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HIV-1 Infection Alters the Viral Composition of Plasma in Men Who Have Sex with Men.

ABSTRACT: Altered gut virome and expanded abundance of certain viruses were found in HIV-1-infected individuals. It remains largely unknown how plasma virus composition changes during HIV-1 infection and antiretroviral therapy (ART). We performed viral metagenomic analysis on viral particles enriched from human plasma from 101 men who have sex with men (MSM) with or without HIV-1 infection and whether or not on ART and compared the differences in the plasma virome. An increased plasma viral abundance of main eukaryotic viruses was observed during HIV-1 infection in MSM, especially in AIDS patients (CD4⁺ T cell counts of <200). Anellovirus, pegivirus and hepatitis B virus (HBV) were the most abundant blood-borne viruses detected among MSM and HIV-1-infected individuals, and anellovirus and pegivirus were closely related to HIV-1 infection. High diversity of anelloviruses was found mostly in HIV-1-infected MSM, and their abundance was positively correlated with the HIV-1 viral load, but negatively correlated with both CD4⁺ T cell counts and CD4⁺/CD8⁺ ratio; in contrast, the abundance of pegivirus showed opposite correlations. ART usage could restore the plasma virome toward that of HIV-1-negative individuals. These data showed an expansion in abundance of certain viruses during HIV-1 infection, indicating the higher risk of shedding some blood-borne viruses in these individuals. These investigations indicate that both anellovirus and pegivirus may play certain roles in HIV disease progression.IMPORTANCE Though an increasing number of studies have indicated the existence of an interaction between the virome and human health or disease, the specific role of these plasma viral components remains largely unsolved. We provide evidence here that an altered plasma virome profile is associated with different immune status of HIV-1 infection. Specific resident viruses, such as anellovirus and pegivirus, may directly or indirectly participate in the disease progression of HIV-1 infection. These results can help to determine their clinical relevance and design potential therapies.

SUBMITTER: Liu K

PROVIDER: S-EPMC8103983 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPrevious studies estimating the fraction of transmissions from persons with primary HIV have not focused on the effects of switching sex role in male homosexual populations. Such behavioral fluctuations can increase the contribution of primary HIV in the overall population.MethodsWe modeled HIV transmission with 8 compartments defined by 4 behavioral groups, with different anal-insertive and anal-receptive combinations, and 2 stages of infection. We explored the effects of fluctuating behavioral categories on endemic prevalence and the fraction of transmissions from primary HIV. We varied transition rates to develop the theory on how behavioral fluctuation affects infection patterns, and we used the transition rates in a Netherlands cohort to assess overall effects in a real setting.ResultsThe dynamics of change in behavior-group status over time observed in the Netherlands cohort amplifies the prevalence of infection and the fraction of transmissions from primary HIV, resulting in the highest proportions of transmissions being from people with primary HIV. Fluctuation between dual- or receptive-role periods and no-anal-sex periods mainly determines this amplification. In terms of the total transmissions, the dual-role risk group is dominant. Fluctuation between insertive and receptive roles decreases the fraction of transmissions from primary HIV, but such fluctuation is infrequently observed.ConclusionThe fraction of transmissions from primary HIV is considerably raised by fluctuations in insertive and receptive anal sex behaviors. This increase occurs even when primary HIV or later infection status does not influence risk behavior. Thus, it is not simply biology but also behavior patterns and social contexts that determine the fraction of transmissions from primary HIV. Moreover, each primary HIV transmission has a larger population effect than each later infection transmission because the men to whom one transmits from primary HIV carry on more chains of transmissions than the men to whom one transmits later in infection. Reducing transmissions from primary HIV should be a primary focus of HIV control efforts.

Project description:OBJECTIVE:HIV continues to be a global and national public health challenge, and men who have sex with men (MSM) are disproportionately affected in the USA. Transmission of HIV is intentional if the person living with HIV knows about his/her serostatus, acts with the intention to and actually transmits HIV. Research on intentional transmission of HIV infections is lacking, and the relationships between perceived intentional transmission, viral suppression and psychosocial outcomes have not been assessed. The objective of this study was to investigate the association between perceived intentional transmission of HIV, sustained viral suppression and psychosocial outcomes. METHODS:Data were obtained from 338 MSM living with HIV who participated in a disclosure intervention study. Logistic and linear regression models were used to assess the associations between perceived intentional transmission and viral suppression, condomless anal intercourse in the past 30 days, being at risk for clinical depression, substance use, self-efficacies for condom use, HIV disclosure and negotiation of safer sex practices, and sexual compulsivity. RESULTS:44% of the study population reported perceiving intentional HIV transmission. After adjusting for sociodemographic characteristics, men who thought that they were infected intentionally had 69% higher odds (adjusted OR: 1.69; 95%?CI 1.01 to 2.83) of being at risk for clinical depression, and on average, scored approximately 3 points and 4 points higher on depressive symptoms and sexual compulsivity, respectively (adjusted ?: 3.29; 95%?CI 0.42 to 6.15; adjusted ?: 3.74; 95%?CI 1.32 to 6.17) compared with men who did not think that they were intentionally infected. After adjusting for confounders, there was no statistically significant association between perceived intentional transmission and viral suppression. CONCLUSIONS:Intervention programmes for MSM living with HIV who thought they were infected intentionally are warranted and should aim to attenuate depressive symptoms and sexual compulsivity.

Project description:Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5' and 3' half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3-6 days before symptom onset and 14-17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized.

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HIV-1 Infection Alters the Viral Composition of Plasma in Men Who Have Sex with Men.

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