Antiretroviral Therapy Down-Regulates Innate Antiviral Response Genes in Patients With AIDS in Sub-Saharan Africa

Boulware, David R.; Meya, David B.; Bergemann, Tracy L.; Williams, Darlisha A; Louis, Irina Vlasova-St.; Rhein, Joshua; Staddon, Jack H.; Kambugu, Andrew; Janoff, Edward N.; Bohjanen, Paul R.

doi:10.1097/qai.0b013e3181ef4963

Cited by 25 publications

(28 citation statements)

References 59 publications

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“…We detected increased expression of A3G in acute infection in oral and blood samples, which persisted in untreated infection but remained at control levels in ART-treated animals. A study examining ART-responsive genes in HIV infected individuals also showed that CXCL10 and A3G expression is abrogated after successful ART 57 .…”

Section: Discussionmentioning

confidence: 99%

Characterization of Peripheral and Mucosal Immune Responses In Rhesus Macaques on Long-Term Tenofovir and Emtricitabine Combination Antiretroviral Therapy

Jasny

Geer²,

Frank³

et al. 2012

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background The goal of antiretroviral therapy (ART) is to suppress virus replication to limit immune system damage. Some have proposed combining ART with immune therapies to boost antiviral immunity. For this to be successful, ART must not impair physiological immune function. Methods We studied the impact of ART (tenofovir and emtricitabine) on systemic and mucosal immunity in uninfected and SIV-infected Chinese rhesus macaques. Subcutaneous ART was initiated 2 weeks after tonsillar inoculation with SIVmac239. Results There was no evidence of immune dysregulation as a result of ART in either infected or uninfected animals. Early virus-induced alterations in circulating immune cell populations (decreased central memory T cells and myeloid dendritic cells) were detected, but normalized shortly after ART initiation. ART-treated animals showed marginal SIV-specific T cell responses during treatment, which increased after ART discontinuation. Elevated expression of CXCL10 in oral, rectal and blood samples and APOBEC3G mRNA in oral and rectal tissues was observed during acute infection and was down-regulated after starting ART. ART did not impact the ability of the animals to respond to tonsillar application of polyICLC with increased CXCL10 expression in oral fluids and CD80 expression on blood myeloid dendritic cells. Conclusion Early initiation of ART prevented virus induced damage and did not impede mucosal or systemic immune functions.

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Section: Discussionmentioning

confidence: 99%

Characterization of Peripheral and Mucosal Immune Responses In Rhesus Macaques on Long-Term Tenofovir and Emtricitabine Combination Antiretroviral Therapy

Jasny

Geer²,

Frank³

et al. 2012

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Antiretroviral therapy (ART) exposure in utero and in the perinatal period may also impact immune development. In adults, ART is associated with anemia, neutropenia, relative lymphopenia and down regulation of select pattern recognition receptor genes 39-42 . However, there are currently no data measuring the effect of ART exposure on functional innate immune ontogeny early in life.…”

Section: Discussionmentioning

confidence: 99%

Altered Innate Immune Development in HIV-Exposed Uninfected Infants

Reikie¹,

Adams²,

Leligdowicz³

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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BACKGROUND Early in life HIV-exposed uninfected (HEU) infants are at an increased risk of morbidity and mortality from infectious disease compared to HIV-unexposed (UE) infants. To improve our understanding of the mechanisms underlying their increased risk, we contrasted innate immune development between HEU and UE infants in a developing world setting, where early-life infectious disease risk is exceptionally high. METHODS A prospective longitudinal cohort of HEU and UE newborns was established and the most detailed characterization to date of HEU infant immune development was performed. Single-cell cytokine production was analyzed by flow cytometry after stimulation of whole blood with pathogen associated molecular patterns (PAMP). RESULTS Monocyte, classical dendritic cell and plasmacytoid dendritic cell composition was similar between HEU and UE infants throughout the first year of life. However, HEU mononuclear cells mounted an enhanced pro-inflammatory response to PAMP stimulation, both in quantity of cytokine produced per-cell and in proportion of responder cells. Significant differences in cytokine production were detected on the single cell level in a PAMP-specific pattern, but only at 2 and 6 weeks of age; all differences normalized by 12 months of age. CONCLUSIONS This time course of innate immune deviation early in life corresponds to the clinical window of vulnerability to infections in HEU infants and may be at least partially responsible for their increased morbidity and mortality from infectious disease.

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“…From May 2006 until December 2013, HIV-infected persons with CD4<200 cells/ μ l who had either no active opportunistic infection at time of initiating ART or cryptococcal meningitis were enrolled as described previously. 12–16 Cryptococcal meningitis was diagnosed by cerebrospinal fluid (CSF) cryptococcal antigen (IMMY Inc., Norman OK) and/or quantitative fungal culture. 13,14 The IMMY Inc. latex agglutination text was used prior to 2012, whereas the LFA was used after this point.…”

Section: Methodsmentioning

confidence: 99%

Seroprevalence of histoplasmosis in Kampala, Uganda

Bahr¹,

Sarosi²,

Meya³

et al. 2015

Med. Myco.

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Histoplasmosis is endemic to the Midwestern United States, but cases have been reported nearly worldwide. A 1970 study found 3.8% skin test sensitivity to Histoplasma capsulatum in Uganda but no systemic study of histoplasmosis exposure has occurred since the onset of the human immunodeficiency virus (HIV) pandemic. This study investigated the seroprevalence of H. capsulatum and sought previously undetected cases of histoplasmosis in Kampala, Uganda. Serum, cerebrospinal fluid (CSF) and/or urine specimens were obtained from HIV-infected persons with suspected meningitis. Specimens were tested for H. capsulatum IgG and IgM by enzyme immune assay and Histoplasma antigen. 147 of the 257 subjects who were enrolled had cryptococcal meningitis. Overall, 1.3% (2/151) of subjects were serum Histoplasma IgG positive, and zero of 151 were IgM positive. Antigen was not detected in any serum (n = 57), urine (n = 37, or CSF (n = 63) samples. Both subjects with serum Histoplasma IgG positivity had cryptococcal meningitis. Histoplasma capsulatum IgG was detected at low levels in persons with HIV/AIDS in Kampala, Uganda. Histoplasmosis is not widespread in Uganda but micro-foci do exist. There appears to be no cross-reactivity between Cryptococcus neoformans and Histoplasma antigen testing, and cryptococcosis appears to be at most, a rare cause of positive Histoplasma IgG.

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Antiretroviral Therapy Down-Regulates Innate Antiviral Response Genes in Patients With AIDS in Sub-Saharan Africa

Cited by 25 publications

References 59 publications

Characterization of Peripheral and Mucosal Immune Responses In Rhesus Macaques on Long-Term Tenofovir and Emtricitabine Combination Antiretroviral Therapy

Characterization of Peripheral and Mucosal Immune Responses In Rhesus Macaques on Long-Term Tenofovir and Emtricitabine Combination Antiretroviral Therapy

Altered Innate Immune Development in HIV-Exposed Uninfected Infants

Seroprevalence of histoplasmosis in Kampala, Uganda

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