Anti-Gp41 Antibody Levels Reflect HIV Viral Suppression and Cellular Reservoir in Long-Term Antiretroviral-Treated Trial Participants

International audienc

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

International audienceBackground: 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/106 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

Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance

Background Integrase strand transfer inhibitors (INSTIs) are expected to be widely adopted globally, requiring surveillance of resistance emergence and transmission. Objectives We therefore sought to develop a standardized list of INSTI-resistance mutations suitable for the surveillance of transmitted INSTI resistance. Methods To characterize the suitability of the INSTI-resistance mutations for transmitted HIV-1 drug resistance (TDR) surveillance, we classified them according to their presence on published expert lists, conservation in INSTI-naive persons, frequency in INSTI-treated persons and contribution to reduced in vitro susceptibility. Mutation prevalences were determined using integrase sequences from 17302 INSTI-naive and 2450 INSTI-treated persons; 53.3% of the INSTI-naive sequences and 20.0% of INSTI-treated sequences were from non-B subtypes. Approximately 10% of sequences were from persons who received dolutegravir alone or a first-generation INSTI followed by dolutegravir. Results Fifty-nine previously recognized (or established) INSTI-resistance mutations were present on one or more of four published expert lists. They were classified into three main non-overlapping groups: 29 relatively common non-polymorphic mutations, occurring in five or more individuals and significantly selected by INSTI treatment; 8 polymorphic mutations; and 22 rare mutations. Among the 29 relatively common INSTI-selected mutations, 24 emerged as candidates for inclusion on a list of INSTI surveillance drug-resistance mutations: T66A/I/K, E92G/Q, G118R, F121Y, E138A/K/T, G140A/C/S, Y143C/H/R/S, S147G, Q148H/R/K, N155H, S230R and R263K. Conclusions A set of 24 non-polymorphic INSTI-selected mutations is likely to be useful for quantifying INSTI-associated TDR. This list may require updating as more sequences become available from INSTI-experienced persons infected with HIV-1 non-subtype B viruses and/or receiving dolutegravir

Resistance to integrase inhibitors: a national study in HIV-1-infected treatment-naive and -experienced patients

International audienc

Surveillance of HIV-1 primary infections in France from 2014 to 2016: toward stable resistance, but higher diversity, clustering and virulence?

International audienc

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

International audienceObjectives: The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods: Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were .50 copies/mL in both compartments and bulk genotypic tests were realized. Results: On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P ¼ 0.0455) and T215Y (P ¼0.0455). Conclusions: In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performed