Research Article: Prevalence of HIV Drug Resistance Mutations in HIV Type 1 Isolates in Antiretroviral Therapy Naïve Population from Northern India

Date Published: March 15, 2012

Publisher: Hindawi Publishing Corporation

Author(s): S. Sinha, H. Ahmad, R. C. Shekhar, N. Kumar, L. Dar, J. C. Samantaray, S. K. Sharma, A. Bhargava, R. M. Pandey, R. L. Mitsuyasu, J. L. Fahey.


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 DNA was successfully amplified and sequencing was done. 97% of HIV-1 strains belonged to subtype C, and one each to subtype A1 and subtype B. The overall prevalence of primary 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.

Partial Text

The national antiretroviral therapy (ART) program in India for treatment of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) was started by National AIDS Control Organization (NACO), Ministry of Health and Family Welfare, Government of India, in April 2004. By the end of November 2009, more than 2, 50,000 patients infected with HIV had received ART under the program [1]. As per the latest report by Joint United Nations programe on HIV/AIDS (UNAIDS), prevalence of HIV in India is estimated to be 0.31%, that translates to approximately 2.31 million persons living with HIV/AIDS [2]. The current standard first-line treatment for HIV in India consists of two nucleoside reverse transcriptase inhibitors (NRTIs), zidovudine or stavudine plus lamivudine, and one nonnucleoside reverse transcriptase inhibitor (NNRTI), nevirapine or efavirenz. Regimens with protease inhibitors (PIs) are available as second-line treatment options upon failure of the first-line ART under the national program. As per the time trends for evolution of primary HIVDR suggested by Grant et al., it can be expected that the prevalence of drug resistance mutations (DRMs) may soon increase in India [3, 4]. The widespread use of ART has resulted in an increased prevalence of drug-resistant HIV strains, ranging from 10% to 20% among drug-naive patients in other countries [5–7]. The emergence HIVDR is inevitable, given the high replication and mutation rates of HIV, and the necessity for lifelong ART, which may not always be available to HIV-infected individuals in resource-limited settings, due to multitude of practical and logistic barriers. The genetic diversity of HIV-1 originates from rapid viral replication in infected individuals with a high rate of incorrect nucleotide substitutions in the viral genome. DRMs result from selective pressure during viral replication, especially in the presence of subtherapeutic levels of ART [8, 9].

A total of 73 patients were recruited into the study. Genotyping was possible in plasma samples from 68 (93%) of the participants. Five samples failed PCR amplification, of which 3 had viral load below 1000 copies/mL, and for the remaining two, reasons were unknown. Of the study participants, 91.2% gave a history of heterosexual exposure, 4.4% had bisexual behavior, and the rest did not reveal their HIV exposure history. Subtype C was found to be the most predominant subtype (97%) in our population (Table 1 and Figure 1). The median age of the study group was 35 years (range: 20–55 years). The median CD4 count was 107 cells/μL (range: 49–157cells/μL), and the median plasma HIV RNA load was 223640 copies/mL (5.34 log10), range: 8264 (4.98 log10)–750000 (5.75 log10).

This is the first study sponsored by NACO for estimation of HIVDR mutation in ART-naïve population from northern India. Its results reveal overall prevalence of primary HIVDR to be 2.9% (CI, 0.3%–10.2%) in this region. As per WHO guidelines, the drug-resistance prevalence in a geographical area has been categorized into <5%, 5–15% and >15% [23]. This classification signifies the level of HIVDR surveillance programs required for monitoring primary HIVDR. An earlier study done by Chaturbhuj et al. [24] in 2010 has shown that the presence of surveillance DRMs in ART-naïve HIV-1-infected individuals recruited from Voluntary Centre for Testing and Counselling (VCTC) was less than the WHO threshold of 5%. Our data fits in the WHO low zone of (<5%), suggesting that primary HIV drug resistance is still under the limits in northern India, nevertheless there is a need for more data on primary drug resistance in ART naïve individuals.   Source: