HIV-Related Cancers: Waiting (and Waiting) for the Storm

     David Alain Wohl, MD - Clinical Assistant Professor, The University of North Carolina

There has been considerable concern that as persons with HIV infection live longer, thanks to HAART, they would be vulnerable to a variety of cancers. Fortunately, however, a clear trend toward increased malignancies has yet to materialize. Most HIV-associated cancers have actually declined since the advent of HAART - although an exception may be non-Hodgkin's lymphoma which seems to be occurring at a similar rate as in the pre-HAART era. There were no oral presentations related to malignancies but a variety of posters described the epidemiology, of HIV-related malignancies and the impact of HAART on incidence and survival.

Infections Fade, Leaving Some Cancers Standing
A study of the causes of death among patients followed in the French Aquitaine Cohort reveals the role malignancies continue to play in the era of HAART (Abstract 299). Among the 2,200 patients followed in this study there were 107 deaths from 1998 to 1999. While bacterial infections represented the greatest proportion of causes of death (21%), malignancies when aggregated accounted for 38% of the reported mortalities. Non-Hodgkin's lymphoma occurred in 14 patients, Kaposi's sarcoma in 8 and Hodgkin's lymphoma in 3. In addition, there were 16 non-AIDS defining cancers such as carcinoma of the lung in 7, hepatocellular carcinoma in 2, parotid cancer in 1 and anal cancer in 1. Some have suggested that there has been an increase in non-AIDS-associated cancers in recent years but this has not been well documented. The AIDS Clinical Trials Group is developing a retrospective review of malignancies across studies and eras to examine changes in the incidence, prevalence and types of cancers diagnosed among participants.

HAART Improves CNS Lymphoma and KS Survival
In a study of the effects of HAART on survival of primary central nervous system lymphoma (PCNSL), investigators from Germany observed the clinical courses of 29 patients with biopsy proven PCNSL (Abstract 590). Six of the patients were being treated with HAART and 23 were not. Slightly less than half of the patients received radiation to treat the lymphoma. In a multivariate analysis, the combination of HAART and radiation was found to be associated with a 6 fold greater chance of survival. Patients treated with both these therapies lived a median of 1093 days compared to 132 days in those only treated with radiation and 33 days for patients who did not receive radiation or HAART. One patient who responded to HAART with an increase in his CD4 cell count to above 700/cu mm is still alive 5 years after the diagnosis of PCNSL and his brain lesion has disappeared.

As in the above paper regarding lymphoma, HAART improves the outcome of KS and certainly there is no doubt KS rates have declined with the advent of HAART. To assess whether HAART reduces levels of HHV-8, the causative agent of KS, investigators in London studied 21 men with KS before and after initiation of HAART (Abstract 588). Blood levels of HHV-8 were measured in these patients and 15 control subjects without KS but also commencing HAART. Of the subjects with KS, 71% had antibodies to HHV-8 in their blood and 76% had detectable plasma HHV-8 by PCR prior to initiating HAART. The median baseline CD4 cell count and HIV viral load were 81 cells/mm3and 292,634 copies/ml, respectively. In contrast, 53% of subjects without KS were HHV-8 seropositive and 33% were PCR positive. In this group the median baseline CD4 cell count and HIV viral load were 135 cells/mm3and 115,439 copies/ml, respectively. Subjects were followed up for a median of 36 weeks during which 10 of the patients with KS demonstrated either partial or complete resolution of KS with HAART alone, 7 required additional chemotherapy, 3 subjects had progression of their KS but have not received additional KS therapy and 1 subject died of pulmonary KS. Of the KS subjects with plasma HHV-8 detectable by PCR, there was a 1.29 log10 drop in HHV-8 viral load between baseline and 30 weeks of treatment with HAART. Subjects without KS who had detectable plasma HHV-8 were found to have a 2 log10 drop in the HHV-8 viral load between baseline and 30 weeks of HAART. Therefore, almost half the subjects with AIDS-KS demonstrated a clinical response to HAART alone. If only the stuff were easier to take.

In summary, there were little data regarding the treatment of AIDS-related malignancies presented in Chicago this year. A venue where much more information will be available will be the National Cancer Institute sponsored Fifth International AIDS Malignancy Conference in Bethesda, Maryland April 23-25. Register at: http://ctep.info.nih.gov/AIDSOncoResources/5thAidsConf.htm.