With the increased survival of HIV-infected patients, cancer and other non-AIDS complications are becoming increasingly important causes of morbidity.  Crum-Cianflone et al. analyzed data from their prospective Natural History Study and showed that the rates of anal cancer continue to increase in the HAART era.  Indeed, Among 5,029 HIV-infected persons with 39,291 PYs of follow-up, anal cancer rates increased 5-fold from the pre-HAART (17 per 100,000 PYs) to HAART (91 per 100,000 PYs) era, p=0.007. Rates continued to increase during the HAART era, reaching 244 per 100,000 PYs in 2006-2008.

Patients with cancer diagnosis were not significantly immunosuppressed; their median CD4 count (375 cells/mm³) was not significantly lower than non-cancer patients.

Concordant with this observation, Berman et al. presented a pilot study showing a high rate of infection with cancer-inducing HPV strains and abnormal anal cytology in a cohort of 62 HIV+ males receiving the HPV vaccine.  Seropositivity to HPV-16 and 18 were 40.3% and 9.7%, respectively.  Ten of the 25 HPV-16 seropositive patients had detectable HPV DNA.  Twelve patients (all MSM) had abnormal anal PAPs (6 ASCUS, 6 LSIL). Seropositivity, HPV DNA results, and PAPs were all independent of CD4 count, CD4%, and HIV-1 VL.

Another troubling note was a presentation by Batra et al., that excisional therapy for cervical intraepithelial neoplasia (CIN) was more likely to fail among HIV-positive women (45.0% had persistent low-grade CIN or higher-grade PAP at 4 months, vs. 16.8% of HIV-negative women.  These poor outcomes were not improved among those receiving HAART.

The pathogenic mechanisms of all non-AIDS-defining malignancies (NADM) are still incompletely understood.  Kesselring et al. showed that both duration of immunodeficiency and persistent viremia on HAART were independent predictors of NADM.  Cancers identified in the cohort were very diverse, including anal, lung, hematological, Hodgkin’s lymphoma and cancers of the digestive tract.  Median CD4 count at cancer diagnosis was high (358 cells/mm³; IQR 210-550).  In multivariate models, cumulative exposure to CD4 count < 350 cells/mm³, but not current CD4 count predicted NADM: HR 1.09 (1.03-1.17, p=0.005) for each additional year of exposure. Longer exposure to detectable viremia was also associated with an increased risk of NADM, HR 1.09 (1.01-1.17, p=0.02) for each additional year.

Breaking with the cancer focus of this session – and with the negative connotation of the previous observations – Casado presented evidence of a possible improvement of hepatic fibrosis, demonstrated by elastometry, in HIV/HCV co-infected patients following HCV therapy.  In a prospective cohort of 294 patients followed for >1 year after Peg-IFN + RBV therapy (43% of which achieved SVR), fibrosis improvement by elastometry was observed in 35% of patients.  Improvement was more common in patients achieving SVR (44% vs 23%; p=0.03). After multivariate analysis, SVR (0.76) and therapy duration (0.88 per month) were associated with fibrosis regression, although SVR was not statistically significant (p=0.08) after adjusting by histological cirrhosis.