Number of HIV-1 founder variants is determined by the recency of the source partner infection

Villabona-Arenas, Christian Julián; Hall, Matthew; Lythgoe, Katrina A.; Gaffney, Stephen G.; Regoes, Roland R.; Hué, Stéphane; Atkins, Katherine E.

doi:10.1126/science.aba5443

Cited by 12 publications

(18 citation statements)

References 47 publications

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“…Sixth, early onward transmission may limit donor-specific adaptations in the T/F strain and allow it to cause more severe cell count reduction in the recipient. Early transmissions, however, are more common to MSM than HSX 18,20 , in keeping with the greater association of MSM with transmission clusters 17 (Fig. 3; Table S7), and should have led to higher R T/F in MSM than HSX, in contrast to our findings.…”

Section: Resultssupporting

confidence: 77%

Transmitted HIV-1 is more pathogenic in heterosexual individuals than homosexual men

James

Dixit

2020

Preprint

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Transmission bottlenecks introduce selection pressures on HIV-1 that vary substantially with the mode of transmission. Recent studies on small cohorts have suggested that stronger selection pressures lead to fitter transmitted/founder (T/F) strains. Manifestations of this selection bias at the population level have remained elusive. Here, we analysed early CD4 cell count measurements reported from ~340,000 infected heterosexual individuals (HSX) and men-who-have-sex-with-men (MSM), across geographies, ethnicities and calendar years and found them to be consistently lower in HSX than MSM (P<0.05). The corresponding average reduction in CD4 counts relative to healthy adults was 86.5% in HSX and 67.8% in MSM (P<0.0001). This difference could not be attributed to differences in age, HIV-1 subtype, viral load, gender, ethnicity, time of transmission, or diagnosis delay across the groups. We concluded that the different selection pressures arising from the different predominant transmission modes have resulted in more pathogenic T/F strains in HSX than MSM.

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Section: Resultssupporting

confidence: 77%

Transmitted HIV-1 is more pathogenic in heterosexual individuals than homosexual men

James

Dixit

2020

Preprint

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“…This should be investigated further in a larger sample size. In addition, the probability of HIV transmission per unprotected sexual contact is closely related to the donor’s viral load [ 50 , 58 – 60 ] and recency of infection with participants with acute HIV infection more likely to transmit multiple transmitted/founder variants [ 61 , 62 ]Thus, differences in risk behavior, routes of virus transmission (receptive vs insertive anal intercourse), clinical stage of and viral load of the source of infection, and presence of STI in recipient may have also influenced the numbers of viruses transmitted and therefore subsequent disease natural history. These factors when in concert with the well-known vulnerability of the thin simple columnar epithelium that lines the rectal mucosal surface as a site of entry [ 63 , 64 ] suggest that multivariant infections may be a result of both biological and social disadvantages.…”

Section: Discussionmentioning

confidence: 99%

Infection with multiple HIV-1 founder variants is associated with lower viral replicative capacity, faster CD4+ T cell decline and increased immune activation during acute infection

et al. 2020

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HIV-1 transmission is associated with a severe bottleneck in which a limited number of variants from a pool of genetically diverse quasispecies establishes infection. The IAVI protocol C cohort of discordant couples, female sex workers, other heterosexuals and men who have sex with men (MSM) present varying risks of HIV infection, diverse HIV-1 subtypes and represent a unique opportunity to characterize transmitted/founder viruses (TF) where disease outcome is known. To identify the TF, the HIV-1 repertoire of 38 MSM participants' samples was sequenced close to transmission (median 21 days post infection, IQR 18-41) and assessment of multivariant infection done. Patient derived gag genes were cloned into an NL4.3 provirus to generate chimeric viruses which were characterized for replicative capacity (RC). Finally, an evaluation of how the TF virus predicted disease progression and modified the immune response at both acute and chronic HIV-1 infection was done. There was higher prevalence of multivariant infection compared with previously described heterosexual cohorts. A link was identified between multivariant infection and replicative capacity conferred by gag, whereby TF gag tended to be of lower replicative capacity in multivariant infection (p = 0.02) suggesting an overall lowering of fitness requirements during infection with multiple variants. Notwithstanding, multivariant infection was associated with rapid CD4 + T cell decline and perturbances in the CD4 + T cell and B cell compartments compared to single variant infection, which were reversible upon control of viremia. Strategies aimed at identifying and mitigating multivariant infection could contribute toward improving HIV-1 prognosis and this may involve strategies that tighten the stringency of the transmission

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“…This accords with the finding that about half of all HIV transmission occurs from an individual in the acute phase [ 4 ]. Furthermore, a recent phylogenetic study of HIV-1 transmission pairs shows that more founder variants of HIV-1 are transmitted during acute infection than during chronic infection [ 17 ]. This suggests that hosts are especially infectious during this early period of infection.…”

Section: Our Hypothesis and Supporting Datamentioning

confidence: 99%

Does HIV infection increase male sexual behavior?

Starks

Kelsey

Rosania

et al. 2020

Evolution, Medicine, and Public Health

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After 40 years of intense study on HIV/AIDS, scientists have identified, amongst other things, at risk populations, stages of disease progression, and treatment strategies. What has received less attention is the possibility that infection might elicit an increase in sexual behavior in humans. In 2000, Starks and colleagues speculated that HIV infection could alter host behavior in a manner that facilitated the spread of the virus. Retrospective and self-report data from five studies now support this hypothesis. Individuals with acute – versus nonacute – stage infections report more sexual partners and more frequent risky sex. Additionally, male sexual behavior increases non-linearly with HIV viral load, and data suggest a potential threshold viral level above which individuals are more likely to engage in risky sexual behavior. Taken together, these data suggest that HIV infection influences male sexual behavior in a manner beneficial to the virus. Here, we present these findings, highlight their limitations, and discuss alternative perspectives. We argue for increased testing of this hypothesis and advocate for increased public health measures to mitigate the putative impact on male sexual behavior. Lay Summary In 2000, Starks and colleagues speculated that HIV infection could alter host behavior in a manner that facilitated the spread of the virus. Retrospective and self-report data from five studies now support this hypothesis. We argue for increased testing of this hypothesis and advocate for increased public health measures to mitigate the putative impact on male sexual behavior.

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Number of HIV-1 founder variants is determined by the recency of the source partner infection

Cited by 12 publications

References 47 publications

Transmitted HIV-1 is more pathogenic in heterosexual individuals than homosexual men

Transmitted HIV-1 is more pathogenic in heterosexual individuals than homosexual men

Infection with multiple HIV-1 founder variants is associated with lower viral replicative capacity, faster CD4+ T cell decline and increased immune activation during acute infection

Does HIV infection increase male sexual behavior?

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