Treatment with antiretroviral drugs dramatically enhances the response of the immune system to Kaposi's sarcoma herpes virus (KSHV), often clearing the virus from HIV-positive gay men, Swiss investigators report in the online edition of AIDS.
“This is the largest investigation into HAART [highly active antiretroviral therapy]-related changes in KSHV antibody response and viremia among MSM [men who have sex with men],” comment the investigators.
“No clear evidence existed of whether the improvements in cellular immunity and control of viral replication induced by HAART would result in a decrease or increase in humoral immune response,” they add; “we observed increases in both lytic and latent Kaposi’s sarcoma herpes virus antibodies.”
Kaposi's sarcoma is an AIDS-defining cancer. It was the most common malignancy seen in patients with HIV, but rates of the cancer fell dramatically after the introduction of potent, combination antiretroviral therapy.
The cancer is caused by human herpes virus-8 (HHV-8). Earlier, small studies have shown that the initiation of antiretroviral therapy is accompanied by a fall in KSHV load, and an improvement in antibody response specific to this virus.
Investigators from the Swiss HIV Cohort wished to better characterise the impact of HIV therapy on both antibody response to KSHV and viral load in HIV-positive gay and other men who have sex with men who were starting treatment with anti-HIV drugs.
The prospective study involved 272 patients, 22 of whom had Kaposi's sarcoma. They all started antiretroviral therapy between 1996 and 2004.
Each patient provided two blood samples: one at the initiation of HIV treatment, the second 24 months later. These were tested for latent and lytic KSHV antibodies as well as KSHV viral load. The investigators then analysed the factors associated with changes in both antibody response and KSHV load.
At the time HIV therapy was initiated, 69% had latent and 75% had lytic antibodies to KSHV. Factors associated with the presence of antibodies included the Kaposi's sarcoma, increasing age, a higher CD8 cell count, and a lower CD4/CD8 ratio.
Overall, 6% of patients had detectable KSHV load on entry to the study. Factors associated with detectable virus were diagnosis with Kaposi sarcoma (p < 0.0001), older age (p = 0.01), and a higher HIV viral load (p = 0.0009).
After 24 months of treatment with anti-HIV drugs, there had been significant improvements in the patients’ immune function, and average HIV viral load fell from almost 400,000 copies/ml to 20,000 copies/ml.
Consistent with these changes in immunity, the number of patients with antibodies to KSHV increased significantly.
The prevalence of latent antibodies increased from 69 to 75% (p = 0.001), whereas the proportion of individuals with lytic antibodies increased modestly from 75 to 78%. There were increases in the proportion of individuals with both antibodies (65 to 70%, p = 0.001), and one antibody (79 to 83%, p = 0.06).
Only one patient still had detectable KSHV after 24 months of HIV therapy (however, seven patients became newly viraemic).
Overall, latent and lytic antibody titres increased by 36%.
Improvements in antibody titres were especially significant in patients with Kaposi's sarcoma, and those with low CD4 cell counts and high HIV load.
Compared to patients without either Kaposi’s sarcoma or detectable KSHV load at baseline, those with the malignancy were significantly more likely to have increased in latent (OR = 22.0; 95% CI, 5.0 to 96.5) and lytic (OR = 5.1; 95% CI, 1.9 to 13.6) antibody titres.
Individuals with an HIV viral load above 100,000 copies/ml at baseline were more than twice as likely to have increases in their lytic antibody titres than those with a baseline HIV viral load below 10,000 copies/ml (OR = 2.4; 95% CI, 1.2 to 9.3).
Titres for both latent and lytic antibodies were more likely to increase for individuals with a pre-HIV treatment CD4 cell count below 50 cells/mm3 than for those with a CD4 cell count above 200 cells/mm3.
“We showed that after 24 months of HAART treatment, the humoral immune response to KSHV increases”, comment the investigators.
They continue, “this was observed in both a large group of MSM without Kaposi sarcoma and in the Kaposi sarcoma cases in whom a parallel loss of detectable KSHV was observed.”
The investigators believe that these improvements in immunity may partly explain “the dramatic protection against Kaposi sarcoma offered by HAART, even when it is initiated at very low CD4 cell counts.”
Sullivan SG et al. Kaposi sarcoma herpes virus antibody response and viremia following highly active antiretroviral therapy in the Swiss HIV Cohort study. AIDS, advance online publication: DOI: 10. 1097/QAD. 0b013e32833b7830, 2010.