Drug resistance in HIV-infected children is one of the main contributors to antiretroviral treatment (ART) failure, especially in developing countries. Sub-Saharan Africa has the largest burden of pediatric HIV infection in the world. Herein, we systematically review the current status of ART failure in HIV-infected African children. A literature search for publications within 10 years was performed through PubMed to identify relevant articles. Included studies examined the impact of timing of ART initiation, criteria for diagnosing therapeutic failure, predictors of therapeutic failure, management strategies and future directions to minimize failure rates in these pediatric populations. Although there is scale-up of ART programs in Africa, novel therapeutic and management strategies are needed to overcome current challenges.
Resistance genotypes in pol gene of HIV-1 were obtained by the ViroSeq® HIV-1 Genotyping System v2.0 (Celera Diagnostics, Alameda, CA, USA) in 138 of 145 (95%) antiretroviral treatment-experienced adults in virological failure living in Central Africa (Cameroon, Central African Republic, Chad, Gabon). HIV-1 group M exhibited broad genetic diversity. Performance of the 7 ViroSeq® sequencing primers showed high failure rate, from 3% to 76% (D: 76%; F: 17%; A and H: 15%; G and B: 4%; C: 3%). These findings emphasize the need of updating the ViroSeq® HIV-1 genotyping system for non-B subtypes HIV-1.
Maternal viral load and immune status, timing and route of delivery, viral subtype, and host genetics are known to influence the transmission, acquisition and disease progression of human immunodeficiency virus-1 (HIV-1) infection. This review summarizes the findings from published works on host molecular factors and virus genotypes affecting mother to child transmission (MTCT) in Africa and identifies the gaps that need to be addressed in future research. Articles in PubMed, Google and AIDSearch and relevant conference abstracts publications were searched. Accessible articles on host factors and viral genetics impacting the MTCT of HIV, done on African populations till 2015 were downloaded. Forty-six articles were found and accessed; 70% described host genes impacting the transmission. The most studied gene was the CCR5 promoter, followed by the CCR2-64I found to reduce MTCT; then SDF1-3’A shown to have no effect on MTCT and others like the DC-SIGNR, CD4, CCL3 and IP-10. The HLA class I was most studied and was generally linked to the protective effect on MTCT. Breast milk constituents were associated to protection against MTCT. However, existing studies in Sub Saharan Africa were done just in few countries and some done without control groups. Contradictory results obtained may be due to different genetic background, type of controls, different socio-cultural and economic environment and population size. More studies are thus needed to better understand the mechanism of transmission or prevention.
Background and objectivesThe association of chemokine receptor-2 (CCR2) polymorphism with HIV transmission or disease progression remains highly controversial. The role of CCR2-64I allele in HIV infection may differ from one population to another because of their genetic background. The objectives of this study were to characterize the CCR2 genetic polymorphism and to determine its potential effect in HIV acquisition in children living in the Northern Region of Cameroon.Materials and methodsA cross-sectional study was carried out in five health facilities in the Northern region of Cameroon. DNA was extracted from the Buffy coat of each participant using the QIAamp®DNA mini kit. The DNA extract was then subjected to polymorphic analyses. CCR2 genotypes were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The Chi-Squared test was used for the assessment of the Hardy-Weinberg equilibrium.ResultsA total of 134 children under 15 years comprised of 38 HIV-exposed infected (28.36%) and 96 HIV-exposed un-infected (71.64%) participants were recruited. Prevalences of 44.78% wild type homozygous, 48.52% heterozygous and 6.7% mutant homozygous alleles were found in the overall population. An allelic frequency of 29.69% for the mutant allele CCR2-64I was found in HIV-exposed un-infected individuals as compared to 34.21% in HIV-infected children (p=0.47).ConclusionThe CCR2-64I allele is relatively common in the Northern Region of Cameroon, with a similar distribution among HIV-exposed un-infected and infected children. As this allele alone does not seem to confer protection against HIV-1 infection, further studies using genotype-combination of CCR2 polymorphism and other single nucleotide polymorphisms would be of great relevance in both HIV prevention and novel therapeutic strategies.
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