Characterization of HIV-1 Epidemic in Kyrgyzstan

Abstract

Kyrgyzstan has one of the highest rates of HIV-1 spread in Central Asia. In this study, we used molecular-epidemiological approaches to examine the HIV-1 epidemic in Kyrgyzstan. Samples were obtained from HIV-positive individuals who visited HIV/AIDS clinics. Partial pol gene sequences were used to identify HIV-1 subtypes and drug resistance mutations (DRMs) and to perform phylogenetic analysis. Genetic diversity and history reconstruction of the major HIV-1 subtypes were explored using BEAST. This study includes an analysis of 555 HIV-positive individuals. The study population was equally represented by men and women aged 1-72 years. Heterosexual transmission was the most frequent, followed by nosocomial infection. Men were more likely to acquire HIV-1 during injection drug use and while getting clinical services, while women were more likely to be infected through sexual contacts (p < 0.01). Heterosexual transmission was the more prevalent among individuals 25-49 years old; individuals over 49 years old were more likely to be persons who inject drugs (PWID). The major HIV-1 variants were CRF02_AG, CRF63_02A, and sub-subtype A6. Major DRMs were detected in 26.9% of the study individuals; 62.2% of those had DRMs to at least two antiretroviral (ARV) drug classes. Phylogenetic analysis revealed a well-defined structure of CRF02_AG, indicating locally evolving sub-epidemics. The lack of well-defined phylogenetic structure was observed for sub-subtype A6. The estimated origin date of CRF02_AG was January 1997; CRF63_02A, April 2004; and A6, June 1995. A rapid evolutionary dynamic of CRF02_AG and A6 among Kyrgyz population since the mid-1990s was observed. We observed the high levels of HIV-1 genetic diversity and drug resistance in the study population. Complex patterns of HIV-1 phylogenetics in Kyrgyzstan were found. This study highlights the importance of molecular-epidemiological analysis for HIV-1 surveillance and treatment implementation to reduce new HIV-1 infections.

Keywords: Central Asia; HIV molecular epidemiology; HIV phylogenetics; Kyrgyzstan; phylodynamic analysis.

FIGURE 1

Maximum-likelihood phylogenetic trees of HIV-1 pol sequences of CRF02_AG/CRF63_02A (A) and sub-subtype A6 (B). Monophyletic clades (A–D) with the branch support ≥ 80 and containing for over 70% of study sequences are shaded in yellow. JAB, Jalal-Abad and Batken provinces; CRF, circulating recombinant form; MSM, men who have sex with men; PWID, persons who inject drugs; DRM, drug resistance mutation.

FIGURE 2

Transmission clusters of study HIV-1 pol sequences ofCRF02_AG/CRF63_02A (A) and sub-subtype A6 (B). Clusters were detected in IQ-TREE at maximum 0.045 genetic distances and 90 branch support thresholds. Each figure (circle/square) corresponds to a node on the phylogenetic tree; figure shape, size, and color correspond to an individual’s gender, age, and HIV-1 transmission mode according to the left center footnote. The line drawn between figures indicates that HIV-1 sequences from the respective individuals in phylogenetic tree fell within the clustering thresholds. The black asterisk indicates the HIV-1 drug resistance; the red asterisk indicates the HIV-1 drug resistance to at least two ARV drug classes. Circles with the bold black border correspond to the pregnant women. The solid oval corresponds to a cluster of three individuals infected by CRF63_02A. The dashed lines divide figures corresponding to individuals from the different study regions. JAB, Jalal-Abad and Batken provinces; MSM, men who have sex with men; PWID, persons who inject drugs.

FIGURE 3

Phylodynamic reconstruction of HIV-1 sCRF02_AG/CRF63_02A (A) and sub-subtype A6 (B) in Kyrgyzstan. (A) The Bayesian Skyline plot was reconstructed for the 325 pol gene sequences of CRF02_AG and 10 sequences of CRF63_02A. The horizontal bold line indicates effective population size through time; blue-shaded area represents the 95% highest posterior density (HPD). The vertical bold black line indicates the estimated origin date for CRF02_AG [January 1997 (95% HPD: February 1986–May 2004)]; the vertical dashed line indicates the estimated origin date for CRF63_02A [April 2004 (95% HPD: January 1997–April 2009)]. (B) The Gaussian Markov random field (GMRF) Bayesian Skyride plot was reconstructed for the 173 pol gene sequences of sub-subtype A6. The horizontal bold line indicates effective population size through time; pink-shaded area represents the 95% HPD. The vertical bold black line indicates the estimated origin date for sub-subtype A6 [June 1995 (95% HPD: August 1985–August 2002)].