Search

Significant subtype-specific differences were observed in the protease (PR) region of the HIV-1 pol gene. Most of the previous studies were restricted to subtype B, although subtype C accounts for more than 50% of HIV infections worldwide. In this study we characterized PR sequences from primary clinical isolates from protease inhibitor (PI)-naive patients in South India (n=39) as well as database-derived HIV-1 subtype C sequences from India (n=542) and globally (n=2970). All the study sequences were identified as subtype C, which is predominant in India. Drug resistance genotyping analysis identified 2.6% (1/39) prevalence of major PI resistance (I54T) and 7.7% (3/39) of minor PI resistance (L10I, T74S, and A71T). Selection of T12S, I15V, L19I, M36I, R41K, H69K, L89M, and I93L was observed both in global and Indian subtype C while the L63P mutation was selected in Indian PR sequences. Three different codon-based maximum likelihood methods agreed on four sites (12, 19, 36, and 82) under positive selection in Indian sequences.

The majority of the HIV drug resistance (HIVDR) testing studies have focused on subtype B virus. The predominance of subtype C in the Indian subcontinent along with greater access to antiretroviral therapy (ART) necessitates studies on HIVDR genotyping. We determined the prevalence of mutations associated with protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and nonnucleoside reverse transcriptase inhibitors (NNRTI) from plasma of 40 antiretroviral drug-naive study participants in Indian HIV-1 pol gene sequences. Of these, 36 sequences belonged to subtype C, two to subtype A1, and two were subtype A1C recombinants. The heterosexual route was the most common route of transmission. Drug resistance-associated mutations were observed in 10% (4/40) of the study participants. The resistance mutation observed in the protease gene was V82A, whereas in the RT gene, M41L, D67N, M184V, and A98G were documented. This is the first study reporting major protease mutations by genotyping in ART-naive individuals from western India.

Context: Over the past few years, reports of emergence and transmission of drug-resistant strains of HIV have increased, especially in western countries. In the context of increased widespread use of zidovudine- and lamivudine-based combinations in India, coupled with the genetic diversity of HIV, it is essential to generate preliminary data on the frequency of zidovudine- and lamivudine-resistant variants of HIV-1 in North India., Objectives: In the present study, the authors screened for mutations in the pol gene of HIV-1 associated with resistance to zidovudine and lamivudine in HIV-infected treatment-naive patients from North India., Design and Patients: The mutations were screened at codons 70 and 215 (conferring resistance to zidovudine) and at codon 184 (conferring resistance to lamivudine) by using a nested amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) approach from the proviral DNA of 60 patients., Results: Most of the patients showed a mixture of both wild-type and mutant virus. In all but 1 patient, wild-type virus was observed with respect to each codon. Mutant variants were also observed in many patients, especially at codon 70 (48 patients [80%]) and codon 184 (19 patients [31.67%]). In contrast, the frequency of mutation at codon 215 was found to be very low (1 patient [1.67%])., Conclusions: In this sample of treatment-naive HIV-1-infected patients in North India, a high proportion of mutant variants harbored mutations in the pol gene at codons- 70 and 184 coexisting with wild-type HIV-1.

Screening of drug-resistant variants is very important for the effective clinical management of HIV-infected patients and development of new strategies. The present study was aimed to detect codon-184 mutations in the pol-gene of HIV leading to resistance to lamivudine (3-TC) by nested cum ARMS-PCR approach in 10 treated and 9 treatment naive patients. For correlation the whole blood CD4/CD8 cell counts and the soluble TNFRII levels in plasma were also determined. Of the 19 patients tested, mutant variants were observed in 2 patients (Met Val in one and Met Val & lle in second) both being treated with 3-TC. No mutations were detected in the treatment-naive patients. The results confirmed that, drug resistant variants of codon-184 emerge rapidly in patients receiving 3-TC containing regimens including our population, which is mainly infected with subtypeC of the virus that could be detected along with wild viral population using sensitive approaches such as ARMS-PCR.

HIV-1 isolates are classified phylogenetically in several subtypes or clades according to env and gag coding sequences. Viral subtypes tend to cluster geographically. DNA sequences encoding the p51 subunit of reverse transcriptase were obtained by nested polymerase chain reaction from peripheral blood mononuclear cells of two HIV-1-seropositive individuals from New Delhi and three from Pune, in northern and western India, respectively. These isolates were previously characterized as subtype C according to their env sequences. Based on phylogenetic analysis, the reverse transcriptase coding region of these isolates is distinct from those of subtype A, subtype B, subtype D, and group O of HIV-1 viruses. The nucleotide divergence of these Indian pol sequences (3.3%) is similar to that of existing sequences for subtype B and subtype D viruses. This result supports the epidemiologic data of a more recently introduced HIV-1 epidemic in India. Based on the corresponding env sequences, the pol sequences described in this report are subtype C.

High prevalence of human T-cell lymphotropic virus type I (HTLV-I) infection and disease has been identified among Iranian-born Mashhadi Jews, an ethnically segregated, highly inbred population. To determine the origin and genetic diversity of HTLV-I in this group, 1,039 bp spanning selected regions of the HTLV-I gag, pol, env and pX genes were enzymatically amplified and sequenced directly from DNA of five Mashhadi Jews (three with spastic myelopathy and two asymptomatic carriers). Alignment and comparison of these sequences with cosmopolitan and Australo-Melanesian topotypes of HTLV-I indicated that the HTLV-I strains from Mashhadi Jews, which were > or = 99.9% identical among themselves, exhibited considerable sequence similarity (> or = 99%) to HTLV-I strains from southern India, suggesting a common source of infection. Phylogenetic analysis, using the maximum parsimony method, was consistent with a single-source introduction of HTLV-I into the Mashhadi Jewish community.