Characterization of drug resistance and the defective HIV reservoir in virally suppressed vertically infected children in Mali.

BACKGROUND: In the perspective of ART-free HIV remission, vertically infected children treated with suppressive ART from early infancy represent an optimal population model to better understand the genetic complexity of the reservoir. OBJECTIVES: To evaluate the proportion of defective viral population and the genotypic resistance patterns in cell-associated HIV DNA. METHODS: In a cohort including 93 ART-treated vertically HIV-infected (VHIV) children in Mali with plasma HIV-1 RNA ≤50 copies/mL for at least 6 months, we studied total HIV DNA, percentage of defective genomes and resistance by reverse transcriptase and protease bulk sequencing from whole blood in dried blood spots. RESULTS: Children had a median age of 9.9 years at the time of inclusion (IQR = 7.6-13.4) and 3.3 years (IQR = 2-7) at ART initiation; median ART duration was 5.5 years (IQR = 3.7-7.3). The median level of total HIV DNA was 470 copies/106 cells with one patient presenting undetectable HIV DNA (<66 copies/106 cells). We observed the presence of at least one stop codon in viruses from 34 patients (37%). The presence of stop codons was not correlated with the level of HIV DNA or duration of ART. We showed a high prevalence of HIV-1 resistance in DNA with 26% of children harbouring virus resistant to at least one NRTI and 40% to at least one NNRTI. CONCLUSIONS: While these VHIV children were successfully treated for a long time, they showed high prevalence of resistance in HIV DNA and a moderate defective HIV reservoir.

Qualitative and quantitative HIV antibodies and viral reservoir size characterization in vertically infected children with virological suppression.

Background: Absence of detectable viraemia after treatment cessation in some vertically HIV-infected (VHIV) children suggests that early initiation of HAART could lead to functional cure. Objectives: We described the factors associated with HIV antibody levels and the viral reservoir size in HAART-treated VHIV children. Methods: Study included 97 VHIV children with virological suppression, in Bamako, Mali. The anti-gp41 antibody activities and HIV serostatus were assessed. The viral reservoir size was measured by quantifying total cell-associated HIV DNA. Results: Among the children studied, the median total HIV DNA level was 445 copies/10 6 cells (IQR = 187-914) and the median anti-gp41 antibody activity was 0.29 OD (IQR = 0.18-0.75). Low activity of anti-gp41 antibodies was associated with a younger age of HAART initiation ( P = 0.01). Overall, eight HIV-1 seroreversions were identified. Conclusions: Study identified potential candidates with low viral reservoir and low antibody levels or activities for future trials aiming to reduce HIV-1 reservoir to limit HAART duration.