Anti-HIV medications can completely suppress Kaposi’s sarcoma-associated herpes virus (KSHV) (the virus that causes KS, one of the AIDS-defining cancers) but take at least twelve months to do so, providing an explanation for the remarkable decline in KS seen in resource-rich nations in the post-HAART era, according to an article published in the March 5th issue of AIDS.
KS remains a major AIDS-defining illness in resource-limited nations, especially in Africa, where the availability of HAART is still limited.
Researchers at University College, London recruited 27 gay men attending a central London HIV outpatient clinic who were about to start their first HAART regime. Prior to starting HAART, four of the men had symptomatic KS (lesions on their skin), and 20 (74%) had detectable latent nuclear antigen (LANA) antibodies. This is the standard antibody test used in the clinic for KSHV.
A second antibody test (an adapted K8.1 ELISA test for the detection of anti-KSHV lytic (destructive) antibodies) was also used in the this study, and only 12 (44%) had detectable anti-lytic antibodies. Three of the four men with symptomatic KS were positive in one or both of the antibody tests.
Baseline KSHV viral load was determined in both plasma and peripheral blood mononuclear cells (PBMC). Only seven (26%) had detectable KSHV DNA in plasma, whereas 14 (52%) showed detectable KSHV DNA in PBMC. The men with symptomatic KS had lower mean viral loads in both plasma (948 vs. 6686 copies/ml) and PBMC (17 vs. 57 copies/ml), respectively, although, given that only four men had KS symptoms, this did not become a statistically significant finding.
After a median of 23 months follow-up on HAART there were no significant changes or trends in anti-LANA antibodies in any of the men. However, the percentage of men who acquired anti-lytic antibodies increased over time, suggesting that it takes twelve months of HAART to achieve this kind of immunity. After one year, however, these antibodies began to decline. This appeared to be a response to the significant reduction in KSHV viral load seen in PBMCs after twelve months (Odds Ratio: 0.40; 95% CI, 0.26 - 0.63; no P value reported). KSHV viral load in plasma also declined significantly within 12 months, with only 12.5% detectable after a year, compared with 26% at baseline. After two years, no one had detectable KSHV in plasma.
Three of the four men with symptomatic KS had complete remission of their KS lesions on HAART, and the fourth had stable disease. All four responded to HAART with HIV- and KSHV-specific immune reconstitution. In particular there was a significant increase of KSHV-specific CD8 T cell responses during the first six to nine months on HAART in three of the four men, which persisted throughout the study. KSHV viral load became undetectable in plasma after a year in three of the men, and after 23 months in the fourth. However, KSHV viral load remained detectable in PBMC in all four men throughout the study period.
Eight men in the study were followed for a further 15 months, and at this point (more than three years after starting HAART), only one man had detectable KSHV viral load in PBMC. This, say the authors, shows that HAART can suppress KSHV for a long time, although it does appear to take several years to achieve full suppression.
The authors conclude that “HAART promotes long-term KSHV immune reconstitution in patients with and without KS… however, prolonged HAART (more than 12 months) is necessary for these anti-KSHV effects to be established and maintained.”
Further information on this website
In men with HIV, risk of developing new KS lesions predicted by HHV-8 factors, not CD4 count or VL - news story
HAART improves survival in men with KS and non-Hodgkin lymphoma - news story
Kaposi's Sarcoma - fact sheet
Bourboulia D et al. Short- and long-term effects of highly active antiretroviral therapy on Kaposi sarcoma-associated herpes virus immune responses and viraemia. AIDS 18; 485-493, 2004.