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Try out PMC Labs and tell us what you think. Learn More. Sexual intercourse is a dyadic activity, and intentions to engage in safe sex vary across partners. Because pregnant and newly parenting adolescents and young adults are at high risk for sexually transmitted infections STIsit is important to understand sexual decision-making in this population. Perceiving a partner as having a history of more risk behaviors trended towards a negative relationship with condom use intentions and monogamy intentions. For females, more sex partners related negatively to condom use intentions and positively to monogamy intentions.

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Learn More. Table S3. Table S4. Inferred substitutions along transmission branches for pairs A, E, and F panel A and along pretransmission branches for all pairs A to K panel B. Table S5. Marginal likelihoods, estimated as the harmonic mean of the sampled likelihoods in Bayesian MCMC analysis. Maximum likelihood phylogenetic tree of viral sequences from a source who infected multiple partners at two independent time points. Although it is known that most HIV-1 infections worldwide result from exposure to virus in semen, it has not yet been established whether transmitted strains originate as RNA virions in seminal plasma or as integrated proviral DNA in infected seminal leukocytes.

We Connecticut ab people sex phylogenetic evidence that among six transmitting pairs of men who have sex with men, blood plasma virus in the recipient is consistently more closely related to the seminal plasma virus in the source. All sequences were subtype B, and the env C2V3 of transmitted variants tended to have higher mean isoelectric points, contain potential N-linked glycosylation sites, and favor CCR5 co-receptor usage.

A statistically robust phylogenetically corrected analysis did not detect genetic atures reliably associated with transmission, but further investigation of larger samples of transmitting pairs holds promise for determining which structural and genetic features of viral genomes are associated with transmission. Although individuals may be exposed to HIV through contact with virus in many bodily fluids, most HIV infections worldwide result from sexual transmission of virus harbored in semen 1.

Ancestry-specific and sex-specific risk alleles identified in a genome-wide gene-by-alcohol dependence interaction study of risky sexual behaviors

Infection after sexual exposure has been associated with the viral lo in blood 2 and seminal plasma 3stage of infection of the source partner 4concurrent sexually transmitted infections STIs 5sexual positioning 6and other behavioral and biological factors 78.

Viral genetics likely influence the transmissibility of HIV from semen, as certain sequence features may confer selective advantage for occupying the male genital tract or effectively establishing infection in susceptible individuals 9 It remains unclear whether cell-free virions, cell-associated proviruses, or both are the source reservoir for sexually transmitted HIV One possible mechanism of transmission is that a seminal lymphocyte or macrophage carrying replication-competent provirus cell-associated HIV DNA releases its viral Connecticut ab people sex after entering the recipient partner.

This hypothesis is supported by documented cases of HIV transmission from a source partner receiving suppressive antiretroviral therapy 14 and also by finding multiple related viral variants in the blood of acutely infected individuals 15 An alternative hypothesis is that cell-free virus, measured as HIV RNA in seminal plasma, is the source of transmitted virus, which is supported by the monoclonal acute infections found in most studies 1718 and the positive correlation between blood plasma HIV RNA concentrations and transmission risk 23.

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Finally, both mechanisms might occur naturally 13with one route predominating for undetermined reasons. Separately evolving subpopulations of HIV are frequently established in diverse tissues, including the lung 19central nervous system, spleen 20and male genital tract 921after infection. This anatomic compartmentalization is a result of selection by local factors such as differential immune responses, drug concentrations, and tissue tropism Conserved, compartment-specific genetic motifs of the env -coding region have been found in viral subpopulations from the semen 9 and the blood of acutely infected individuals 18 Putative genetic correlates of sexual transmission in the gene coding for envelope glycoprotein env have also been reported 102425 ; however, there is little concordance between the studies, which suggests that such correlates are too complex to be evinced from currently available samples.

Here, we report on the genetic and structural elements of the C2V3 region of env extracted from the blood and semen of subjects belonging to a transmission cohort of recently infected men who have sex with men MSM. Epidemiological linkage analysis confirmed HIV transmission between the identified source and recipient for each pair.

