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


METHODS
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.
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.
Soren
S
Gantt
Department of Medicine, University of Washington, USA.
Ashok
A
Cattamanchi
Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Elizabeth
E
Krantz
Department of Laboratory Medicine, University of Washington, USA; Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Amalia
A
Magaret
Department of Laboratory Medicine, University of Washington, USA.
Stacy
S
Selke
Department of Laboratory Medicine, University of Washington, USA.
Steven R
SR
Kuntz
Department of Laboratory Medicine, University of Washington, USA.
Meei-Li
ML
Huang
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.
Lawrence
L
Corey
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.
Anna
A
Wald
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.
Corey
C
Casper
D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006566:Herpesviridae Infections / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009305:Nasopharynx / Q000821:virology*; D011446:Prospective Studies; D019562:Viral Load; D017201:Virus Shedding; D014861:Washington; D055815:Young Adult
D004279:DNA, Viral; D017320:HIV Protease Inhibitors
Antiretroviral therapy; Human herpesvirus 8; Kaposi sarcoma; Protease inhibitor