Reduced human herpesvirus-8 oropharyngeal shedding associated with protease inhibitor-based antiretroviral therapy

doi:10.1016/j.jcv.2014.03.002

Observational Study

. 2014 Jun;60(2):127-32.

doi: 10.1016/j.jcv.2014.03.002. Epub 2014 Mar 13.

Reduced human herpesvirus-8 oropharyngeal shedding associated with protease inhibitor-based antiretroviral therapy

Affiliations

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.

PMID: 24698158
PMCID: PMC4020979
DOI: 10.1016/j.jcv.2014.03.002

Observational Study

Reduced human herpesvirus-8 oropharyngeal shedding associated with protease inhibitor-based antiretroviral therapy

Soren Gantt et al. J Clin Virol. 2014 Jun.

. 2014 Jun;60(2):127-32.

doi: 10.1016/j.jcv.2014.03.002. Epub 2014 Mar 13.

Authors

Affiliations

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.

PMID: 24698158
PMCID: PMC4020979
DOI: 10.1016/j.jcv.2014.03.002

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.

Keywords: Antiretroviral therapy; Human herpesvirus 8; Kaposi sarcoma; Protease inhibitor.

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Conflict of interest statement

Competing Interests: None declared.

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References

1. Eltom MA, Jemal A, Mbulaiteye SM, Devesa SS, Biggar RJ. Trends in Kaposi's sarcoma and non-Hodgkin's lymphoma incidence in the United States from 1973 through 1998. J Natl Cancer Inst. 2002;94:1204–10. - PubMed
1. Maurer T, Ponte M, Leslie K. HIV-associated Kaposi's sarcoma with a high CD4 count and a low viral load. N Engl J Med. 2007;357:1352–3. - PubMed
1. Krown SE, Lee JY, Dittmer DP. More on HIV-associated Kaposi's sarcoma. N Engl J Med. 2008;358:535–6. author reply 36. - PMC - PubMed
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1. Dupont C, Vasseur E, Beauchet A, Aegerter P, Berthe H, de Truchis P, et al. Long-term efficacy on Kaposi's sarcoma of highly active antiretroviral therapy in a cohort of HIV-positive patients. CISIH 92. Centre d'information et de soins de l'immunodeficience humaine. Aids. 2000;14:987–93. - PubMed

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[1] Eltom MA, Jemal A, Mbulaiteye SM, Devesa SS, Biggar RJ. Trends in Kaposi's sarcoma and non-Hodgkin's lymphoma incidence in the United States from 1973 through 1998. J Natl Cancer Inst. 2002;94:1204–10. - PubMed

[2] Eltom MA, Jemal A, Mbulaiteye SM, Devesa SS, Biggar RJ. Trends in Kaposi's sarcoma and non-Hodgkin's lymphoma incidence in the United States from 1973 through 1998. J Natl Cancer Inst. 2002;94:1204–10. - PubMed

[3] Maurer T, Ponte M, Leslie K. HIV-associated Kaposi's sarcoma with a high CD4 count and a low viral load. N Engl J Med. 2007;357:1352–3. - PubMed

[4] Maurer T, Ponte M, Leslie K. HIV-associated Kaposi's sarcoma with a high CD4 count and a low viral load. N Engl J Med. 2007;357:1352–3. - PubMed

[5] Krown SE, Lee JY, Dittmer DP. More on HIV-associated Kaposi's sarcoma. N Engl J Med. 2008;358:535–6. author reply 36. - PMC - PubMed

[6] Krown SE, Lee JY, Dittmer DP. More on HIV-associated Kaposi's sarcoma. N Engl J Med. 2008;358:535–6. author reply 36. - PMC - PubMed

[7] Casper C. The increasing burden of HIV-associated malignancies in resource-limited regions. Annu Rev Med. 2011;62:157–70. - PubMed

[8] Casper C. The increasing burden of HIV-associated malignancies in resource-limited regions. Annu Rev Med. 2011;62:157–70. - PubMed

[9] Dupont C, Vasseur E, Beauchet A, Aegerter P, Berthe H, de Truchis P, et al. Long-term efficacy on Kaposi's sarcoma of highly active antiretroviral therapy in a cohort of HIV-positive patients. CISIH 92. Centre d'information et de soins de l'immunodeficience humaine. Aids. 2000;14:987–93. - PubMed

[10] Dupont C, Vasseur E, Beauchet A, Aegerter P, Berthe H, de Truchis P, et al. Long-term efficacy on Kaposi's sarcoma of highly active antiretroviral therapy in a cohort of HIV-positive patients. CISIH 92. Centre d'information et de soins de l'immunodeficience humaine. Aids. 2000;14:987–93. - PubMed

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Reduced human herpesvirus-8 oropharyngeal shedding associated with protease inhibitor-based antiretroviral therapy

Affiliations

Reduced human herpesvirus-8 oropharyngeal shedding associated with protease inhibitor-based antiretroviral therapy

Authors

Affiliations

Abstract

Conflict of interest statement

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