Impact of Acute HIV Infection and Early Antiretroviral Therapy on the Human Gut Microbiome

Abstract Background Intestinal microbial dysbiosis is evident in chronic HIV-infected individuals and may underlie inflammation that persists even during antiretroviral therapy (ART). It remains unclear, however, how early after HIV infection gut dysbiosis emerges and how it is affected by early ART. Methods Fecal microbiota were studied by 16s rDNA sequencing in 52 Thai men who have sex with men (MSM), at diagnosis of acute HIV infection (AHI), Fiebig Stages 1–5 (F1-5), and after 6 months of ART initiation, and in 7 Thai MSM HIV-uninfected controls. Dysbiotic bacterial taxa were associated with relevant inflammatory markers. Results Fecal microbiota profiling of AHI pre-ART vs HIV-uninfected controls showed a mild dysbiosis. Transition from F1-3 of acute infection was characterized by enrichment in pro-inflammatory bacteria. Lower proportions of Bacteroidetes and higher frequencies of Proteobacteria and Fusobacteria members were observed post-ART compared with pre-ART. Fusobacteria members were positively correlated with levels of soluble CD14 in AHI post-ART. Conclusions Evidence of gut dysbiosis was observed during early acute HIV infection and was partially restored upon early ART initiation. The association of dysbiotic bacterial taxa with inflammatory markers suggests that a potential relationship between altered gut microbiota and systemic inflammation may also be established during AHI.

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Very Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz030 ◽

2019 ◽

Vol 220 (12) ◽

pp. 1885-1891 ◽

Cited By ~ 8

Author(s):

Joanna Hellmuth ◽

Bonnie M Slike ◽

Carlo Sacdalan ◽

John Best ◽

Eugene Kroon ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Antiretroviral Therapy ◽

Hiv Infection ◽

Immune Activation ◽

Acute Hiv Infection ◽

Activation Markers ◽

Art Initiation ◽

Markers Of Inflammation ◽

Median Plasma ◽

Acute Hiv

Abstract Background Chronic immune activation in the blood and central nervous system is a consequence of human immunodeficiency virus (HIV) infection that contributes to disease morbidity and can occur despite virally suppressive antiretroviral therapy (ART). The trajectory of HIV-related inflammation may vary with the timing of ART initiation. We examined immune activation markers in cerebrospinal fluid (CSF) and blood specimens collected over 96 weeks from participants who initiated ART during acute HIV infection (AHI). Methods RV254/SEARCH010 study participants with AHI underwent CSF (n = 89) and plasma (n = 146) sampling before initiating ART and at weeks 24 and 96 of treatment. A majority participants (64.4%) received a standard ART regimen (hereafter, “standard ART”), with some (34.7%) also receiving maraviroc and raltegravir for the first 24 weeks (hereafter, “ART plus”). We compared neopterin, CXCL10, CCL2, and interleukin 6 (IL-6) levels in the AHI group to those in 18 healthy, uninfected controls. Results Following 24 and 96 weeks of treatment, levels of all CSF markers normalized while levels of several plasma markers remained elevated in the AHI group (P < .001). Participants receiving the ART-plus regimen had lower median plasma CCL2 levels at week 24 and lower plasma neopterin levels at week 96. Conclusions ART initiation during AHI differentially impacts the brain compartment, with markers of inflammation returning to normal levels in the CSF, where they were sustained at week 96, but not in plasma.

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Antiretroviral Therapy for Acute HIV Infection

Case Medical Research ◽

10.31525/ct1-nct03877536 ◽

2019 ◽

Author(s):

Keyword(s):

Antiretroviral Therapy ◽

Hiv Infection ◽

Acute Hiv Infection ◽

Acute Hiv

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Viral Dynamics of Acute HIV-1 Infection

Journal of Experimental Medicine ◽

10.1084/jem.190.6.841 ◽

1999 ◽

Vol 190 (6) ◽

pp. 841-850 ◽

Cited By ~ 186

Author(s):

