Socio-demographic and drug use factors associated with HIV-1 recombinants and dual infections in Northern Thai drug users: Associations of risk with genetic complexity
Introduction
Human immunodeficiency virus type 1 (HIV-1) is characterized by extensive and expanding genetic diversity. To date, 9 subtypes within the group M radiation have been described, and many more inter-subtype recombinants have been reported (Kuiken et al., 2009). Recombinant strains are believed to emerge after dual infections within multiply-exposed individuals (Ramos et al., 2002, Taylor et al., 2008). While some of these recombinant strains have been retrieved from only one patient (“unique recombinant forms” or URFs), other recombinants have spread into populations (“circulating recombinant forms” or CRFs) (Taylor et al., 2008). By combining pre-existing beneficial mutations, recombination can accelerate the escape from host immune responses and recent studies suggest that HIV-1 envelope has adapted to evade such responses at population levels (Bunnik et al., 2010). For this reason, HIV dual infection and recombination pose major challenges to vaccine design and can hinder the evaluation of the success of efficacy trials. Dual infection has been associated with accelerated disease progression (reviewed by Smith et al., 2005) and increasing genetic diversity has also been linked to anti-retroviral drug resistance, suggesting that diversity may also play roles in HIV therapeutic outcomes (Djoko et al., 2010). Identifying individuals and sub-groups of populations where dual infections are more frequent and recombinant forms are more likely to arise could help in the design and targeting of preventive interventions aimed at diminishing HIV-1 genetic complexity. Little work has been done on the injection drug use behaviors and practices that might contribute to multiple exposure and dual infection among injecting and non-injecting drug users.
The molecular epidemiology of HIV-1 in Thailand has substantially changed over the past two decades. From the late 1980s until the mid 1990s, HIV-1 strains were segregated by risk group, as subtype B predominated among injecting drug users (IDUs), while CRF01_AE was the major form circulating among those with heterosexual exposure (Subbarao et al., 1998). A change in the proportions of clades was seen in the mid 1990s, when CRF01_AE overtook subtype B among IDUs, while still constituting the major clade being transmitted through heterosexual contact (Tovanabutra et al., 2004, Vanichseni et al., 2001). CRF01_AE was also the predominant clade identified among male sex workers in Northern Thailand (Beyrer et al., 1997). Subsequently, our group reported on the emergence of novel recombinant HIV-1 strains between CRF01_AE and subtype B, which were thought to have emerged in successive rounds of dual infection and transmission among multiply-exposed individuals. By the early 2000s, more than half of new infections among IDUs in Northern Thailand were caused by B/CRF01_AE URFs (Tovanabutra et al., 2004), marking a substantial increase in genetic complexity. Moreover, B/CRF01_AE recombinants were also found in contemporary samples from the general population, and two new CRFs, CRF15_01B (Tovanabutra et al., 2001) and CRF34_01B (Tovanabutra et al., 2007), were found in multiple individuals, some with heterosexual risk factors and some others with IDU risk factors and, presumably, some individuals with dual risks for HIV acquisition and transmission. As the Thai epidemic matured, the emergence of these subtypes confirmed increasing genetic diversity, and also established the bridging of IDU and general population HIV-1 variants at molecular levels. Non-injecting drug users in Thailand predominantly use variants of methamphetamine (Ya Ba, or “crazy medicine”, in Thai), which is generally smoked, not injected. Their demographic and HIV risks vary markedly from IDU and we have previously reported on their lower HIV rates in this cohort (Beyrer et al., 2004).
The Northern region of Thailand, including provinces adjacent to the Golden Triangle in the border with Burma (Myanmar) and Laos, has borne the brunt of the Thai HIV-1 epidemic since its onset. By 2003, this region, that represented only 8% of the country's total population, was home to more than 25% of the AIDS cases (Deewong and Jitnumshap, 2003). The Northern Thai epidemic was marked by both sexual and IDU components, and by the region's extensive commercial sex industry—largely employing sex workers from impoverished Burma, and by high rates of methamphetamine use among adolescents and young adults.
The objective of this study was to evaluate the HIV-1 genetic diversity among sero-positive drug users, both injecting and non-injecting, seeking detoxification at the Chiang Mai Drug Treatment Center (CMDTC), Mae Rim, Thailand, which serves 17 provinces in the northern region. Behavioral and social/demographic variables and drug use practices were investigated for associations with increasing complexity of HIV-1 strains.
Section snippets
Population under study
The Opiate-Users Research (OUR) Study was conducted among 2231 volunteers seeking detoxification at the Chiang Mai Drug Treatment Center (CMDTC), Mae Rim, Thailand. The first phase of the study (February 1999–January 2000) included volunteers admitted for opioid or methamphetamine dependence, and the second phase of the study (February 2000–December 2000) included only IDUs admitted for drug dependence. Inclusion criteria included being 13 years of age or older, provision of informed consent,
Study subjects
Overall 347 of the 2231 participants (15.6%) were HIV-1 sero-positive at the time of enrollment (Table 1). HIV-1 prevalence among those who had ever injected (35.2%, N = 879) was markedly higher than among those who had never injected (2.8%, N = 1352) (OR 18.8, 95% CI 13.2–26.6). There was higher sero-prevalence among men as compared to women (OR 1.7, 95% CI 1.1–2.7). Among male participants, other sociodemographic characteristics statistically significantly associated with increased risk for HIV
Discussion
In this cohort of drug users in Northern Thailand, we show that HIV genetic diversity is increasing and is associated with certain high-risk behaviors and demographic factors. Frequent needle sharing was associated with both dual and recombinant HIV infection. Recent injection of drugs and lower education were significantly associated with dual HIV infection.
Our findings are consistent with several previous studies that show increasing HIV genetic diversity in the Thai IDU population. In our
Role of funding source
This work was partly supported by a cooperative agreement between the Henry M Jackson Foundation for the Advancement of Military Medicine and the U.S. Department of Defense, and partly by grants (1 R01 DA 11133, and a competitive supplement from the Office of AIDS Research) from the National Institutes of Health, Bethesda, MD. The views and opinions expressed herein do not necessarily reflect those of the U.S. Army or of the Department of Defense.
The Henry M Jackson Foundation for the
Contributors
G.H. Kijak, PharmD, PhD: carried out laboratory work and wrote the first draft of the manuscript. C. Beyrer, MD, MPH: Co-principal investigator of project, executed protocol, wrote the first draft of the manuscript. S. Tovanabutra, PhD: Co-principal investigator of project, executed protocol, carried out laboratory work. T. Sripaipan, MPH: carried out statistical analysis. V. Suriyanon, MD: Principal investigator of project. N. Moqueet, MPH: carried out laboratory work. E. Sanders-Buell, MSc:
Conflict of interest
All of the authors declare no conflict of interest.
Acknowledgements
We are thankful to the subjects who participated in this study, Dr. Myat Htoo Razak, Charintarat Kitisri, and the staff of Research Institute for Health Sciences, Northern Drug Treatment Center, Thailand, for their help collecting specimens, epidemiological data, and laboratory technical assistance.
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