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Short communication: Transmitted drug resistance and molecular epidemiology in antiretroviral naive HIV type 1-infected patients in Rhode Island.

ABSTRACT: Transmission of HIV-1 drug resistance has important clinical and epidemiological consequences including earlier treatment failure and forward transmission of resistance strains in high-risk groups. To evaluate the prevalence and molecular epidemiology of transmitted drug resistance in Rhode Island, we collected genotypic, demographic, clinical, and laboratory data from treatment-naive individuals presenting to the largest outpatient HIV clinic in the state from January 2007 to November 2007. Sequences from 35 treatment-naive individuals were available, 83% of whom were men who had sex with men (MSM). All sequences were HIV-1 subtype B. Drug resistance mutations were identified in 7/35 [20%; 95% confidence interval (CI), 0.08-0.37] patients, six of whom had K103N. Two phylogenetic transmission clusters were found, involving 17% (6/35) of individuals, three in each cluster. We did not find an association between belonging to a cluster and age, gender, AIDS-defining illness, CD4 cell count, or viral load. Drug resistance mutations were more commonly observed in transmission clusters (p?=?0.08). Individuals in one cluster all had K103N and were MSM who had attended local bathhouses. Individuals forming clusters were significantly more likely to have visited a bathhouse compared to nonclusters (p?=?0.02). The prevalence of transmitted drug resistance in Rhode Island is high, further justifying genotypic testing on presentation to care and prior to treatment initiation. Molecular epidemiological analysis and association of resistance with phylogenetic networks using data obtained for clinical purposes may serve as useful tools for the prevention of drug resistance transmission and for contact tracing.

SUBMITTER: Chan PA

PROVIDER: S-EPMC3048815 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Short communication: Transmitted drug resistance and molecular epidemiology in antiretroviral naive HIV type 1-infected patients in Rhode Island.

Chan Philip A PA Tashima Karen K Cartwright Charles P CP Gillani Fizza S FS Mintz Orli O Zeller Kimberly K Kantor Rami R

AIDS research and human retroviruses 20101018 3

Transmission of HIV-1 drug resistance has important clinical and epidemiological consequences including earlier treatment failure and forward transmission of resistance strains in high-risk groups. To evaluate the prevalence and molecular epidemiology of transmitted drug resistance in Rhode Island, we collected genotypic, demographic, clinical, and laboratory data from treatment-naive individuals presenting to the largest outpatient HIV clinic in the state from January 2007 to November 2007. Seq ...[more]

PMID: 20954831

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Project description:Human immunodeficiency virus type 1 (HIV-1) prevalence and incidence in the fishing communities on Lake Victoria in Uganda are high. This population may play a role in driving the HIV epidemic in Uganda including the spread of transmitted drug resistance (TDR). We report data on TDR in this population among antiretroviral (ARV)-naive, recently infected individuals about 5 years after ARV scaling-up in Uganda. We identified phylogenetic transmission clusters and combined these with volunteer life histories in order to understand the sexual networks within this population. From a prospective cohort of 1,000 HIV-negative individuals recruited from five communities, 51 seroconverters were identified over a period of 2 years. From these, whole blood was collected and population sequencing of the HIV-1 pol gene (protease/reverse transcriptase) was performed from plasma. Drug resistance mutations (DRMs) were scored using the 2009 WHO list for surveillance of TDR. TDR prevalence categories were estimated using the WHO recommended truncated sampling technique for the surveillance of TDR for use in resource-limited settings (RLS). Of the samples 92% (47/51) were successfully genotyped. HIV-1 subtype frequencies were 15/47 (32%) A1, 20/47 (43%) D, 1/47 (2%) C, 1/47 (2%) G, and 10/47 (21%) unique recombinant forms. Nonnucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutation K103N was identified in two individuals and V106A in one (6%) suggesting that the level of TDR was moderate in this population. No nucleoside/tide reverse transcriptase inhibitor (NRTI) or protease inhibitor (PI) DRMs were detected. In this study, we identified five transmission clusters supported by high bootstrap values and low genetic distances. Of these, one pair included the two individuals with K103N. Two of the genotypic clusters corresponded with reported sexual partnerships as detected through prior in-depth interviews. The level of TDR to NNRTIs in these ARV-naive individuals was moderate by WHO threshold survey categorization. The transmission clusters suggest a high degree of sexual partner mixing between members of these communities.

Project description:HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15-59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5%) of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7-17.1). No TDR was observed among persons with AHI (n = 7). TDR prevalence was 4.6% (95% CI 1.8-11.2) for nucleoside reverse transcriptase inhibitors (NRTIs), 6.9% (95% CI 3.2-14.2) for non- nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.2% (95% CI 0.2-6.2) for protease inhibitors. Three (3.4% 95% CI 0.8-10.1) persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%), C (6.9%), D (21.8%), G (2.3%), and circulating recombinant forms (11.5%). Only low CD4 count was associated with TDR (p = 0.0145). Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population-based therapeutic guidelines and public health interventions.

Dataset Information

Short communication: Transmitted drug resistance and molecular epidemiology in antiretroviral naive HIV type 1-infected patients in Rhode Island.

Publications

Short communication: Transmitted drug resistance and molecular epidemiology in antiretroviral naive HIV type 1-infected patients in Rhode Island.

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