Independent introduction of two major HIV-1 genotypes into distinct high-risk populations in Thailand

The RV144 HIV-1 vaccine trial (Thailand, 2003 to 2009), using immunogens genetically matched to the regional epidemic, demonstrated the first evidence of efficacy for an HIV-1 vaccine. Here we studied the molecular evolution of the HIV-1 epidemic from the time of immunogen selection to the execution of the efficacy trial. We studied HIV-1 genetic diversity among 390 volunteers who were deferred from enrollment in RV144 due to preexisting HIV-1 infection using a multiregion hybridization assay, full-genome sequencing, and phylogenetic analyses. The subtype distribution was 91.7% CRF01_AE, 3.5% subtype B, 4.3% B/CRF01_AE recombinants, and 0.5% dual infections. CRF01_AE strains were 31% more diverse than the ones from the 1990s Thai epidemic. Sixty-nine percent of subtype B strains clustered with the cosmopolitan Western B strains. Ninety-three percent of B/CRF01_AE recombinants were unique; recombination breakpoint analysis showed that these strains were highly embedded within the larger network that integrates recombinants from East/Southeast Asia. Compared to Thai sequences from the early 1990s, the distance to the RV144 immunogens increased 52% to 68% for CRF01_AE Env immunogens and 12% to 29% for subtype B immunogens. Forty-three percent to 48% of CRF01_AE sequences differed from the sequence of the vaccine insert in Env variable region 2 positions 169 and 181, which were implicated in vaccine sieve effects in RV144. In conclusion, compared to the molecular picture at the early stages of vaccine development, our results show an overall increase in the genetic complexity of viruses in the Thai epidemic and in the distance to vaccine immunogens, which should be considered at the time of the analysis of the trial results.

mentioning

confidence: 99%

Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

Kijak

Tovanabutra

Rerks-Ngarm

et al. 2013

“…Consequently, only a year later, high HIV prevalence rates of the same subtype were detected among IDUs in Myanmar and the Yunnan province of China (19,30,65). Then, an increase of HIV-1 CRF01_AE infections was detected among female sex workers in Thailand, and soon thereafter, CRF01_AE spread to IDUs, suggesting an early and complicated interconnection between epidemics among drug users and commercial sex workers (49). By 1995, CRF01_AE was widespread among Thai IDUs (20,56), and IDU populations in other countries, such as Vietnam and Malaysia, had experienced rapid increases in CRF01_AE infections (21,43,46).…”

mentioning

confidence: 99%

Unequal Evolutionary Rates in the Human Immunodeficiency Virus Type 1 (HIV-1) Pandemic: the Evolutionary Rate of HIV-1 Slows Down When the Epidemic Rate Increases

Berry

Ribeiro

Kothari

et al. 2007

HIV-1 sequences in intravenous drug user (IDU) networks are highly homogenous even after several years, while this is not observed in most sexual epidemics. To address this disparity, we examined the human immunodeficiency virus type 1 (HIV-1) evolutionary rate on the population level for IDU and heterosexual transmissions. All available HIV-1 env V3 sequences from IDU outbreaks and heterosexual epidemics with known sampling dates were collected from the Los Alamos HIV sequence database. Evolutionary rates were calculated using phylogenetic trees with a t test root optimization of dated samples. The evolutionary rate of HIV-1 subtype A1 was found to be 8.4 times lower in fast spread among IDUs in the former Soviet Union (FSU) than in slow spread among heterosexual individuals in Africa. Mixed epidemics (IDU and heterosexual) showed intermediate evolutionary rates, indicating a combination of fast-and slow-spread patterns. Hence, if transmissions occur repeatedly during the initial stage of host infection, before selective pressures of the immune system have much impact, the rate of HIV-1 evolution on the population level will decrease. Conversely, in slow spread, where HIV-1 evolves under the pressure of the immune system before a donor infects a recipient, the virus evolution at the population level will increase. Epidemiological modeling confirmed that the evolutionary rate of HIV-1 depends on the rate of spread and predicted that the HIV-1 evolutionary rate in a fast-spreading epidemic, e.g., for IDUs in the FSU, will increase as the population becomes saturated with infections and the virus starts to spread to other risk groups.The evolutionary rate of human immunodeficiency virus type 1 (HIV-1) has been shown to differ in different genes as well as in different regions of the same genes. Using molecularclock analyses, the rate of evolution of the env V3 region was estimated to be from 2.3 ϫ 10 Ϫ3 to 6.7 ϫ 10 Ϫ3 substitutions site Ϫ1 year Ϫ1 , while the rate for the whole env was estimated to be between 1.0 ϫ 10 Ϫ3 and 1.7 ϫ 10 Ϫ3 substitutions site Ϫ1 year Ϫ1 (25,26,33,54,63). Stronger diversifying pressure by the immune system on the V3 region is thought to be responsible for the higher rate, while genes, such as gag and pol, that are under less diversifying and more purifying selection pressure show lower rates (25,33,54

“…It is well known that subtype B=, CRF07_BC, CRF08_BC, and CRF01_AE are the major HIV-1 genotypes associated with particular risk populations in China (2,25,26,31). Reports about China in recent years showed that multiple HIV-1 subtypes, including subtype B, CRF01_AE, and CRF07_BC, were coepidemic in the population of MSM (18,32,33).…”

mentioning

confidence: 99%

Reconstituting the Epidemic History of HIV Strain CRF01_AE among Men Who Have Sex with Men (MSM) in Liaoning, Northeastern China: Implications for the Expanding Epidemic among MSM in China

Han

et al. 2012

dHIV CRF01_AE accounted for 84% of the recent infections among men who have sex with men (MSM) in Liaoning Province of northeastern China. CRF01_AE strains were grouped into two distinct clusters (designated clusters 1 and 2) that were also detected in other regions in China. Phylodynamics study revealed that these two CRF01_AE strains were independently introduced into the population of MSM in China in the early and mid-1990s. Our study elucidated unique features of dynamics and interrelationships of MSM epidemics in China.