Soren Gantt1, Ashok Cattamanchi2, Elizabeth Krantz3, Amalia Magaret4, Stacy Selke5, Steven R Kuntz5, Meei-Li Huang5, Lawrence Corey6, Anna Wald7, Corey Casper8. 1. Department of Pediatrics, University of Washington, USA; Seattle Children's Hospital, Seattle, WA, USA; Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Electronic address: sgantt@cfri.ca. 2. Department of Medicine, University of Washington, USA. 3. Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 4. Department of Laboratory Medicine, University of Washington, USA; Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 5. Department of Laboratory Medicine, University of Washington, USA. 6. Department of Medicine, University of Washington, USA; Department of Laboratory Medicine, University of Washington, USA; Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Clinical Research Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 7. Department of Medicine, University of Washington, USA; Department of Laboratory Medicine, University of Washington, USA; Department of Epidemiology, University of Washington, USA; Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 8. Department of Medicine, University of Washington, USA; Department of Laboratory Medicine, University of Washington, USA; Department of Epidemiology, University of Washington, USA; Department of Global Health, University of Washington, USA; Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Clinical Research Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Abstract
BACKGROUND: Human herpesvirus 8 (HHV-8) replication increases the risk of Kaposi sarcoma (KS). Highly-active antiretroviral therapy (HAART) reduces the incidence of KS, and regimens that contain protease inhibitors (PIs) may be particularly effective. OBJECTIVE: To determine whether PI-based HAART regimens may more effectively inhibit HHV-8 shedding compared to regimens without PIs. STUDY DESIGN: Prospective, observational study of 142 HIV-1 and HHV-8 co-infected men conducted in Seattle, Washington. Quantitative HHV-8 PCR testing was performed on daily swabs of the oropharynx, the primary site of HHV-8 replication. Associations between antiretroviral regimen and detection of HHV-8 DNA in swabs were evaluated using generalized estimating equations. RESULTS: HHV-8 DNA was detected in 3016 (26%) of 11,608 specimens collected. PI-based HAART was associated with a statistically significantly lower frequency of detection (RR 0.2; 95% CI 0.1-0.5) compared to ART-naïve persons, whereas HAART without a PI was not (RR 0.7; 95% CI 0.4-1.3). Compared to ART-naïve persons, there was also a trend toward lower quantities of HHV-8 detected during treatment with HAART regimens that contained a PI. These associations between PIs and measures of HHV-8 shedding could not be attributed to use of nelfinavir, which inhibits HHV-8 replication in vitro, and were independent of CD4 count and HIV plasma viral load (VL). CONCLUSIONS: HAART regimens that contain PIs appear to decrease HHV-8 shedding compared to NNRTIs. Further study of PI-based HAART is warranted to determine the optimal regimens for prevention and treatment of KS.
BACKGROUND:Human herpesvirus 8 (HHV-8) replication increases the risk of Kaposi sarcoma (KS). Highly-active antiretroviral therapy (HAART) reduces the incidence of KS, and regimens that contain protease inhibitors (PIs) may be particularly effective. OBJECTIVE: To determine whether PI-based HAART regimens may more effectively inhibit HHV-8 shedding compared to regimens without PIs. STUDY DESIGN: Prospective, observational study of 142 HIV-1 and HHV-8 co-infected men conducted in Seattle, Washington. Quantitative HHV-8 PCR testing was performed on daily swabs of the oropharynx, the primary site of HHV-8 replication. Associations between antiretroviral regimen and detection of HHV-8 DNA in swabs were evaluated using generalized estimating equations. RESULTS:HHV-8 DNA was detected in 3016 (26%) of 11,608 specimens collected. PI-based HAART was associated with a statistically significantly lower frequency of detection (RR 0.2; 95% CI 0.1-0.5) compared to ART-naïve persons, whereas HAART without a PI was not (RR 0.7; 95% CI 0.4-1.3). Compared to ART-naïve persons, there was also a trend toward lower quantities of HHV-8 detected during treatment with HAART regimens that contained a PI. These associations between PIs and measures of HHV-8 shedding could not be attributed to use of nelfinavir, which inhibits HHV-8 replication in vitro, and were independent of CD4 count and HIV plasma viral load (VL). CONCLUSIONS: HAART regimens that contain PIs appear to decrease HHV-8 shedding compared to NNRTIs. Further study of PI-based HAART is warranted to determine the optimal regimens for prevention and treatment of KS.
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