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Surveillance studies of Transmitted Drug Resistance (TDR) are crucial in tracking the evolution of HIV epidemiology. Our aim was to investigate TDR to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors (INIs), as well as to new drugs: lenacapavir, fostemsavir. Predictive sensitivity was evaluated for maraviroc and broadly neutralizing antibodies (bNAbs) (zinlirvimab and teropavimab). Between 2020 and 2023, 85 people with HIV (PWH) were diagnosed with primary HIV-1 infection (PHI). Pol and env sequences were analyzed and TDR was characterized according to the French ANRS algorithm. The genotypic-based prediction of bNAbs sensitivity was based on HIV env amino acid signatures I108, I201, F353 for teropavimab and N325, N332, H330 for zinlirvimab. TDR to NRTIs, NNRTIs, PIs and INIs was evidenced in 8.2%, 12.9%, 4.7%, and 5.9% strains, respectively. Ten viruses were CXCR4/dual mix. All viruses were susceptible to lenacapavir (100%) and 52% harbored resistance to fostemsavir. The genotypic profile was associated with a predictive positive value (PPV) > 83% of susceptibility to both teropavimab and zinlirvimab for 23 viruses (31%), while 22 (29%) had a PPV between 62% and 75%, suggesting reduced susceptibility to both bNAbs as soon as primary infection. The surveillance of TDR evidenced at the time of PHI is important with regard to new strategies for HIV patients with virological failure and global implementation of PrEP using NRTI, INI such as recently approved injectable cabotegravir, and future long-acting drugs such as lenacapavir and bNAbs., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

The gut-associated lymphoid tissue represents the largest reservoir of HIV-1. Improving knowledge of this reservoir by studying the diversity of viral population is a key step towards understanding the pathogenesis and dynamics of HIV. Obtaining samples is difficult and little information is available on gut viral quasispecies during the course of infection in humans. The aim of this study was to characterize rectal viral strains and their diversity and to investigate the relationships between the rectal tissue reservoir and viral variants in the blood. Phylogenetic analyses were performed on the env sequences for rectal HIV DNA, blood HIV DNA, and HIV RNA clones, with maximum-likelihood and neighbor-joining methods on seven patients. Genetic diversity was assessed. Higher diversity of HIV DNA clones was noted in the rectum compared to blood in four out of five patients without HAART. Viral diversity was present in the rectum from time of the primary infection. Similar degrees of diversity were observed in the rectum and blood during HAART. Rectal and blood HIV variants were interspersed partially or totally in the seven patients. A certain number of rectal HIV DNA clones were clustered together in six patients. These results suggest that variants in the rectum were more heterogeneous than variants in the blood from patients without HAART, probably because the activated milieu of gut-associated lymphoid tissue may provide an improved environment for viral replication, and indicate exchange of viral populations between blood and rectal tissues, reflecting the dynamics of HIV during course of infection., (Copyright © 2011 Wiley-Liss, Inc.)

Diagnosis of primary HIV-1 infection is challenging due to the presence of a serological window; thus, HIV-1-RNA quantitation and/or measurement of p24 antigenemia are recommended in such cases. A patient was diagnosed at the time of primary HIV-1 infection, he harbored a CFR02_AG subtype virus; quantitation of plasma HIV-1-RNA yielded an undetectable result according to one commercial assay, while HIV-1-RNA was detectable when measured with three other assays., (© 2010 Wiley-Liss, Inc.)

The hepatitis C virus genotype is considered to be the most important baseline predictor of a sustained virological response in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. The influence of the subtype on the sustained virological response was investigated in patients infected with genotypes 1, 4, 5, or 6. This study was done on 597 patients with chronic hepatitis C who were given pegylated interferon and ribavirin for 48 weeks. The overall rate of sustained virological response in the 597 patients was 37.8%. Univariate analysis indicated that the sustained virological response of patients infected with subtype 1b (39%) tended to be higher than that of patients infected with subtype 1a (30.6%; P = 0.06) and it was similar to those patients infected with subtypes 4a (51.3%; P = 0.12) or 4d (51.7%; P = 0.16). Multivariate analysis indicated that five factors were independently associated with sustained virological response: the age (OR 0.97; 95% CI = 0.95-0.99), absence of cirrhosis (OR: 2.92; 95% CI = 1.7-5.0; P < 0.01), absence of HIV co-infection (OR: 2.08; 95% CI = 1.2-3.5; P < 0.01), low baseline plasma HCV RNA concentration (OR: 1.74; 95% CI = 1.2-2.6; P < 0.01), and the subtype 1b (OR: 1.61; 95% CI = 1.0-2.5; P = 0.04) or subtypes 4a and 4d (OR: 2.03; 95% CI = 1.1-3.8; P = 0.03). In conclusion, among difficult-to-treat genotypes, the subtype 1a is associated with a lower response to anti-HCV therapy than subtypes 1b, 4a, and 4d., ((c) 2009 Wiley-Liss, Inc.)