Susan J. Little ◽

Angela R. McLean ◽

Celsa A. Spina ◽

Douglas D. Richman ◽

Diane V. Havlir

Keyword(s):

Antiretroviral Therapy ◽

Hiv Infection ◽

Doubling Time ◽

Basic Reproductive Number ◽

Reproductive Number ◽

Target Cells ◽

Viral Dynamics ◽

Acute Hiv Infection ◽

Acute Hiv ◽

The Mean

Viral dynamics were intensively investigated in eight patients with acute HIV infection to define the earliest rates of change in plasma HIV RNA before and after the start of antiretroviral therapy. We report the first estimates of the basic reproductive number (R0), the number of cells infected by the progeny of an infected cell during its lifetime when target cells are not depleted. The mean initial viral doubling time was 10 h, and the peak of viremia occurred 21 d after reported HIV exposure. The spontaneous rate of decline (α) was highly variable among individuals. The phase 1 viral decay rate (δI = 0.3/day) in subjects initiating potent antiretroviral therapy during acute HIV infection was similar to estimates from treated subjects with chronic HIV infection. The doubling time in two subjects who discontinued antiretroviral therapy was almost five times slower than during acute infection. The mean basic reproductive number (R0) of 19.3 during the logarithmic growth phase of primary HIV infection suggested that a vaccine or postexposure prophylaxis of at least 95% efficacy would be needed to extinguish productive viral infection in the absence of drug resistance or viral latency. These measurements provide a basis for comparison of vaccine and other strategies and support the validity of the simian immunodeficiency virus macaque model of acute HIV infection.

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Efficacy, pharmacokinetics and neurocognitive performance of dual, NRTI-sparing antiretroviral therapy in acute HIV-infection

AIDS ◽

10.1097/qad.0000000000002652 ◽

2020 ◽

Vol 34 (13) ◽

pp. 1923-1931

Author(s):

Cynthia L. Gay ◽

Dayna T. Neo ◽

Aaron S. Devanathan ◽

Joann D. Kuruc ◽

Kara S. McGee ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Hiv Infection ◽

Neurocognitive Performance ◽

Acute Hiv Infection ◽

Acute Hiv

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Abundant HIV-infected cells in blood and tissues are rapidly cleared upon ART initiation during acute HIV infection

Science Translational Medicine ◽

10.1126/scitranslmed.aav3491 ◽

2020 ◽

Vol 12 (533) ◽

pp. eaav3491 ◽

Cited By ~ 11

Author(s):

Louise Leyre ◽

Eugène Kroon ◽

Claire Vandergeeten ◽

Carlo Sacdalan ◽

Donn J. Colby ◽

...

Keyword(s):

Hiv Infection ◽

Stage Iv ◽

T Cell Subsets ◽

Viral Reservoir ◽

Lymphoid Tissues ◽

Acute Hiv Infection ◽

Tissue Samples ◽

Art Initiation ◽

Acute Hiv ◽

Infected Cells

The timing and location of the establishment of the viral reservoir during acute HIV infection remain unclear. Using longitudinal blood and tissue samples obtained from HIV-infected individuals at the earliest stage of infection, we demonstrate that frequencies of infected cells reach maximal values in gut-associated lymphoid tissue and lymph nodes as early as Fiebig stage II, before seroconversion. Both tissues displayed higher frequencies of infected cells than blood until Fiebig stage III, after which infected cells were equally distributed in all compartments examined. Initiation of antiretroviral therapy (ART) at Fiebig stages I to III led to a profound decrease in the frequency of infected cells to nearly undetectable level in all compartments. The rare infected cells that persisted were preferentially found in the lymphoid tissues. Initiation of ART at later stages (Fiebig stages IV/V and chronic infection) induced only a modest reduction in the frequency of infected cells. Quantification of HIV DNA in memory CD4+ T cell subsets confirmed the unstable nature of most of the infected cells at Fiebig stages I to III and the emergence of persistently infected cells during the transition to Fiebig stage IV. Our results indicate that although a large pool of cells is infected during acute HIV infection, most of these early targets are rapidly cleared upon ART initiation. Therefore, infected cells present after peak viremia have a greater ability to persist.

