Of 5,850 subjects included in the analysis, 4,480 (76.6%) were diagnosed with AIDS during the pre-HAART era (1980–1995), and 1,370 (23.6%) were diagnosed during the HAART era (1996–2007). The proportion of male subjects declined across the calendar periods from 52.6% to 49.1%. By race/ethnicity, most subjects were non-Hispanic black during both time periods (60.1% and 66.7%, respectively). The proportion of subjects 0–4 years old at AIDS onset declined from 73.3% during 1980–1995 to 48.3% during 1996–2007. This reflects declines in perinatal HIV transmission over time and the effectiveness of HAART in delaying AIDS onset to older ages.
During the pre-AIDS period (60 to 7 months prior to AIDS diagnosis), there were 2 cases of lymphocytic leukemia, 1 ganglioneuroblastoma, and 1 poorly-specified cancer. There were 44 cancers observed during the AIDS onset period (6 months prior to AIDS to 3 months after AIDS). Most malignancies observed during this period were NHLs (n=35, 80%).
shows the distribution of person-time at-risk for cancer after AIDS diagnosis, by attained year and age-groups. The proportion of person-time contributed by subjects aged 0–4 years declined from 100% in 1981 to 52% in 1991. Subsequently, person-time contributed by people aged 5–9 years increased from 35% in 1991 to 42% in 2001. During 2007 more than half of the person-time was contributed by people with a current age of 10–24 years, but only 10% of person-time was among subjects aged 20 years or older.
Distribution of person-years for cancer risk by attained age-group and year among people diagnosed with AIDS during childhood
A total of 106 cancer cases were observed during the 10 years after AIDS onset (). Relative to the general population, overall cancer risk was strongly elevated during both the pre-HAART (SIR 40; 95%CI, 31–51) and HAART eras (SIR 17; 95%CI, 12–23). AIDS-defining cancers were the most common cancer type during both the pre-HAART (84%) and HAART periods (70%). Risks were significantly elevated during both periods for KS (SIRs 1694; 95%CI, 986–2712 and 1146; 95%CI, 236–3349, respectively). Of the 20 KS cases, the median age at cancer diagnosis increased from 2 years in the pre-HAART era to 10 years in the HAART era.
Cancer risk among people diagnosed with AIDS during childhood relative to the general population
In the 10 years after AIDS onset, NHL was the most common cancer overall (60%) and the most common AIDS-defining cancer (76%). Risk of NHL was elevated during both time periods (SIRs 338; 95%CI, 242–458 and 116; 95%CI, 74–175, respectively). By subtype, risk of CNS lymphoma was especially elevated during the pre-HAART (SIR 1994; 95%CI, 647–4656) and HAART eras (SIR 1088; 95%CI, 354–2541, ). Similar to KS, the median age at NHL onset increased from 3 years during the pre-HAART era to 12 years in the HAART era. No cases of cervical cancer were observed.
There were 19 non-AIDS-defining cancers diagnosed during the study, corresponding to elevated risks during both the pre-HAART (SIR 5; 95%CI, 2–10) and HAART eras (SIR 6; 95%CI, 3–10, ). The most common was leiomyosarcoma (n=9), followed by other soft tissue cancers (n=3), poorly specified cancers (n=3) and lymphocytic leukemia (n=2). Risk of leiomyosarcoma was markedly elevated during both time periods (4 cases in the pre-HAART era, median age 5 years, SIR 863; 95% CI, 235–2211; 5 cases in the HAART era, median age 5 years, SIR 533; 95%CI, 173–1243). There was an elevated risk for soft tissue cancers (other than leimyosarcoma) observed in the pre-HAART era (SIR 21; 95%CI, 3–77). The 2 observed cases were a rhabdomyosarcoma (in a 6 year-old) and a neurofibrosarcoma (in a 3 year-old). The 1 soft tissue cancer in the HAART era (neuroblastoma, age 9 years at cancer diagnosis) did not manifest as a significantly elevated risk relative to the general population.
Other non-AIDS-defining cancers represented single occurrences but contributed to the elevated overall risk. The case of Hodgkin lymphoma was of the nodular sclerosis subtype and occurred in a 16 year-old. The lung cancer was a spindle cell sarcoma in a 4 year-old.
Cancer incidence rates are presented in . Overall incidence declined 62% relative to widespread HAART use (RR 0.38; 95%CI, 0.23–0.64). This decrease was related to steep declines in the incidence of KS (138 per 100,000 person-years during the pre-HAART era vs. 17 per 100,000 person-years during the HAART era; RR 0.13; 95%CI, 0.02–0.74) and NHL (332 vs. 132 per 100,000 person-years; RR 0.40; 95%CI, 0.21–0.75). There was no apparent decline in the incidence of diffuse large B cell (DLBCL) NHL, although incidence of unspecified NHL declined 82% (RR 0.18; 95%CI, 0.06–0.49). Incidence of Burkitt NHL and CNS NHL declined; however, these decreases were not significant.
Cancer incidence among people diagnosed with AIDS during childhood, by current calendar year period
Overall, the incidence of non-AIDS-defining cancers did not change (65 per 100,000 person-years in the pre-HAART era vs. 63 per 100,000 person-years in the HAART era; RR 0.98; 95%CI, 0.33–2.86). There was a non-significant decline in the incidence of soft tissue cancers other than leiomyosarcoma but no change in the incidence of leiomyosarcoma ().