Molecular diversity of HIV‐1 and surveillance of transmitted drug resistance variants among treatment Naïve patients, 5 years after active introduction of HAART in Kuala Lumpur, Malaysia

Abstract

Expansion of antiretroviral treatment programs have led to the growing concern for the development of antiretroviral drug resistance. The aims were to assess the prevalence of drug resistant HIV-1 variants and to identify circulating subtypes among HAART-naïve patients. Plasma specimens from N = 100 HIV+ HAART-naïve adult were collected between March 2008 and August 2010 and viral RNA were extracted for nested PCR and sequenced. PR-RT sequences were protein aligned and checked for transmitted drug resistance mutations. Phylogenetic reconstruction and recombination analysis were performed to determine the genotypes. Based on the WHO consensus guidelines, none of the recruited patients had any transmitted drug resistance mutations. When analyzed against the Stanford guidelines, 35% of patients had at least one reported mutation that may reduce drug susceptibility to PI (24%), NRTI (5%), and NNRTI (14%). The commonly detected mutation that may affect current first line therapy was V179D (3%), which may lead to reduced susceptibility to NNRTI. The predominant circulating HIV-1 genotypes were CRF01_AE (51%) and CRF33_01B (17%). The prevalence of unique recombinant forms (URF) was 7%; five distinct recombinant structures involving CRF01_AE and subtype B' were observed, among them a cluster of three isolates that could form a novel circulating recombinant form (CRF) candidate. Transmitted drug resistance prevalence among HAART-naïve patients was low in this cohort of patients in Kuala Lumpur despite introduction of HAART 5 years ago. Owing to the high genetic diversity, continued molecular surveillance can identify the persistent emergence of HIV-1 URF and novel CRF with significant epidemiological impact.

Extensive Genetic Diversity of HIV-1 in Incident and Prevalent Infections among Malaysian Blood Donors: Multiple Introductions of HIV-1 Genotypes from Highly Prevalent Countries

“…On the other hand, 11 partial gag -PR (HXB2: 1753–2591, 834bp) and 2 RT gene (HXB2: 2476–3440, 966bp) sequences were also amplified. Transmitted antiretroviral drug resistance mutation was not detected in the population, similar to previous drug resistance surveillance studies reported among antiretroviral-naïve patients in the country [13,25]. Based on the neighbour-joining phylogenetic tree analysis, HIV-1 genotypes mainly co-circulating in the region including CRF01_AE was detected among 40.9% (n = 61) of the blood donors, followed by CRF33_01B (n = 32, 21.5%) and subtype B (n = 15, 10.1%, including the subtype B variant of Thai origin, B') ( Fig 1 ).…”

“…Based on phylogenetic reconstruction of the partial gag-pol genes, we identified three main HIV-1 genotypes commonly circulating in various risk populations, including CRF01_AE, subtype B (including subtype B') and CRF33_01B [13–15] which attributed to around 73% of the total HIV-1 infections among the blood donors. We observed a higher prevalence of the Western subtype B (around 10%) compared to subtype B', which was reportedly circulating predominantly among the MSM populations in the country and elsewhere in the region [13,26].…”

“…We observed a higher prevalence of the Western subtype B (around 10%) compared to subtype B', which was reportedly circulating predominantly among the MSM populations in the country and elsewhere in the region [13,26]. Of note, we also observed an increased frequency of CRF54_01B (around 4%) which was previously described at a lower frequency among various risk populations [13,18], indicating the establishment of CRF54_01B in the general population and its possible expansion as one of the major recombinant genotypes in the country.…”

“…For example, subtype B (including the Thai variant of subtype B') and CRF01_AE were commonly circulating among men who have sex with men (MSM) and heterosexuals, respectively [13]. Although CRF33_01B co-circulated among various risk populations in the country [14], it has been recently reported to be highly prevalent among the PWIDs [15].…”

“…Recently, at least five newly emerging clades of HIV-1 genetic variants circulating at a lower prevalence have been characterised in the country, namely CRF52_01B, CRF53_01B, CRF54_01B, CRF58_01B and CRF74_01B [16–20]. In addition, the continuous genetic recombination involving CRF01_AE and subtype B has also resulted in the emergence of various unique recombinant forms (URFs) displaying distinct mosaic recombination structures in the region [13,15,21]. …”