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Efficacy of NNRTI-based antiretroviral therapy initiated during acute HIV infection

AIDS ◽

10.1097/qad.0b013e3283463c07 ◽

2011 ◽

pp. 1 ◽

Cited By ~ 1

Author(s):

Cynthia L Gay ◽

Ashley J Mayo ◽

Chelu K Mfalila ◽

Haitao Chu ◽

Anna C Barry ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Hiv Infection ◽

Acute Hiv Infection ◽

Acute Hiv

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Normalization of Soluble CD163 Levels After Institution of Antiretroviral Therapy During Acute HIV Infection Tracks with Fewer Neurological Abnormalities

The Journal of Infectious Diseases ◽

10.1093/infdis/jiy337 ◽

2018 ◽

Vol 218 (9) ◽

pp. 1453-1463 ◽

Cited By ~ 14

Author(s):

Michelle L D’Antoni ◽

Mary Margaret Byron ◽

Phillip Chan ◽

Napapon Sailasuta ◽

Carlo Sacdalan ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Hiv Infection ◽

Acute Hiv Infection ◽

Soluble Cd163 ◽

Neurological Abnormalities ◽

Acute Hiv

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Decreased Seroreactivity in Individuals Initiating Antiretroviral Therapy during Acute HIV Infection

Journal of Clinical Microbiology ◽

10.1128/jcm.00757-19 ◽

2019 ◽

Vol 57 (10) ◽

Cited By ~ 10

Author(s):

Mark M. Manak ◽

Linda L. Jagodzinski ◽

Ashley Shutt ◽

Jennifer A. Malia ◽

Mike Leos ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Hiv Infection ◽

Western Blot ◽

Research Collaboration ◽

Virologic Suppression ◽

Infection Status ◽

Acute Hiv Infection ◽

Western Blot Assay ◽

Acute Hiv ◽

Hiv 1

ABSTRACTAntiretroviral therapy (ART) during acute HIV infection (AHI) interrupts viral dynamics and may delay the emergence of serological markers targeted by current HIV screening and confirmatory assays, thus creating challenges for correctly classifying HIV infection status. The performance of three HIV antigen/antibody combination (HIV Ag/Ab Combo) assays (the Bio-Rad GS, Abbott Architect, and Bio-Rad BioPlex 2200 assays) was evaluated with samples collected from RV254/South East Asia Research Collaboration in HIV 010 (RV254/SEARCH010) study (Bangkok, Thailand) participants at weeks 12 and 24 following the initiation of ART at Fiebig stage I (FI) (n = 23), FII (n = 39), or FIII/IV (n = 22). Supplemental, confirmatory testing was performed by the Geenius HIV 1/2 and HIV-1 Western blot assays (Bio-Rad). Samples from 30 untreated, HIV-1-infected individuals demonstrated robust HIV Ag/Ab Combo assay reactivity with well-developed HIV-1 Western blotting profiles by 24 weeks after infection. In contrast, 52.2% of samples from individuals initiating ART at FI, 7.7% of samples from individuals initiating ART at FII, and 4.5% of samples from individuals initiating ART at FIII/IV were nonreactive by the HIV Ag/Ab Combo assays, with 36.4 to 39.1% of samples having low signal-to-cutoff (S/CO) results by the Architect and BioPlex assays (S/CO < 10). Seroreversion from a reactive to a nonreactive status was observed in 10 individuals initiating ART at FII and 3 individuals initiating ART at FIII/IV. The Geenius and HIV-1 Western blot assay results were negative or indeterminate for 73.9% and 69.6% of individuals, respectively, treated at FI; 50.0% and 26.3% of individuals, respectively, treated at FII; and 54.5% and 40.9% of individuals, respectively, treated at FIII/IV. Virologic suppression of HIV-1 by ART during AHI impedes seroconversion to biomarkers of infection, limiting the utility of HIV Ag/Ab Combo and supplemental, confirmatory assays for infection status determination.

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