Perception of partner sexual history: effects on safe-sex intentions

Recipient partners provided biological samples an average of 72 days after their EDI, and all reported having engaged in receptive anal intercourse with their source partners. In four pairs, source partners had been infected with HIV for less than 6 months at the time of HIV transmission, and the remaining two source partners A and F were chronically infected.

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Comparisons within and between partner pairs. Average is mean for ages and laboratory values, except as indicated below. The origin of transmitted virus and degree of differentiation of viral subpopulations within source partners was inferred using phylogenetic and population genetic methods see Materials and Methods.

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All sequences were of subtype B and did not show evidence for superinfection within hosts. Additionally, the estimated time to the most recent common ancestor T MRCA for recipient blood and source seminal plasma HIV-1 RNA sequences was less than that for recipient blood plasma and source seminal cell HIV-1 DNA sequences table S2further indicating that the transmitted viral subpopulations were not derived from archived provirus A to F Phylogenetic analysis of source and recipient viral sequences.

Maximum likelihood phylogenies of viral subpopulations in anatomic compartments for each transmission pair A to F, Table 1. Differentiation of the three viral subpopulations was evident within all source individuals to varying degrees Fig. Viral subpopulations sampled from blood plasma and seminal plasma within source patients were admixed for transmission pairs B to E Fig.

The sequenced C2V3 region of cell-free transmitted virus had, on average, a higher mean isoelectric point median, 9. However, because clonally derived sequences are unlikely to constitute independent samples from the viral population, the P values reported above are likely to overestimate the statistical ificance of differences.

All sequences were, on average, subject to purifying selection for all transmission pairs. Six sites were inferred to be positive selection in two of the six transmission pairs A and F; table S3 and fig.

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S3but these sites were not shared across transmission pairs fig. For all but one of the transmission pairs Cthe genetic algorithm approach 27 for adaptively mapping selective regimes to lineages failed to reject a model in which selection was homogeneous across the phylogeny. This result might be artifactual given the overall low diversity in this transmission pair samples were obtained less than 30 days after the EDI; Table 1thus limiting reliability in the estimate of the synonymous mutation rate in some lineages.

We also attempted to associate specific sequence motifs with transmitted viral variants while ing for the shared ancestry of viruses sampled from transmission pairs.

The origins of sexually transmitted hiv among men who have sex with men

We reconstructed unobserved ancestral viral strains using maximum likelihood and mapped substitutions to transmission and pretransmission branches see Supplementary Material ; Fig. Only one codon position of HXB2 env shared a substitution between two transmission pairs QR and QK; table S4A along a transmission branch, and one codon position of HXB2 env had substitutions in five of six cases along a pretransmission branch table S4B.

In a sample of six transmission pairs with three recipient partners sharing a common source partner, it is not surprising that no shared transmission motifs were detected. The robust identification of ature motifs in the context of HIV transmission remains an open statistical problem, exacerbated by the similarity of sequences due to shared ancestry rather than positive selection and Connecticut ab people sex need to for founder effects when attempting to identify conserved motifs The hypothesis that sexually transmitted HIV originates in the seminal plasma of the source partner is the most likely mechanism of transmission according to our sequence analyses, but we should consider other possible mechanisms.

First, it is possible that all six HIV transmissions occurred during anal sex, with the insertive recipient partner having been exposed to HIV present in the blood of the receptive source partner for example, through tears in his rectal mucosa, instead of virus in his semen. If we further assume that viral RNA subpopulations in blood and seminal plasma of each of the source partners are closely related and distinct from the cell-associated seminal HIV DNAthen phylogenetic analyses may be congruent with the patterns seen in Fig.

However, at least in one transmission pair pair Aa clear distinction between blood- and semen-derived HIV RNA sequences was detected in the source partner, and the transmitted virus was more similar to the latter. The probability of this scenario is further reduced by the observations 6 that the rates of HIV transmission during anal sex are much lower when the source partner Connecticut ab people sex the receptive partner rather than the insertive partner, and that the receptive partner is more likely to be exposed to virus in semen than virus in blood.

