Genital Inflammation Predicts HIV-1 Shedding Independent of Plasma Viral Load and Systemic Inflammation
1Division of Human Biology and 2Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 USA 3Departments of Medicine 4Global Health 5Biostatistics, and 6Epidemiology, University of Washington, Seattle, WA 98195 USA 7Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya 8Coast General Hospital, Mombasa, Kenya.JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 08/2012; 61(4). DOI: 10.1097/QAI.0b013e31826c2edd
In women, genital HIV-1 RNA levels predict the risk of HIV-1 transmission independent of plasma viral load. To better understand the factors that contribute to genital HIV-1 shedding, we evaluated the relationships between genital and plasma cytokine concentrations and HIV-1 RNA levels. Vaginal, but not plasma, levels of interferon gamma-induced protein 10 (IP-10) were significantly associated with vaginal viral load, independent of plasma viral load. Thus, efforts to decrease HIV-1 transmission must take into account the role of local inflammation, which is not necessarily reflected in plasma measurements.
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ABSTRACT: We conducted a prospective cohort study of HIV-positive men ages 18-35 years in Kisumu, Kenya to determine if medical circumcision of ART-naïve HIV-positive men leads to increased viral load and penile viral shedding. From 108 HIV-positive men circumcised by forceps guided method and followed-up weekly for six weeks, 29 were evaluated for penile viral shedding. HIV-1 RNA was measured in plasma from 19 men and in penile lavage samples from 29 men. Samples were collected before circumcision and at weekly intervals for six weeks or until the circumcision wound was healed. CD4+ t-cell counts from 102 HIV-positive men were determined at baseline and at 2 weeks thereafter. Wounds with healthy scar, no scab or opening and no suture tracks were deemed healed. Among 65 ART-naive men, mean CD4+t-cell count increased from 417 cells/mm at baseline to 456 cells/ mm after 2 weeks (p= 0.04), but did not change in the 37 men on ART (p=0.81). There was no change in HIV plasma viral load ( p=0.36), but penile viral shedding rose significantly within one week after circumcision then declined to undetectable levels by 6 weeks (MANOVA; p<0.001). In 28 of 29 men (96.6%), there was no detectable viral shedding after certification of wound healing. Medical circumcision among ART-naïve HIV-infected men results in a transitory rise in penile viral shedding before complete wound healing, which should pose no additional risk of HIV transmission if men adhere to six weeks post-circumcision sexual abstinence and use condoms consistently.
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ABSTRACT: It has been hypothesized that immune activation and inflammation may increase HIV-1 susceptibility and that cytokines may be useful biomarkers for risk. Within a prospective cohort, we conducted a nested case-control analysis of plasma cytokine levels among women who acquired HIV-1 <3 months after sampling, compared to three different control groups. We observed associations between lower IL-6 and IL-10 and higher IL-7 levels with HIV-1 acquisition, however these associations were inconsistent when comparing to different control groups. Inconsistent results within our study and among prior studies suggest that reproducible findings are needed before cytokines are useful biomarkers for HIV-1 susceptibility.
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