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The Effect of Antiretroviral Therapy Initiation on the Vaginal Microbiome in HIV-Infected Women.

ABSTRACT: Background:The impact of antiretroviral therapy (ART) initiation on the vaginal microbiome is unknown. This is of particular importance among women living in sub-Saharan Africa. Understanding this relationship could help elucidate if and how the host immune system interacts with the vaginal microbiome. Methods:The vaginal microbiome of HIV-1/HSV-2-coinfected women (n = 92) in Uganda was evaluated from self-collected vaginal swabs 1 month pre-ART and at 4 and 6 months post-ART initiation. The vaginal microbiome was characterized by 16S rRNA gene-based sequencing and quantitative polymerase chain reaction. Vaginal community state types (CSTs) were identified using proportional abundance data. Changes in microbiome composition were assessed with permutational analyses of variance (PerMANOVA). Results:Five vaginal CSTs were identified, which varied significantly by bacterial load (P < .01): CST-1 was characterized by Lactobacillus iners, CST-2 by Gardnerella, CST-3 by Gardnerella and Prevotella, CST-4 by Lactobacillus crispatus, and CST-5 was highly diverse. Vaginal microbiome composition also did not change significantly after ART initiation (P = .985). Immune reconstitution after ART initiation did not affect vaginal microbiome CST assignment (P = .722) or individual-level changes in bacterial load (log response ratio [interquartile range], -0.50 [-2.75 to 0.38] vs -0.29 [-2.03 to 1.42]; P = .40). Conclusions:The vaginal microbiome of HIV-infected women was not affected by the initiation of ART or immune reconstitution in this observational study. Further research is needed to explore the long-term effects of ART treatment on the vaginal microbiome.

SUBMITTER: Liu CM

PROVIDER: S-EPMC6798248 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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The Effect of Antiretroviral Therapy Initiation on the Vaginal Microbiome in HIV-Infected Women.

Liu Cindy M CM Packman Zoe R ZR Abraham Alison G AG Serwadda David M DM Nalugoda Fred F Aziz Maliha M Prodger Jessica L JL Kaul Rupert R Kalibbala Sarah S Gray Ronald H RH Price Lance B LB Quinn Thomas C TC Tobian Aaron Ar AA Reynolds Steven J SJ

Open forum infectious diseases 20190712 9

<h4>Background</h4>The impact of antiretroviral therapy (ART) initiation on the vaginal microbiome is unknown. This is of particular importance among women living in sub-Saharan Africa. Understanding this relationship could help elucidate if and how the host immune system interacts with the vaginal microbiome.<h4>Methods</h4>The vaginal microbiome of HIV-1/HSV-2-coinfected women (n = 92) in Uganda was evaluated from self-collected vaginal swabs 1 month pre-ART and at 4 and 6 months post-ART init ...[more]

PMID: 31660406

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Project description:Background: The latent viral reservoir is the major obstacle to achieving HIV remission and necessitates life-long antiretroviral therapy (ART) for HIV-infected individuals. Studies in adults and children have found that initiating ART soon after infection is associated with a reduction in the size of the HIV-1 reservoir. Here we quantified cell-associated HIV-1 DNA in early-treated but currently older HIV-infected children suppressed on ART.Methods: The study participants comprised of a cohort of 146 early-treated children with HIV-1 RNA <50 copies/ml enrolled as part of a clinical trial in Johannesburg, South Africa. A stored buffy coat sample collected after a median 4.3 years on ART and where HIV-1 RNA was <50 copies/ml was tested for cell-associated HIV-1 DNA levels. An in-house, semi-nested real-time quantitative hydrolysis probe PCR assay to detect total HIV-1 subtype C proviral DNA was used. Children were followed prospectively for up to 3 years after this measurement to investigate subsequent HIV-1 RNA rebound/failure while remaining on ART. Age at ART initiation, HIV-1 RNA decline prior to HIV-1 DNA measurement and other factors were investigated.Results: A gradient between age at ART initiation and later HIV-1 DNA levels was observed. When ART was started <2 months of age, the lowest levels of cell-associated HIV-1 DNA (median 1.4 log10copies/106 cells, interquartile range [IQR] 0.95-1.55) were observed compared to ART started at 2-4 months (median 1.68, IQR 1.26-1.97) or 5-14 months of age (median1.98, IQR 1.69-2.25). A low CD4 T-cell count pre-treatment predicted higher levels of HIV-1 DNA on later testing. The probability of HIV-1 RNA rebound >50 copies/ml whilst on ART within 3 years after the DNA measurement was 2.07 (95% CI: 1.352-3.167) times greater if the HIV-1 DNA level was above the median of 55 copies/106 cells.Conclusions: Cell-associated HIV-1 DNA levels measured after more than 4 years on ART were lower the younger the age of the child when ART was initiated. This marker of the size of the viral reservoir also predicted subsequent viral rebound/treatment failure while ART was sustained. The results provide additional evidence of the benefits of prompt diagnosis and early ART initiation in newborns and infants.

Project description:Type 2 diabetes mellitus incidence is increased in HIV-infected persons. We examined the associations of diabetes mellitus with known diabetes mellitus-risk alleles from the general population in the context of HIV infection, and explored effect modification by combination antiretroviral therapy (cART).The Women's Interagency HIV Study is a prospective cohort of HIV-infected women. Seventeen European-derived diabetes mellitus-risk polymorphisms were genotyped in the eligible participants of the Women's Interagency HIV Study. Analyses were run separately for non-African Americans (Whites, Hispanics, Asians, and other; n?=?378, 49 with incident diabetes mellitus) and African Americans (n?=?591, 49 with incident diabetes mellitus). Cox proportional-hazards models were fit to estimate hazard ratios for diabetes mellitus overall and within strata of cART.In non-African Americans, heterogeneity across cART regimen was observed for nine of the 14 polymorphisms (phet?<?0.05). One polymorphism was statistically significantly inversely associated with diabetes mellitus risk among women taking two nucleotide reverse transcriptase inhibitors (NRTIs) + non-nucleotide reverse transcriptase inhibitor (NNRTI). Five polymorphisms were statistically significantly associated with diabetes mellitus among women treated with at least two NRTIs?+?at least one protease inhibitor and one polymorphism was associated with diabetes mellitus among those treated with at least three NRTIs?±?NNRTI. The hazard ratio per risk allele for IGF2BP2 rs1470579 was 2.67 (95% confidence interval 1.67-4.31) for women taking cART with at least two NRTIs?+?at least one protease inhibitor and 2.45 (95% confidence interval 1.08-5.53) in women taking at least three NRTIs?±?NNRTI (phet?=?2.50?×?10?³). No such associations were observed in the African Americans.Genetic susceptibility to diabetes mellitus, based on the variants studied, is substantially elevated among HIV-infected women using cART containing three or more NRTI/protease inhibitor components. A personalized medicine approach to cART selection may be indicated for HIV-infected persons carrying these diabetes mellitus-risk variants.

Dataset Information

The Effect of Antiretroviral Therapy Initiation on the Vaginal Microbiome in HIV-Infected Women.

Publications

The Effect of Antiretroviral Therapy Initiation on the Vaginal Microbiome in HIV-Infected Women.

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