These data also suggest that the HIV RNA population in the blood could be the source of the HIV RNA population in semen, and this finding may be important in the role of antiretroviral therapy to reduce the infectiousness of a potential source partner.

Second, discrepant viral lo in blood and seminal biological samples necessitated the use of different sequence amplification techniques single-genome amplification for blood and clonal amplification for semenwhich could have biased the composition of each sample. However, we used the same set of polymerase chain reaction PCR primers for all samples to reduce amplification bias, and such a bias would be expected to generate phylogenetic clustering based on the amplification technique that is, clonally amplified semen sequences would cluster together and separately from the single-genome amplified blood sequenceswhich was not observed Fig.

Third, the sample of sequences of HIV DNA generated from seminal cells could be biased toward the subpopulation of infected seminal cells containing archived and mostly replication-incompetent provirus Although we cannot eliminate the possibility that unsampled, low-frequency, cell-associated HIV DNA founded the transmitted viral population, it is unlikely to have occurred in all transmission pairs, especially given the high degree of genetic similarity and phylogenetic clustering between the HIV RNA subpopulations sampled from the blood plasma of recipient partners and the seminal plasma of source partners.

Fourth, observations reported in this study are based on the C2V3-coding region of envand alternative may have been obtained if other coding regions were investigated. This region of envhowever, has been widely used in studies concerning HIV transmissions, and its choice allows for the identification of important viral characteristics including cellular tropism and infectivity after sexual exposure 9101823 Fifth, the relatively small of transmission pairs studied limits the broad generalization of these findings to all Connecticut ab people sex exposures; therefore, larger investigations are needed to confirm our findings with a high degree of statistical confidence.

Because of the clear importance of identifying genetic correlates of transmissibility for the purposes of guiding preventive efforts, we examined sequence attributes that have ly been associated with transmission 23 — Whereas mean isoelectric points, s of putative N-linked glycosylation sites, and co-receptor tropism differed between the transmitted and the nontransmitted viral subpopulations, we were unable to identify specific motifs or substitutions associated with the sexual transmission of HIV from semen among six transmission pairs of MSM.

Such motifs are probably too subtle to deduce because of sample size limitations inherent in this and other studies of HIV transmission 23 — However, although larger studies are warranted, this study identifies HIV RNA populations in the seminal plasma as an attractive target for biological efforts to interrupt transmission.

All were interviewed for sexual histories, examined, and administered HIV counseling. Samples of urine, blood, and semen were obtained. After 48 hours of abstinence, semen was collected by masturbation without lubricant.

Neisseria gonorrhoeae and Chlamydia trachomatis infection was assessed in urine samples LabCorp.

Syphilis infection was assessed by rapid plasma reagin titers. ViroSeq v. Sequences were manually checked with Sequencher 4. Sequence characteristics were as follows: co-receptor utilization determined with WebPSSM 36potential N-linked glycosylation sites identified with a custom script within HyPhy 37HIV-1 subtype determined as described by Kosakovsky Pond et al.

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Epidemiological linkage confirmation was performed on pol sequences from each partner Codons associated with drug resistance were removed to evaluate transmission linkage independent of resistance mutations Linkage were not disclosed to participants. Gene flow between compartments blood, seminal plasma, and seminal cell within source individuals and between source compartments and recipient blood plasma was estimated with F st 45and statistical ificance was assessed with permutations.

Models of DNA substitution and coalescent demographics were compared with Bayes factors.

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Transmission pairs with low diversity Fig. Pair F was excluded because the EDI could not be reliably determined. We investigated selection by means of codon models 48 A genetic algorithm was used to map selection classes to lineages Model selection was used to select a DNA substitution model, and evidence for recombination was evaluated with GARD 50and analyses were implemented with Datamonkey Author contributions: D.

Competing interests: D. The other authors have no competing interests.

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National Center for Biotechnology InformationU. Sci Transl Med. Author manuscript; available in PMC Feb 1. David M. Butler1 Wayne Delport1 Sergei L. Kosakovsky Pond1 Malcolm K. Little1 Douglas D. Richman1, 2 and Davey M. Sergei L. Kosakovsky Pond.

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