The advent of effective antiretroviral therapy has served to decrease rates of AIDS-defining malignancies such as Kaposi sarcoma and non-Hodgkin lymphoma.107 These vascular and lymphoid malignancies have well-described pulmonary manifestations.108 In contrast, as people with HIV are living longer due to the impact of HAART, rates of non–AIDS-defining malignancies are climbing.8,109,110 An analysis of an HIV-positive cohort in England found rates of 6.7 per 10,000 person-years after HAART, compared to 0.8 per 10,000 person-years before HAART. Compared to the general population, the relative risk (RR) was 8.93 (95% CI, 4.92 to 19.98).8 Similarly, a cohort study109 in France found that rates of lung cancer were twofold higher in the post-HAART era, with higher increased risk in injection drug users (standardized incident ratio, 4.70; 95% CI, 2.83 to 7.34) and in women (standardized incident ratio, 6.59; 95 CI, 3.4 to 11.5). This increased risk in women was believed to be in keeping with trends in the general French population.109 In addition, confounders such as smoking have made interpretation of these data difficult. Data from a large cohort111 of injection drug users in the United States showed that rates of lung cancer deaths had increased in the post-HAART era (mortality rate ratio, 4.7; 95% CI, 1.7 to 16), and that after adjustment for smoking (which was comprehensively recorded within the cohort), HIV was associated with increased lung cancer risk (hazard ratio, 3.6; 95% CI, 1.6 to 7.9). Postulated mechanisms include possible direct oncogenic effects of HIV, genetic instability due to HIV integration leading to increased susceptibility for carcinogens such as tobacco, or possible decreased immune surveillance for malignant cells.110,111 Prognosis appears to be worse than in the general population, and further work evaluating treatment in the setting of HIV may be required.