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1.  Prevalence of Sexually Acquired Antiretroviral Drug Resistance in a Community Sample of HIV-Positive Men Who Have Sex with Men in New York City 
AIDS Patient Care and STDs  2011;25(5):287-293.
To examine antiretroviral (ARV) drug resistance, we recruited a community sample (n=347) of sexually active HIV-positive men who have sex with men (MSM) in New York City, each of whom completed a structured interview and donated a blood sample for HIV genotyping. Participants reported high levels of sexual activity, with 94.6% reporting at least one sexual contact in the past month, and an average of 3.13 partners during this time. Anal intercourse was common, with 70.7% reporting at least one act of insertive anal intercourse (21% of whom reported ejaculating inside their partner without a condom) and 62.1% reporting at least one act of receptive anal intercourse during this time (22.6% of whom received ejaculate without a condom). Seventeen percent reported having sex with a woman in the past year. Although 17.4% of participants reported having ever injected drugs, no association was found between injection and antiretroviral resistance. Average HIV diagnosis was 12.1 years prior to the interview, and 92.1% had taken ARV medication. Sexually transmitted infections (STIs) were widely reported, with 78% having been diagnosed with an STI since being diagnosed with HIV. A genotype was obtained for 188 (54.7%) of the samples and 44.7% revealed mutations conferring resistance to at least one ARV. Resistance to at least one ARV within a given class of medication was most common for nucleoside reverse transcriptase inhibitors (30.3%) and non-nucleoside reverse transcriptase inhibitors (27.7%) and least common for protease inhibitors (18.1%). The combination of high prevalence of antiretroviral resistance and risky sexual practices makes transmission between sex partners a likely mode of acquisition.
PMCID: PMC3085952  PMID: 21457055
2.  Evaluation of Pooling Strategies for Acute HIV-1 Infection Screening Using Nucleic Acid Amplification Testing▿ 
Journal of Clinical Microbiology  2011;49(10):3667-3668.
A 128-member specimen pooling scheme for acute HIV infection (AHI) detection was evaluated using 21 AHI specimens (range, 1,520 to 500,000 copies/ml) previously identified by RNA testing of 16-member plasma pools. HIV-1 RNA was detectable in 128-member pools for all 21 specimens; however, one pool created from a specimen with 1,827 copies/ml was nonreactive in one of three replicates.
PMCID: PMC3187297  PMID: 21832020
3.  Evolution and Recombination of Genes Encoding HIV-1 Drug Resistance and Tropism during Antiretroviral Therapy 
Virology  2010;404(1):5-20.
Characterization of residual plasma virus during antiretroviral therapy (ART) is a high priority to improve understanding of HIV-1 pathogenesis and therapy. To understand the evolution of HIV-1 pol and env genes in viremic patients under selective pressure of ART, we performed longitudinal analyses of plasma-derived pol and env sequences from single HIV-1 genomes. We tested the hypotheses that drug resistance in pol was unrelated to changes in coreceptor usage (tropism), and that recombination played a role in evolution of viral strains. Recombinants were identified by using Bayesian and other computational methods. High-level genotypic resistance was seen in ~70% of X4 and R5 strains during ART. There was no significant association between resistance and tropism. Each patient displayed at least one recombinant encompassing env and representing a change in predicted tropism. These data suggest that, in addition to mutation, recombination can play a significant role in shaping HIV-1 evolution.
PMCID: PMC3186207  PMID: 20451945
HIV-1 drug resistance; HIV-1 recombination; HIV-1 tropism
4.  Accessory Protein 5a Is a Major Antagonist of the Antiviral Action of Interferon against Murine Coronavirus▿  
Journal of Virology  2010;84(16):8262-8274.
The type I interferon (IFN) response plays an essential role in the control of in vivo infection by the coronavirus mouse hepatitis virus (MHV). However, in vitro, most strains of MHV are largely resistant to the action of this cytokine, suggesting that MHV encodes one or more functions that antagonize or evade the IFN system. A particular strain of MHV, MHV-S, exhibited orders-of-magnitude higher sensitivity to IFN than prototype strain MHV-A59. Through construction of interstrain chimeric recombinants, the basis for the enhanced IFN sensitivity of MHV-S was found to map entirely to the region downstream of the spike gene, at the 3′ end of the genome. Sequence analysis revealed that the major difference between the two strains in this region is the absence of gene 5a from MHV-S. Creation of a gene 5a knockout mutant of MHV-A59 demonstrated that a major component of IFN resistance maps to gene 5a. Conversely, insertion of gene 5a, or its homologs from related group 2 coronaviruses, at an upstream genomic position in an MHV-A59/S chimera restored IFN resistance. This is the first demonstration of a coronavirus gene product that can protect that same virus from the antiviral state induced by IFN. Neither protein kinase R, which phosphorylates eukaryotic initiation factor 2, nor oligoadenylate synthetase, which activates RNase L, was differentially activated in IFN-treated cells infected with MHV-A59 or MHV-S. Thus, the major IFN-induced antiviral activities that are specifically inhibited by MHV, and possibly by other coronaviruses, remain to be identified.
PMCID: PMC2916514  PMID: 20519394
5.  Prevalence of Drug-Resistance Mutations and Non–Subtype B Strains Among HIV-Infected Infants From New York State 
Prevalence studies indicate that transmission of drug-resistant HIV has been rising in the adult population, but data from the perinatally infected pediatric population are limited. In this retrospective study, we sequenced the pol region of HIV from perinatally infected infants diagnosed in New York State in 2001–2002. Analyses of drug resistance, subtype diversity, and perinatal antiretroviral exposure were conducted, and the results were compared with those from a previous study of HIV-infected infants identified in 1998–1999. Eight of 42 infants (19.1%) had provirus carrying at least 1 drug-resistance mutation, an increase of 58% over the 1998–1999 results. Mutations conferring resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors were detected in 7.1%, 11.9%, and 2.4% of specimens, respectively. Consistent with previous results, perinatal antiretroviral exposure was not associated with drug resistance (P = 0.70). Phylogenetic analysis indicated that 16.7% of infants were infected with a non–subtype B strain of HIV. It seems that drug-resistant and non–subtype B strains of HIV are becoming increasingly common in the perinatally infected population. Our results highlight the value of resistance testing for all HIV-infected infants upon diagnosis and the need to consider subtype diversity in diagnostic and treatment strategies.
PMCID: PMC2925654  PMID: 16868498
perinatal; HIV drug resistance; subtype diversity; prevalence
6.  Performance of the Aptima HIV-1 RNA Qualitative Assay with 16- and 32-Member Specimen Pools ▿ †  
Journal of Clinical Microbiology  2010;48(9):3343-3345.
The Aptima HIV-1 RNA qualitative assay tested with a WHO-approved HIV type 1 RNA standard in 16- and 32-member pools detected 100% of the pools (1,070 and 2,130 HIV-1 RNA copies/ml/pool, respectively), thus exceeding the FDA-required lower limit of detection. The Aptima test can be used to screen for acute-phase HIV infection.
PMCID: PMC2937729  PMID: 20592141

Results 1-6 (6)