Background: People with AIDS (PWA) have elevated risk for Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), and cervical cancer. Since 1996, HAART has provided opportunity for immune reconstitution in PWA. Population-based data on long-term and recent trends in risk for AIDS-associated cancers are limited.

Methods: We linked AIDS and cancer registries in 11 US regions to study cancer risk in 375,933 PWA (1980-2002). Standardized incidence ratios (SIRs) compared cancer risk in PWA for the 2 years after AIDS onset with risk in the general population. SIRs were calculated for AIDS onset in 3 periods: 1980-89, 1990-95, and 1996-02 (HAART era). We evaluated trends over calendar time using Poisson regression.

Results: KS risk fell over time but remained substantially elevated in the HAART era (n=7,864; SIRs 52,900, 22,050, 3,642, in 1980-89, 1990-95, and 1996-02). Specifically, KS risk declined during 1990-95 (relative risk [RR] 0.78, 95%CI 0.75-0.82, per yr), continuing a decline that began in the 1980s. Risk dropped further in 1996 (RR 0.41, 0.28-0.60) but subsequently remained flat (RR 0.96, 0.81-1.13, per yr). The same pattern was seen for NHL (n=4,527; SIRs 79.8, 53.2, 22.6 for the 3 periods). Risk declined in the 1980s and during 1990-95 (RR 0.88, 0.84-0.92, per yr), fell further in 1996 (RR 0.64, 0.48-0.85), and remained flat within the HAART era (RR 1.02, 0.91-1.14 per yr). For central nervous system (CNS) NHL (n=1,247), the trend was similar, but SIRs were much higher (4,997, 4,847, 1,015 for the 3 periods) and the drop in 1996 was larger (RR 0.36, 0.23-0.58). Finally, cervical cancer risk was lower overall (n=74; SIRs 7.7, 4.2, 5.3 across the 3 periods) and did not change over time (RR 1.04, 95%CI 0.94-1.15, per yr during 1990-2002).

Conclusions: Among PWA in the US, declines over time in KS and NHL are likely due to improvements in HIV therapy. Risk began declining in the 1980s, continued to fall in 1990-95, and dropped dramatically in 1996, reflecting prompt uptake of HAART. HAART had greatest effect in reducing CNS NHL, followed by KS. Cervical cancer risk did not change over time, suggesting that immunity is less relevant for this malignancy. In the HAART era, PWA remained at substantially elevated risk for KS and NHL, which may be because of persisting difficulties in accessing care or frequent HIV drug resistance. These findings point to a need for more effective therapies targeted to the most immunosuppressed segments of the HIV population.