Higher Frequency of HIV-1 Drug Resistance and Increased Nucleoside Reverse Transcriptase Inhibitor Mutations among the HIV-1 Positive Antiretroviral Therapy-Naïve patients Coinfected With Mycobacterium tuberculosis Compared With Only HIV Infection in India

Abstract

Background: Emergence of human immunodeficiency virus (HIV) drug resistance mutations prior to highly active antiretroviral therapy is a serious problem in clinical management of HIV/AIDS. Risk factors for appearance of drug resistance mutations are not known. We hypothesize that Mycobacterium tuberculosis infection may contribute to rapid emergence of such mutations in antiretroviral therapy-naïve patients.

Methods: A total of 115 patients were recruited in this study of which 75 were HIV+TB+ coinfected (group 1) and 40 were HIV+TB- (group 2). Blood samples from all the patients were collected and CD4+ cell counts; HIV-1 plasma viral load and sequencing of protease and two-third region of reverse transcriptase of HIV-1 was performed and analyzed for drug resistance pattern.

Results: For patients with HIV+TB+, 10.6% (8/75) had mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs), 4% (3/75) to nucleoside reverse transcriptase inhibitors, and only 2.6% (2/75) patients had mutations to protease inhibitors. Interestingly, for group 2 (HIV+TB-), there were only NNRTI mutations found among these patients, and only 3 patients (7.5%) had these drug-resistant mutations. Clade typing and phylogenetic tree analysis showed HIV-1 subtype C predominance in these patients.

Conclusions: Our study showed that higher percentage of HIV drug resistance mutations was found among HIV+TB+ individuals compared with tuberculosis-uninfected patients. Tuberculosis coinfection may be a risk factor for emergence of high frequency of drug resistance mutations. Studies with a larger sample size will help to confirm these findings from the Indian population.

Keywords: HIV; HIV drug resistance mutations; NNRTI; NRTI; PI; TB coinfection; antiretroviral therapy.

Figure 1.

Phylogenetic trees of (A) HIV+TB+ ART-naïve and (B) HIV+TB− ART-naïve samples. 1302-bp DNA sequences of PI and RT regions from HIV-1 were analyzed and aligned with reference sequences from different subtypes. GeneBank accession number and corresponding subtypes of reference sequences are given. KF716467, AY795906, AY563169, and AF286233 are subtype C; AF061642 is subtype G; AF005496 is subtype H; KC797225 is subtype B; K03454 is subtype D; DQ189088 and AF077336 are subtype F. FJ670523 and DQ676872 are subtype A; GU237072 is subtype J and L20571 and L20587 are subtype O. ART indicates antiretroviral therapy; PI, protease inhibitor; RT, reverse transcription.