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ABSTRACT
Year : 2013  |  Volume : 34  |  Issue : 1  |  Page : 53-55
 

Abstracts from current global literature: ART resistance in reference to Indian population


Department of Skin and VD, Mahatma Gandhi Institute of Medical Sciences, Sewagram, Wardha, Maharashtra, India

Date of Web Publication4-Jun-2013

Correspondence Address:
Sonia Jain
Department of Skin and VD, Mahatma Gandhi Institute of Medical Sciences, Sewagram, Wardha, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


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How to cite this article:
Jain S. Abstracts from current global literature: ART resistance in reference to Indian population. Indian J Sex Transm Dis 2013;34:53-5

How to cite this URL:
Jain S. Abstracts from current global literature: ART resistance in reference to Indian population. Indian J Sex Transm Dis [serial online] 2013 [cited 2019 Dec 7];34:53-5. Available from: http://www.ijstd.org/text.asp?2013/34/1/53/112942


The association between HIV-1 subtype c antiretroviral resistance and HLA prevalence in South India

Saravanan S, Madhavan V, Murugavel KG, Balakrishnan P, Solomon SS, Umapathy S, Kantor R, Kumarasamy N, Yepthomi T, Smith DM, Mayer KH, Solomon S. J Acquir Immune Defic Syndr 2011;57:e17-19.

Antiretroviral drug resistance and escape from cytolytic T lymphocytes (CTL) are the major obstacles in the control of HIV replication. Therefore, it is important to understand the complex interactions of viral escape and the host immune response, particularly in association with specific drug-resistant mutations (DRMs) to one or more of the three extensively used antiretroviral treatment (ART) classes (nucleoside reverse transcriptase (RT) inhibitors (NRTI), non-nucleoside RT inhibitors (NNRTI), and protease (PR) inhibitors (PI)).

DRMs conferring NRTI and NNRTI resistance occur in RT codons 1-335, whereas DRMs conferring protease inhibitors (PI) resistance occur within PR codons 1-99, based on standard HXB2 numbering. These regions of HIV-1 pol also contain a number of putative CTL epitopes. If these CTL epitopes remain immunogenic after incorporating drug resistance mutations, the well-documented constraints on drug resistance mutations could potentially be exploited to prime the immune system in anticipation of emerging mutants. Similarly, if epitopes incorporating drug resistance mutations exhibit enhanced CTL immunogenicity, then possibly the selection of mutations by ART could modulate the CTL response against HIV.

To explore these connections, we investigated how DRM and CTL pressure overlap to select for specific mutations in HIV-1 subtype C from South India. We studied the PR and RT sequences of 45 patients, who were receiving second-line ART therapy, to investigate how a number of common antiretroviral drug resistance mutations in HIV pol affect CTL recognition with relation to a predefined specific HLA allele-derived peptide.

It is necessary to understand South Indian HIV-1 patient HLA profiles to understand the influence of the CTL epitopes generated against the HIV-1 subtype C drug-resistant mutants.

Prevalence of HIV drug resistance mutations in HIV type 1 isolates in antiretroviral therapy-naïve population from northern India

Sinha S, Ahmad H, Shekhar RC, Kumar N, Dar L, Samantaray JC, Sharma SK, Bhargava A, Pandey RM, Mitsuyasu RL, Fahey JL. AIDS Res Treat. 2012; doi: 10.1155/2012/905823. Epub 2012 Mar 15.

Objective: The increased use of antiretroviral therapy (ART) has reduced the morbidity and mortality associated with HIV, adversely leading to the emergence of HIV drug resistance (HIVDR). In this study, we aim to evaluate the prevalence of HIVDR mutations in ART-naive HIV-1 infected patients from northern India. Design: Analysis was performed using ViroSeq genotyping system based on sequencing of entire protease and two-thirds of the reverse transcriptase (RT) region of pol gene. Results: Seventy-three chronic HIV-1-infected ART-naïve patients eligible for first-line ART were enrolled from April 2006 to August 2008. In 68 patients, the DNA was successfully amplified and sequencing was done. Ninety-seven percent of HIV-1 strains belonged to subtype C, and one each to subtype A1 and subtype B. The overall prevalence of primary drug-resistant mutations (DRMs) was 2.9% (2/68, 95% confidence interval (CI), 0.3-10.2%). One patient had a major RT mutation M184V, known to confer resistance to lamivudine, and another had a major protease inhibitor (PI) mutation D30N that imparts resistance to nelfinavir. Conclusion: Our study shows that primary HIVDR mutations have a prevalence of 2.9% among ART-naive chronic HIV-1-infected individuals.

Prevalence of HIV drug resistance mutation in the northern Indian population after failure of the first-line antiretroviral therapy

Sinha S, Shekhar RC, Ahmad H, Kumar N, Samantaray JC, Sreenivas V, Khan NH, Mitsuyasu RT. Current HIV Research. 2012;10:532-8.

There is limited information available about the prevalence and pattern of human immunodeficiency virus (HIV) drug resistance mutations (DRMs) among antiretroviral therapy (ART)-experienced patients from northern India.

Results of genotypic drug resistance testing were obtained from plasma samples of 128 patients, who had presented with clinical or immunological failure to treatment after at least 6 months of ART. Major DRMs associated with any of the three classes of antiretroviral (ARV) drugs, nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), and protease inhibitors (PI) were seen in 120 out of 128 patients (93.8% prevalence). NRTI and NNRTI DRMs were each seen in 115/128 (89.8%) patients, with M184V, M41L, D67N, and T215Y being the most frequent among NRTI-associated mutations, and K103N, G190A, Y181C, and A98G among NNRTI-associated ones. PI DRMs were observed in 14/128 (10.9%) patients, with L10I, V82A, and L89V being the commonest.

These results present a high prevalence of DRMs among ART-experienced patients from northern India with clinical or immunological failure of therapy. It emphasizes the need for regular testing of plasma samples of such patients for DRMs in order to detect and replace a failing regimen early, and also the use of HIV drug resistance genotyping of ART-naive individuals prior to initiating first-line ART for possible transmitted resistance. It is very important to enhance the access of patients to ARV drugs so that their compliance could be improved and hence development of DRMs be minimized.

Viremia and HIV-1 drug resistance mutations among patients receiving second-line highly active antiretroviral therapy in Chennai, southern India

Saravanan S, Vidya M, Balakrishnan P, Kantor R, Solomon SS, Katzenstein D, Kumarasamy N, Yeptomi T, Sivamalar S, Rifkin S, Mayer KH, Solomon S. Clin Infect Dis. 2012;54:995-1000.

Background: A cross-sectional study among individuals receiving second-line antiretroviral treatment was conducted to report on the level of detectable viremia and the types of drug resistance mutations among those with detectable human immunodeficiency virus (HIV) type 1 plasma viral loads (PVLs). Methods: PVLs were measured using Abbott m2000rt real-time polymerase chain reaction, and genotyping was performed with the ViroSeq genotyping system, version 2.0, and ViroSeq analysis software, version 2.8. Results: Of the 107 patient plasma specimens consecutively analyzed, 30 (28%) had undetectable PVLs (<150 copies/ml) and 77 (72%) were viremic with a median PVL of 5450 copies/ml (interquartile range, 169-1 997 967). Sequencing was done for 107 samples with PVLs >2000 copies/ml: 33 patients (73%) had one of the protease (PR) inhibitor mutations; 41 (91%) had nucleoside reverse-transcriptase inhibitor (NRTI) mutations; 33 (73%) had non-NRTI (NNRTI) mutations; and 30 (66.7%) had both NRTI and NNRTI mutations. Triple-class resistance to NRTIs, NNRTIs, and PR inhibitors was observed in 24 (53%) patients. Based on the mutational profiles observed, all 45 sequences were susceptible to Darunavir and Tipranavir, whereas 47% showed resistance to Lopinavir, 58% showed resistance to Atazanavir, and >60% showed resistance to Saquinavir, Indinavir, Nelfinavir, and Fosamprenavir. Conclusions: The results of the study showed that the majority of patients receiving second-line antiretroviral therapy started to accumulate PR resistance mutations, and the mutation profiles suggest that Darunavir might be the drug of choice for third-line regimens in India.

Suboptimal adherence associated with virological failure and resistance mutations to first-line highly active antiretroviral therapy (HAART) in Bangalore, India

Ekstrand ML, Shet A, Chandy S, Singh G, Shamsundar R, Madhavan V, Saravanan S, Heylen E, Kumarasamy N. Int Health 2011 ;3:27-34.

This study was conducted to examine the relationship between adherence, viral load (VL), and resistance among the outpatients receiving highly active antiretroviral therapy (HAART) in Bangalore, India. In total, 552 outpatients were recruited and VL testing was conducted for all study participants. HIV-1 genotypic resistance testing was performed for 92 participants with a VL >1000 copies/ml. Interpretation of resistance mutations was performed according to the Stanford database. Past-month adherence and treatment interruptions for >48 h were assessed via self-report. At baseline, 34 participants (6%) reported <95% past-month adherence and 110 (20%) reported a history of >48 h treatment interruptions. Combining the two adherence measures, 22% of participants were classified as "suboptimally adherent." In total, 24% of study participants (n = 132) had a detectable VL. Among the 92 samples sent for resistance testing, 68% had at least one nucleoside reverse transcriptase inhibitor (NRTI) mutation, with M184V being the most common (65%) and with 48% having thymidine analogue mutations. Moreover, 72% had at least one non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation and 23% had three or more NNRTI mutations. Both adherence measures were significantly associated with VL (P < 0.001). Suboptimal adherence was significantly associated with resistance mutations (P < 0.02).

The findings illustrate for the first time the strong association between suboptimal adherence, treatment failure, and drug resistance to first-line HAART in India. The predictive value of standard adherence measures was improved by including treatment interruption data.

The observed mutations can jeopardize future treatment options, especially in the light of limited access to second-line treatments. To develop effective adherence interventions, research is needed to examine culturally specific reasons for treatment interruptions.




 

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