Phylogenetic Characterization of HIV-1 Sub-Subtype A1 in Karachi, Pakistan

Abstract

(1) Background: HIV-1 sub-subtype A1 is common in parts of Africa, Russia, former Soviet Union countries, and Eastern Europe. In Pakistan, sub-subtype A1 is the predominant HIV-1 subtype. Preliminary evidence suggests that distinct strains of HIV-1 sub-subtype A1 are circulating in Pakistan; however, an in-depth molecular phylogenetic characterization of HIV-1 sub-subtype A1 strains in Pakistan have not been presented. We performed a detailed characterization of the HIV-1 sub-subtype A1 epidemic in Pakistan using state-of-the-art molecular epidemiology and phylodynamics. (2) Methods: A total of 143 HIV-1 sub-subtype A1 gag sequences, including 61 sequences generated specifically for this study from PLHIVs part of our cohort, representing all sub-subtype A1 gag sequences from Pakistan, were analyzed. Maximum-likelihood phylogenetic cluster analysis was used to determine the relationship between Pakistani sub-subtype A1 strains and pandemic sub-subtype A1 strains. Furthermore, we used signature variation, charge distribution, selection pressures, and epitope prediction analyses to characterize variations unique to Pakistani HIV-1 strains and establish the association between signature variations and Gag epitope profile. (3) Results: The HIV-1 sub-subtype A1 sequences from Pakistan formed three main clusters: two that clustered with Kenyan sequences (7 and 10 sequences, respectively) and one that formed a Pakistan-specific cluster of 123 sequences that were much less related to other sub-subtype A1 sequences available in the database. The sequences in the Pakistan-specific cluster and the Kenyan reference strains exhibited several signature variations, especially at amino acid positions 312, 319, 331, 372, 373, 383, and 402. Structural protein modeling suggested that amino acid changes in these positions result in alterations of the Gag protein structure as well as in Gag-specific T-cell epitopes. (4) Conclusions: Our results suggest that the majority of the Pakistan HIV-1 sub-subtype A1 strains were unique to Pakistan and with a specific mutation pattern in Gag.

Identification of a novel first-generation HIV-1 circulating recombinant form (CRF152_DG) among people living with HIV in Karachi, Pakistan

“…Meanwhile, HIV-1 prevalence among men who have sex with men (MSM) has also increased (11%), making them another key HIV population group in Karachi ( 15 ). Previous studies have identified sub-subtype A1, CRF02_AG, CRF35_A1D, C, D, and G clades circulating among key HIV populations in Karachi ( 7 , 16 ).…”

“…Pakistan has reported a 78.5% increase in new HIV infections in the last decade ( https://www.aidsdatahub.org ). Currently, 210,000 people are registered in different HIV treatment centers across the country ( 7 ). In Pakistan, the HIV-1 genetic diversity is becoming increasingly complex, with sub-subtype A1 and CRF02_AG being the most predominant clades responsible for approximately 68.1% and 16.5% of HIV-1 infections ( 8 , 9 ).…”

Evaluation of the Training Program to Train HIV Treatment Center Staff in Pakistan

“…However, HIV exists as a concentrated epidemic in key population groups such as people who inject drugs, transgender sex workers, male sex workers, men who have sex with men, and female sex workers, where the prevalence is approximately 38.4%, 7.5%, 5.6%, 5.4%, and 2.2%, respectively [2,3]. Furthermore, the number of new cases has increased rapidly in the past 10 years, and several new outbreaks have occurred in Pakistan in recent years, including the 2019 HIV outbreak in Larkana, where more than 1,000 children were found infected with HIV [2][3][4][5][6][7][8][9].…”