Antiretroviral drug resistance, HIV-1 tropism, and HIV-1 subtype among men who have sex with men with recent HIV-1 infection

Eshleman, Susan H.; Husnik, Marla; Hudelson, Sarah E.; Donnell, Deborah; Huang, Yijian; Huang, Wei; Hart, Stephen A.; Jackson, J. Brooks; Coates, Thomas J.; Chesney, Margaret A.; Koblin, Beryl A.

doi:10.1097/qad.0b013e32810fd72e

Cited by 52 publications

(42 citation statements)

References 18 publications

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“…Recent studies have found the frequency of X4/DM dualtropic strains in plasma samples from recently infected patients in the United States and Spain to be from 3.2% to 17.5% (14,15,16). Similarly, we found 15.9% (95% confidence interval…”

supporting

confidence: 72%

Low Frequency of CXCR4-Using Viruses in Patients at the Time of Primary Non-Subtype-B HIV-1 Infection

et al. 2010

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We used genotypic and phenotypic assays to estimate the frequency of X4/DM viruses in 131 patients infected with non-subtype-B viruses at the time of primary HIV-1 infection (PHI). All patients were enrolled in the French PRIMO Cohort from 1996 to 2007. Most strains belonged to CRF02_AG (51.1%) and subtype A (14.5%). Sixteen viruses (12.2%) were classified as CXCR4 tropic ("X4 strains") by the combined criteria of amino acids 11 and 25 of the V3 loop (11/25) and net charge rules and/or the SVMgeno2pheno 10% algorithm: 6 strains by the combined genotypic rule, 7 by the SVMgeno2pheno 10% algorithm, and 3, clustering in subtype D, by both algorithms. However, only one strain (0.8%), belonging to subtype A, was defined as a dual-tropic (DM) virus by the phenotypic assay. The 67 CRF02_AG strains included 2 classified as X4 strains by the combined genotypic rule (3%) and 2 others classified as X4 strains by SVMgeno2pheno 10% (3%), but none of these 4 strains was an X4 or DM strain according to the phenotypic assay. These results suggest that the cellular virus reservoir was established with X4 strains in very few non-subtype-B-infected patients at the time of PHI. Genotypic predictions can overestimate the proportion of non-subtype-B X4 viruses at PHI.

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confidence: 72%

Low Frequency of CXCR4-Using Viruses in Patients at the Time of Primary Non-Subtype-B HIV-1 Infection

et al. 2010

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“…In particular, in drug-naive MSM individuals, resistance (3.9%) is lower than that observed in other studies performed on the same risk class [52][53][54] and in other studies performed on heterogeneous risk classes. [55][56][57][58] The prevalence of resistance in antiretroviral-treated MSM individuals is around 60%, with a decreased trend over the years 2004-2006 (data not shown), in line with that observed in recent studies; 59,60 this diminished trend could explain the low prevalence of drug resistance in naive patients.…”

Section: Discussioncontrasting

confidence: 44%

Non-B HIV Type 1 Subtypes among Men Who Have Sex with Men in Rome, Italy

Giuliani

Montieri

Palamara

et al. 2009

AIDS Research and Human Retroviruses

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An increase in the circulation of HIV-1 non-B subtypes has been observed in recent years in Western European countries. Due to the lack of data on the circulation of HIV-1 non-B subtypes among European HIV-1-infected men who have sex with men (MSM), a biomolecular study was conducted in Rome, Italy. HIV-1 partial pol gene sequences from 111 MSM individuals (76 drug naive and 35 drug experienced) were collected during the years [2004][2005][2006]. All these sequences were analyzed using the REGA HIV-1 Subtyping Tool, and aligned using CLUSTAL X followed by manual editing using the Bioedit software. A BLAST search for non-B subtype sequences was also performed. Twenty-six (23.4%) MSM were not Italians. Eight individuals (7.2%) were diag- The CRFs were more prevalent (8.1%) than pure subtypes (5.4%), which were distributed as follows: subtype C (2.6%), subtype A1 (1.7%), and subtype F1 (0.9%). Major mutations conferring resistance to antiretroviral drugs (ARV) were not found among HIV-1 non-B subtype drugnaive patients but were found in two ARV-experienced individuals. The data show that viral diversity is likely increasing in a population group that had been previously characterized by the circulation of HIV-1 subtype B.

