The inference of HIV-1 transmission direction between HIV-1 positive couples based on the sequences of HIV-1 quasi-species

Abstract

Background To infer transmission direction of a HIV transmission chain is helpful not only in legal jurisdiction but also in precise intervention to prevent HIV spread. Recently, the direction of transmission is inferred by whether paraphyletic-monophyletic (PM) or a combination of paraphyletic and polyphyletic (PP) topologies is observed or not between the sequences of source and recipient in the phylogenetic tree. However, paraphyly between them often declines over time and may disappear between spouses due to bidirectional transmission after primary infection. In this study, our aim is to test the reliability of inferring HIV transmission direction between epidemiologically linked HIV-1 positive couples using whether or not paraphyly is observed in phylogenetic tree. Methods HIV quasi-species were sequenced using PCR product clones, and then Bayesian analysis of molecular sequences with MCMC was employed to construct phylogenetic relationship of env, gag, pol gene fragments of HIV-1 positive couples using BEAST software. Results Our results showed that all sequences of seven couples except pol sequences of couple 12 and 13 form their own monophyletic cluster in phylogenetic tree including the closest control sequences from GenBank or other studies on local samples, which are supported by significant Bayesian posterior probabilities more than 0.9932. Of seven couples, paraphyly is only observed in phylogenetic tree constructed with env and po l gene sequences of three couples and gag gene sequences of four couples. Paraphyly is not observed in half of HIV positive couples. Pol sequences of couple 13 is separated by Blast selected controls; pol sequences of couple 12 in phylogenetic tree is supported by a lower Bayesian posterior value. Conclusion Paraphyly relationship between sequences of donator and recipient is only observed among partial HIV-1 positive couples with epidemiological link. Phylogenetic relationship is not always the same when various gene regions of HIV are used to conduct phylogenetic analysis. The combination of phylogenetic analysis based on various gene regions of HIV and enough epidemiology investigation is essential when inferring transmission direction of HIV in a transmission chain or in one couple. However, while observed paraphyly can be used to infer transmission direction in HIV-1 positive couple, no observed paraphyly cannot deny it.

Using phylogenetics to infer HIV-1 transmission direction between known transmission pairs

“…There is a noticeable drop in discriminatory power when our models only include readily obtainable information, and thus, our results confirm that inferences about directionality entail considerable uncertainty in the absence of key epidemiological information ( 37 ). Moreover, because the stage of the transmitting partner’s infection is likely to influence the topology class of the phylogenetic tree, which in turn, influences the probability of correctly identifying the transmitting partner, chronic-stage transmitters who are more likely to exhibit PM topologies are thus more likely to be correctly identified ( 8 ).…”

Using Phylogenetics to Infer Hiv-1 Transmission Direction Between Known Transmission Pairs

“…Indeed, two variables that are not typically known and are not included under our real-life conditions model-the recency of the transmitter's infection at the time of transmission and the time from transmission-have been shown to influence the topology class (8,9), which in turn influences the chance of correctly identifying the transmitting partner. In the absence of such data, our results confirm that inferences about directionality can entail considerable uncertainty (31). Nonetheless, our results shed light into the possible reasons for variability between studies.…”

Health related behaviors among HIV-infected people who are successfully linked to care: an institutional-based cross-sectional study

“…Research has shown that unhealthy lifestyles including smoking, lack of physical exercise and substance abuse put PLWHA at an increased rate of disease progression, opportunistic infections and chronic obstructive pulmonary diseases [6][7][8][9]. In additional, risky sexual behaviors among HIV positive people put their partners at risk for HIV infection and other sexually transmitted infections [10][11][12]. Moreover, the success of the "treatment as prevention" model also requires interventions that provide PLWHA the necessary skills to develop and sustain health-promoting behaviors including healthy sexual behaviors [13,14].…”