually infected patients using molecular biology. The specific objectives are: • To confirm the HIV-1 & HIV-2 dual infection using molecular biology To describe the prevalence of dual infections in the WADA HIV-2 cohorts To evaluate a diagnostic algorithm based on rapid HIV tests for the routine diagnosis of dual infection in West Africa Axis 3: Disease progression and inflammatory markers: To describe the proportion and characteristics of long-term non-progressors and elite controllers among HIV-2 infected individuals in the WADA HIV-2 cohort To describe morbidity, disease progression and correlates among HIV-2 infected individuals in West Africa • To describe the temporal evolution of soluble biomarkers of inflammation and the correlation with morbidity and disease progression
Axis 1: Epidemiology of HIV-2 infection First we will estimate the prevalence of HIV-2 infection: the estimates of the national prevalence of HIV-2 infection will be based on the testing of the dried blood spot collected during the last national demography and health survey (DHS) organized in selected participating countries where DHS was recently conducted. The HIV diagnosis during the DHS is based on the use of two serial ELISA tests. No discriminative test is used during the DHS laboratory analyses. According to the methodology of DHS in most West African countries, after the survey, the DBS are stored in the referral laboratory till the next DHS round. This survey will be conducted in collaboration with the national HIV program of each participating center. The DBS of HIV positive DHS participants will be collected in each country and transferred to the CEDRES in Côte d’Ivoire, were an indirect immuno-enzymatic test allowing the qualitative detection of both HIV-1 (gp120) and HIV-2 (gp36) antibodies will be performed. This test has been adapted from Francis Barin’s essay for HIV-1 (40), and has shown 98% specificity (41) and 80% concordance with real-time DNA PCR (18). It is approved by the French National AIDS Research Agency (ANRS) and routinely used in the reference laboratory of the study as homemade Elisa.
Human immunodeficiency virus type 2 (HIV-2) is a retrovirus responsible for an AIDS epidemic localized in West Africa, were the circulation of both HIV-1 and HIV-2 leads to co-infections with both viruses (HIV-1&2). The HIV-2 infection is characterized by a longer asymptomatic phase and a slower disease progression than HIV-1 infection, as well as the intrinsic resistance of HIV-2 to non-nucleoside reverse transcriptase inhibitors (NNRTIs). It is mandatory to differentiate HIV-1 from HIV-2 infection before initiating antiretroviral therapy (ART), but the diagnosis is still challenging, especially for the HIV-1 and HIV-2 dually infected individuals. It is then critical to explore new diagnosis algorithm based on routinely used HIV rapid tests, to ensure the peripheral diagnosis of patients dually infected in West Africa. Another challenge is the difficulty to describe the epidemiology of HIV-2 and dual infection in West Africa. The conflicting report on the epidemic trend of HIV-2 infection and the lack of updated data lead to low consideration for HIV-2 infected patients in the WHO guidelines for antiretroviral therapy. In the context of challenging access to integrase inhibitors in Africa, generating updated data on the epidemiology of HIV-2 infection is critical to enhance the advocacy and improve the holistic care of people living with HIV-2. Furthermore, the important mortality reported among HIV-2 infected individuals may be the consequence of immune activation and persistence of soluble biomarkers as demonstrated in HIV-1 infection. However, the role and mechanism of immunologic and inflammatory biomarkers on disease progression and prognosis of HIV-2 infected patients are still poorly understood. Thus, providing a better understanding of morbidity, disease progression and the role of soluble biomarkers in the prognosis of HIV-2 infected individuals could improve the holistic care of these patients. This research project will rely on the West African HIV-2 cohort, and the related biobank to (i) evaluate new diagnosis algorithm for HIV-1&2 dual infection, (ii) produce more accurate and updated epidemiologic data on HIV-2 infection and (iii) explore disease progression and prognostic role of immunologic and inflammatory markers in HIV-2 infection. A mix-method approach including longitudinal analysis, demographic survey sampling and geospatial modelling, as well as specific biological testing on biobank samples, will be developed during three-years research project. The accurate epidemiologic data, the improved diagnosis of HIV-2 patients and the better understanding of dynamics and correlates of disease progression that will arise from this project, will help inform specific guidelines for HIV-2 infection. This project is organized in three different axes, allowing the exploration of the main questions regarding HIV-2 infection. This configuration allow the recruitment of graduate students in epidemiology, immunology and biostatistics, who will be trained and have the opportunity to develop skill in research under the supervision of the fellow. Finally, the results and the scientific production expected from this grant will be essential for the career development of the fellow who will then established as senior researcher in his field.
Department | Institution | Country |
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clinical and operational research | Programme PACCI | Cote D'ivoire |
Elizabeth Glazer Pediatric AIDS Foundation / PACCI Research Center
Associate Director of Public Health Evaluation / Project Coordinator
The long-term prognosis of HIV-2-infected patients receiving antiretroviral therapy (ART) is still challenging, due to the intrinsic resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) and the suboptimal response to some protease inhibitors (PI). The objective was to describe the 5-years outcomes among HIV-2 patients harboring drug-resistant viruses.
A clinic-based cohort of HIV-2-patients experiencing virologic failure, with at least one drug resistance mutation was followed from January 2012 to August 2017 in Côte d’Ivoire. Follow-up data included death, lost to follow-up (LTFU), immuno-virological responses. The Kaplan-Meier curve was used to estimate survival rates.
A total of 31 HIV-2 patients with virologic failure and with at least one drug resistance mutation were included. Two-third of them were men, 28(90.3%) were on PI-based ART-regimen at enrolment and the median age was 50 years (IQR = 46–54). The median baseline CD4 count and viral load were 456 cells/mm3 and 3.7 log10 c/mL respectively, and the participants have been followed-up in median 57 months (IQR = 24–60). During this period, 21 (67.7%) patients switched at least one antiretroviral drug, including two (6.5%) and three (9.7%) who switched to a PI-based and an integrase inhibitor-based regimen respectively. A total of 10(32.3%) patients died and 4(12.9%) were LTFU. The 36 and 60-months survival rates were 68.5% and 64.9%, respectively. Among the 17 patients remaining in care, six(35.3%) had an undetectable viral load (<50 c/mL) and for the 11 others, the viral load ranged from 2.8 to 5.6 log10 c/mL. Twelve patients were receiving lopinavir at the time of first genotype, five(42%) had a genotypic susceptibility score (GSS) ≤1 and 4(33%) a GSS >2.
The 36-months survival rate among ART-experienced HIV-2 patients with drug-resistant viruses is below 70%,lower than in HIV-1. There is urgent need to improve access to second-line ART for patients living with HIV-2 in West Africa