While changes in gut microbial populations have been described in human immuno-deficiency virus (HIV)-infected patients undergoing antiretroviral therapy (ART), the mechanisms underlying the contributions of gut bacteria and their molecular agents (metabolites and proteins) to immune recovery remain unexplored. To study this, we examined the active fraction of the gut microbiome, through examining protein synthesis and accumulation of metabolites inside gut bacteria and in the bloodstream, in 8 healthy controls and 29 HIV-infected individuals (6 being longitudinally studied). We found that HIV infection is associated to dramatic changes in the active set of gut bacteria simultaneously altering the metabolic outcomes. Effects were accentuated among immunological ART responders, regardless diet, subject characteristics, clinical variables other than immune recovery, the duration and type of ART and sexual preferences. The effect was found at quantitative levels of several molecular agents and active bacteria which were herein identified and whose abundance correlated with HIV immune pathogenesis markers. Although, we cannot rule out the possibility that some changes are partially a random consequence of the disease status, our data suggest that most likely reduced inflammation and immune recovery is a joint solution orchestrated by both the active fraction of the gut microbiota and the host.
Elite controllers (EC) represent a small subset of HIV-1-infected people that spontaneously control viral replication. However, natural virological suppression and absence of immune dysfunction are not always long-term sustained. We define exceptional EC (EEC) as HIV-1 subjects who maintain the EC characteristics without disease progression for more than 25 years. We analyzed three EEC, diagnosed between 1988 and 1992, who never showed signs of clinical disease progression in absence of any antiretroviral treatment. A comprehensive clinical, virological, and immunological study was performed. The individuals simultaneously exhibited ≥3 described host protective alleles, low levels of total HIV-1 DNA (<20 copies/10 6 CD4 + t-cells) without evidence of replication-competent viruses (<0.025 IUPM), consistent with high levels of defective genomes, strong cellular HIV-1-specific immune response, and a high poly-functionality index (>0.50). Inflammation levels of EEC were similar to HIV-1 negative donors. Remarkably, they showed an exceptional lack of viral evolution and 8-fold lower genetic diversity (<0.01 s/n) in env gene than other EC. We postulate that these EEC represent cases of spontaneous functional HIV-1 cure. A non-functional and non-genetically evolving viral reservoir along with an HIV-1-specific immune response seems to be key for the spontaneous functional cure. The use of combination antiretroviral therapy (ART) results in sustained undetectable plasma viremia in HIV-1-infected individuals. The success of ART led to initial optimism that HIV-1 may be cured by ART alone; however subsequent studies indicating that such a cure may take as long as 70 years 1,2 led researchers to attempt complementary strategies to reduce viral persistence and potentially facilitate HIV-1 remission 3. However, this has proven extremely difficult to achieve because it entails the eradication of any infectious viral form from the body. This has only putatively been achieved so far in two individuals, the Berlin and London patients 4,5. A less stringent objective, known as functional cure, consists in the permanent suppression of HIV-1 viral replication in the absence of ART even if full viral eradication is not achieved 6 .
Background The preventive effect which tenofovir/emtricitabine could have against SARS-CoV-2 in HIV-negative people is unknown. The objective of this study was to analyse the seroprevalence and clinical manifestations of COVID-19 among users of PrEP, TDF/FTC or TAF/FTC, and to compare it to that of a control group. Methods Observational descriptive study of the seroprevalence of antibodies for SARS-CoV-2 among men who have sex with men and transgender women without use of PrEP(Group1;n=250) and PrEP users with TDF/FTC(n=409) or TAF/FTC(n=91) (Group2;n=500), conducted from 11-May-2020 to 27-Jun-2020. All were provided with a structured questionnaire which collected information on the variables to be analysed and testing for IgG antibodies to SARS-CoV-2 (CMIA) was then carried out. Results The seroprevalence of SARS-CoV-2 was 9·2%(95% CI: 5·9-13·5) in the group without PrEP and 15.0%(95% CI: 12·0-18·4) in the group with PrEP(p=0·026). Among users of TDF/FTC it was 14.7%(95% CI: 11·4-18·5) and in users of TAF/FTC it was 16·5%(95% CI: 9·5-25·7)(p=0·661). In those positive for SARS-CoV-2 receiving PrEP, 57·4% manifested symptoms compared to 78·3% in the control group (p=0·070). In users of TDF/FTC the figure was 53·3% and TAF/FTC 73·3%(p=0·100). The duration of symptoms was 11·5 days in the control group, 9·0 in PrEP users(p=0·116), 7·0 in users of TDF/FTC and 13·0 in users of TAF/FTC(p = 0·100). Conclusion Users of PrEP, TDF/FTC or TAF/FTC presented a higher seroprevalence to SARS-CoV-2 than the control group. No statistically significant differences were found in relation to clinical manifestations. PrEP users should use the same prevention measures as those indicated for the general population.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.