HIV-1 diagnosis in babies born to seropositive mothers is one of the challenges of HIV epidemics in children. A simple, rapid protocol was developed for quantifying HIV-1 DNA in whole blood samples and was used in the ANRS French pediatric cohort in conditions of prevention of mother-to-child transmission. A quantitative HIV-1 DNA protocol (LTR real-time PCR) requiring small blood volumes was developed. First, analytical reproducibility was evaluated on 172 samples. Results obtained on blood cell pellets and Ficoll-Hypaque separated mononuclear cells were compared in 48 adult HIV-1 samples. Second, the protocol was applied to HIV-1 diagnosis in infants in parallel with plasma HIV-RNA quantitation. This prospective study was performed in children born between May 2005 and April 2007 included in the ANRS cohort. The assay showed good reproducibility. The 95% detection cut-off value was 6 copies/PCR, that is, 40 copies/10(6) leukocytes. HIV-DNA levels in whole blood were highly correlated with those obtained after Ficoll-Hypaque separation (r = 0.900, P < 0.0001). A total of 3,002 specimens from 1,135 infants were tested. The specificity of HIV-DNA and HIV-RNA assays was 100%. HIV-1 infection was diagnosed in nine infants before age 60 days. HIV-DNA levels were low, underlining the need for sensitive assays when highly active antiretroviral therapy (HAART) has been given. The performances of this HIV-DNA assay showed that it is adapted to early diagnosis in children. The results were equivalent to those of HIV-RNA assay. HIV-DNA may be used even in masked primary infection in newborns whose mothers have received HAART., ((c) 2008 Wiley-Liss, Inc.)

Tenofovir disoproxil fumarate (TDF) has become an important component of HIV combination therapy because of its potency and once-daily dosing. Key mutation associated with resistance to TDF is a K65R in the reverse transcriptase (RT) gene. According to occurrence of K70E mutation after failure to TDF regimen, this mutation was recently reported as a mutation associated with TDF resistance in most resistance genotypic algorithms. The aim of this study was to analyze, retrospectively, the prevalence and conditions of selection of HIV-1 RT K70E mutation from a national clinical survey. Absence of selection of K70E in 850 HIV-1-infected naive patients suggests its role in NRTI drug resistance. Prevalence of K70E RT was low (99/41601, 0.24%) in patients treated between 1999 and 2005. Conversely with K65R mutation, thymidine analog mutations (TAMs) can be concomitantly observed with K70E mutation but its frequency decreased as the number of TAM increases. Concomitant association of K65R and K70E was possible but infrequent (11%). At the time of K70E selection, 60% of patients had received or received TDF-containing regimen and one-third received exclusive NRTI regimen. In conclusion, the K70E mutation could be an alternative pathway of TDF resistance, but as the K65R mutation, other NRTI as ABC, ddI, and 3TC could be also associated with the K70E selection.

In the USA and West Europe, nearly 80% of HIV-1-infected adults, experiencing virologic failure, harbored virus strain resistant to at least one antiretroviral drug. Limited data are available on antiretroviral drug resistance in pediatric HIV infection. The aims of this study were to analyze prevalence of HIV-1 drug resistance and to identify risk factors associated with resistance in this population. Prevalence of genotypic resistance was estimated retrospectively in treated children who experienced virologic failure (with HIV-1-RNA > 500 copies/ml) followed in Necker hospital between 2001 and 2003. Among 119 children with resistance testing, prevalence of resistance to any drug was 82.4%. Resistance ranged from 76.5% to nucleoside reverse transcriptase inhibitor (NRTI), to 48.7% to non-nucleoside reverse transcriptase inhibitor (NNRTI) and 42.9% to protease inhibitor (PI). Resistance to at least one drug of two classes and three classes (triple resistance) was 31.9 and 26.9%, respectively. Resistance was not associated with geographic origin, HIV-1 subtype, and CDC status. In multivariate analysis, resistance to any drug remained associated independently with current low viral load and high lifetime number of past PI. Triple resistance was independently associated with the high lifetime number of past PI and with gender, particularly among children aged 11 years old or more with a prevalence seven times higher in boys than in girls. In conclusion, antiretroviral resistance is common among treated HIV-1-infected children and prevalence was similar with those observed in adult population in the same year period. However, adolescent boys seem to be at greater risk.

