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Background:  Antiretroviral therapy (ART) has been associated with a dramatic decline in Kaposi’s sarcoma (KS) among persons with HIV. This effect may due to immune reconstitution, anti-angiogenic factors or a direct antiviral effect on Human Herpesvirus 8 (HHV-8). We conducted a prospective, observational study to determine the effect of specific ART on HHV-8 oropharyngeal shedding.

Methods:   HIV- and HHV-8-infected persons collected daily samples for the quantification of HHV-8 DNA from the oropharynx. Use of specific ART on each day was recorded. HHV-8 DNA was quantified using real-time PCR, and HHV-8 shedding rates were described.

Results:  In all, 54 participants collected 6007 days of samples. The median CD4 count was 335 (1 to 1122), and HIV plasma RNA was 6388 (7 to 376,057) at enrollment. In persons not on ART, HHV-8 was detected on 34% of 2319 days. Comparing days with regimens containing each specific drug, HHV-8 shedding was lowest on days with tenofovir (HHV-8 detected 0% of 123 days with tenofovir vs. 29% of 6012 days without), amprenavir (0% of 306 vs 30% of 5829), indinavir (0% of 339 vs. 30% of 5796), lopinavir/ritonavir (0% of 295 vs 30% of 5840), and efavirenz (0% of 613 vs. 32% of 5522). Other protease inhibitors (PI) (regimens with nelfinavir 16% vs 31% without, saquinavir 15% vs 30%), and nucleoside reverse transcriptase inhibitors (NRTI) (abacavir 10% vs 31%, didanosine 18% vs 30%, lamivudine 16% vs 38%, and zidovudine 26% vs 29%) were associated with smaller differences in shedding rates. Stavudine, zalcitabine, or nevirapine use was not associated with lower HHV-8 shedding rates. Shedding rates were lower on days when any PI (11% with PI vs 40% without), NRTI (25% vs. 34%), or non-nucleoside reverse transcriptase inhibitors (NNRTI) (23% vs 30%) were used. Regimens with at least 1 drug in each class were associated with the lowest HHV-8 shedding rates (0% of 393 days), followed by the combination of NRTI and PI (13% of 1956), NRTI and NNRTI (35% of 791), and NRTI only (65% of 676). Conclusions:  The use of certain antiretroviral agents is associated with low rates of HHV-8 oropharyngeal shedding. No HHV-8 shedding was observed with the use of amprenavir, efavirenz, indinavir, lopinavir/ritonavir, or tenofovir. The choice of ART regimen and the timing of initiation may effect HHV-8 replication, transmission and development of KS.

Keywords: HHV-8; Kaposi's Sarcoma; Antiretroviral Therapy