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“…Moreover, an additional patient with the R5 variant in plasma had the X4 strain in PBMCs. Recent studies have reported various frequencies of X4 dual/mixed (D/M) dualtropic strains (3.2 to 17.5%) in plasma samples from recently infected patients in the United States and Spain (13,19). A large French epidemiological study demonstrated that a high proportion of patients (62 of 390 patients [15.9%]) harbored X4 or dualtropic viruses in PBMCs at the time of primary infection, suggesting the existence of a cellular X4 viral reservoir that could persist for a lengthy period of time (21).…”

Section: Discussionmentioning

confidence: 99%

HIV Coreceptor Tropism in Paired Plasma, Peripheral Blood Mononuclear Cell, and Cerebrospinal Fluid Isolates from Antiretroviral-Naïve Subjects

et al. 2011

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A survey of HIV coreceptor usage in cerebrospinal fluid (CSF) samples, peripheral blood mononuclear cells (PBMCs), and plasma samples from naïve seropositive patients was conducted. One hundred patients were enrolled in this study. Of the 100 patients, 36 had a primary or recent infection (P-RI), 31 had an early chronic infection (>350 CD4 cells) (ECI), and 33 had a late chronic infection (LCI). All 3 compartments were sampled in a subset of 33 participants, while the remaining 67 patients provided plasma samples and PBMCs only. Seventy-seven patients harbored the R5 virus in plasma samples and had a significantly higher median and percentage of CD4 ؉ T cells than patients with X4 virus (437 and 281 cells/l, respectively; P ‫؍‬ 0.0086; 20.6% and 18.6%, respectively). The X4 strain was detected more frequently in patients with LCI than in patients with P-RI or ECI (39.3%, 19.4%, and 9.6%, respectively; P ‫؍‬ 0.0063). PBMC and plasma tropism was concordant in 90 patients, and 73 had the R5 strain. Among patients with discordant results, 4 had the R5 virus in their plasma and the X4 virus in PBMCs; 6 showed the opposite profile. Plasma, PBMC, and CSF tropism determinations were concordant in 26/33 patients (21 patients had R5, and 5 had X4). The tropism was discordant in 5/33 patients, with the X4 virus in plasma and R5 in CSF; the HIV tropism in PBMCs was X4 in 3 patients. The remaining 2/33 patients had the R5 virus in plasma and PBMCs and the X4 virus in CSF; one of these patients had a P-RI. The discordant tropism in CSF and blood may have implications for chemokine (C-C motif) receptor 5 (CCR5) antagonist use in patients with limited response to antiretroviral therapy (ART) or in responding patients evaluated for simplification of treatment.

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Antiretroviral drug resistance, HIV-1 tropism, and HIV-1 subtype among men who have sex with men with recent HIV-1 infection

Abstract: Antiretroviral drug resistance is relatively common among recently infected men who have sex with men in the United States. CXCR4-using strains were detected in a small number of these infections, which were all subtype B HIV-1.

Cited by 52 publications

References 18 publications

Low Frequency of CXCR4-Using Viruses in Patients at the Time of Primary Non-Subtype-B HIV-1 Infection

Low Frequency of CXCR4-Using Viruses in Patients at the Time of Primary Non-Subtype-B HIV-1 Infection

Non-B HIV Type 1 Subtypes among Men Who Have Sex with Men in Rome, Italy

HIV Coreceptor Tropism in Paired Plasma, Peripheral Blood Mononuclear Cell, and Cerebrospinal Fluid Isolates from Antiretroviral-Naïve Subjects

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