The performance of French virology laboratories belonging to the ANRS network has been assessed annually for 3 years. The performance of these laboratories was compared between the years 2002 and 2003. Ten and 7 coded samples were sent to 38 virology laboratories in 2002 and 45 virology laboratories in 2003, respectively. Each panel of coded samples included at least one HIV-negative control, a pair of duplicate specimens, samples with a wide range of viral loads, and samples with a large number of resistance mutations. The laboratories used their standard sequencing procedures and were asked to report the amino acids at codons associated with resistance mutations, based on the IAS-USA expert panel list. The reference amino acid sequences were defined as those most frequently reported by the participants. The specificity of detection of RT mutations was significantly better in 2003 (99.9%) than in 2002 (99.7%) (P = 0.05). There was no difference between 2002 and 2003 in the specificity of detection of protease mutations (99.6% and 99.8%) or the sensitivity of detection of RT mutations (98.8% and 98.2%). The sensitivity of detection of protease mutations improved significantly between 2002 and 2003 (97.6% and 99.0%, respectively; P = 0.037). The proportion of laboratories reporting fully accurate results, in terms of amplification, specificity, sensitivity, and reproducibility, tended to increase between 2002 and 2003 (P = 0.077). No errors were made by 19% of laboratories in 2002, compared to 42% in 2003. These results show the value of repeated external quality assessments., (Copyright 2005 Wiley-Liss, Inc.)

A retrospective survey estimating the prevalence of hepatitis viruses B (HBV) and C (HCV) was conducted on samples taken in 1,002 African pregnant women (501 diagnosed as HIV-1 positive and 501 HIV-1 negative) participating in a clinical trial program conducted in Abidjan, Côte d'Ivoire (West Africa). Hepatitis B markers studied were HBs antigen (HBsAg), and if positive, HBe antigen/anti-HBe antibodies and HBV DNA. Two third generation (G3) HCV enzyme immunoassays (EIAs) were used for primary HCV screening. All anti-HCV antibody-positive sera were assessed further with supplementary assays (one another G3 EIA, RIBA 3.0, and HCV RNA). HCV genotypes were also determined. HBsAg was found in a similar proportion among HIV-positive (45/499, 9.0%, 95% confidence interval [95% CI], 6.6-11.9) and HIV-negative (40/498, 8.0%, 95% CI, 5.8-10.8) women (P = 0.58). The diagnosis of chronic hepatitis B, based on HBV DNA positive results, was more frequent in HIV-positive women (26.7%), compared to HIV-negative women (9.4%) (P = 0.06). In the case of hepatitis C infection, after supplementary testing allowing the elimination of frequent false-positive screening results, a prevalence rate of about 1% was found, both in HIV-positive (6/501, 1.2%, 95% CI, 0.44-2.59) and HIV-negative (4/501, 0.8%, 95% CI, 0.22-2.03) women (P = 0.53). Of the 10 samples confirmed positive and assessed for HCV RNA, eight (80%) were viraemic and belonged to HCV genotypes 1 or 2. The relative high frequency of HIV/HBV coinfection in Côte d'Ivoire emphasises the need for monitoring the risk of hepatotoxicity by antiretroviral therapy in such patients. We propose an accurate and cost-efficient algorithm for HCV diagnosis in Africa.

The predictive value of two methods for measuring HIV RNA concentration in plasma was assessed in relation to CD4 lymphocyte counts during the asymptomatic period of infection. The design was a retrospective longitudinal case-control study for a mean period of 60 months involving 20 asymptomatic patients included in the French National prospective survey. The CD4 counts in these patients during the last 36 months of the study were stable (non-progressors) or declined (progressors). Plasma RNA concentrations were determined in each subject annually using the AMPLICOR and NASBA techniques. Only AMPLICOR gave RNA titers above the cut-off value for all the patients. The techniques agreed satisfactorily, although there was a difference, median 0.4 log10, between the AMPLICOR and NASBA values. The non-progressors had low and stable RNA concentrations. The concentration was higher in the progressors, according to the AMPLICOR technique, from their inclusion in the study, and according to the NASBA technique, from 1 year after inclusion. However, only four of ten individual progressors had stable plasma HIV RNA concentrations significantly above those of the non-progressors before the decline in their CD4 counts. These were all and only the patients with a decline in lymphocyte counts more than 100 CD4/mm3/year. In each of the other progressors, the RNA concentration was not significantly different from those of the non-progressors. Thus, when making decisions about therapy, plasma HIV RNA determinations cannot be used in place of CD4 counts and may provide valuable additional information.