Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia with Anal Cancer Risk in Persons Living with HIV in the United States and Canada

Background: People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. Methods: We studied 102 777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. Results: Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/μL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/μL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6). Conclusions: Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk

Late cardiac effects after treatment for childhood Hodgkin's disease with chemotherapy and low-dose radiotherapy.

Twenty-four patients under 18 years when treated for Hodgkin's disease (20 male, four female) were examined no less than five years after the completion of the treatment. The mean age was 17 years (range 9.5-25.0 years) at the time of study. All patients received six courses of cyclophosphamide-oncovin-procarbazine-prednisolone chemotherapy; in addition, nine patients received low-dose radiotherapy excluding the mediastinum and eight of 24 patients received mediastinal radiotherapy; the dose was between 20-30 Gy. All patients had normal cardiovascular findings on clinical examination. ECG and chest radiography were within normal limits in all patients. Resting left ventricular ejection fraction and fractional shortening were decreased in only one patient (4%), but there was no significant difference between the patient group and a control group for left ventricular systolic function (p > 0.05). In the patient group, early diastolic peak velocity, peak velocity at atrial contraction, left ventricular isovolumic relaxation time, and the rate of decrease of flow velocity in early diastole were significantly different from that of the control group (p < 0.05). In conclusion, the late effects of our treatment protocol for Hodgkin's disease appear to be minimal. These observations support combined modality, low-dose irradiation regimens in children and adolescents and suggest the need for careful cardiac screening of treated patients