HIV Reverse Transcriptase and Protease Genes Variability Can Be a Biomarker Associated with HIV and Hepatitis B or C Coinfection

Abstract

Variability of the HIV reverse transcriptase (RT) and protease (PR) genes has been used as indicators of drug resistance and as a mean to evaluate phylogenetic relationships among circulating virus. However, these studies have been carried in HIV mono-infected populations. The goal of this study was to evaluate, for the first time, the HIV PR and RT sequences from HIV/HBV and HIV/HCV co-infected patients. HIV PR and RT genes were amplificated and sequenced to resistance analysis. The bioinformatics analysis was performed to infer about sequences clustering and molecular evolution. The results showed that the most frequent amino acid substitutions in RT were L214F (67.6%), I135T (55.9%), and in PR was V15I (41.2%). The molecular clock analysis showed that the HIV circulating in co-infected patients were separated in two clusters in the years 1999–2000. Some patients included as HIV mono-infected according patients’ medical records and inside the co-infected cluster were, in fact, co-infected by PCR analysis. Analysis of the decision trees showed susceptibility to lamivudine and emtricitabine were important attribute to characterize co-infected patients. In conclusion, the results obtained in this study suggest, for the first time, that HIV RT and PR genes variability could be a genetic biomarker to coinfection.

Circulation of multiple subtypes (A, G and CRFs 02_AG) of human immunodeficiency virus type 1 (HIV-1) in selected districts of Punjab province, Pakistan

“…Similar observations have been reported in previous studies [23][24][25]. Subtyping of currently prevailing HIV-1 isolates is considered crucial for understanding the genetic evolution of this virus around the globe [26], and, for this particular purpose, the pol gene is considered an important marker for accurate delineation of HIV-1 subtypes [15][16][17][27][28][29]. The amplified region of the pol gene comprised the protease gene (nt 1 to 297) and a part of the reverse transcriptase (RT) gene (nt 1 to 753).…”

Profile of HCV Genotypes and Hiv-Subtypes Among Hiv-Coinfected Patients in Southern Brazil

“…Our study corroborates the results of these studies. In addition, the results of the present study were in accordance with previous investigations, which report that B recombinant and CRFs of HIV-1 circulate among HIV-coinfected patients (12,35) . The detailed dynamics of HIV subtypes viral propagation in the study region is not well understood, although two phylogeographic studies have demonstrated possible routes for the origin and spread of subtype C in the Southern region of the country (36,37) .…”

“…HIV is characterized by high genetic diversity and extensive heterogeneity. This characteristic is due to multiple factors, including multiple human populations, high rates of viral evolution/ recombination, selective pressure of the host immune system and/or antiretroviral therapy (12,33) . Although subtype B has been showing a declining trend in sexual transmission, it still accounts for a large proportion.…”

“…However, there have been a few studies showing the genetic variability of HIV-1 among patients with HIV-hepatitis coinfections. A study in HIV-coinfected patients in Brazil reported that HIV-1 subtype C and B were present in 47.4% and 31.6% of HIV-coinfected patients, respectively (35) ; another Brazilian study reported that HIV-1 subtype B was the most prevalent (12) . Our study corroborates the results of these studies.…”

“…Among HIV-coinfected patients, the presence of a hepatotropic virus can lead to an overload of the host's immune system, which may lead to the emergence of specific HIV variants (12) . However, there is little information on the genetic variability of HIV in HBV-and/or HCV-coinfected patients.…”