June 11, 2002
To examine the effect of highly active antiretroviral therapy (HAART) on incidence of initial AIDS-defining illnesses (ADIs) and survival after individual ADIs, researchers compared two periods of AIDS diagnoses reported to the National AIDS Registry in Australia: pre-HAART (1993-1995) and HAART (1996-2000). Analyses were based on all initial ADIs.
AIDS cases in which HIV diagnosis was within three months of AIDS diagnosis were designated "late" HIV diagnoses (LDACs), whereas cases where HIV diagnosis was more than three months before AIDS were considered "early" HIV diagnoses (EDACs). Despite an overall decline in AIDS cases, from 949 in 1994 to 217 by 2000, the number of LDACs was relatively stable during 1993-2000, resulting in an increasing proportion of LDACs from 15.7 percent in 1993 to 1995, to 30.1 percent in 1996 to 2000. Because some patients had more than one ADI at diagnosis, total ADIs (n=5,017) were higher than AIDS cases, but these also peaked in 1994 (n=1,080), and declined to 267 in 2000. There were 2,597 AIDS cases diagnosed during 1993-1995 (pre-HAART) and 1,754 cases diagnosed during 1996-2000 (HAART).
Although notification rates of all ADIs except tuberculosis (TB) declined from 1993-1995 to 1996-2000, the proportion increased for Pneumocystis carinii pneumonia (PCP)(25.9 to 30.4 percent), AIDS dementia complex (ADC)(5.2 to 6.8 percent), non-Hodgkin's lymphoma (NHL)(4.4 to 6.3 percent), and TB (.5 to 2.7 percent). In contrast, the proportion decreased for Mycobacterium avium complex (MAC)(9.6 to 7.7 percent), cytomegalovirus disease (CMV)(6.6 to 4.2 percent), and cryptosporidiosis (3.9 to 2.3 percent).
Among LDACs, there was an increase in proportion of HIV wasting syndrome (7.8-15 percent) and TB (.2-4 percent), but no significant change in proportion of all other ADIs. Among EDACs, following introduction of HAART, the proportion increased for ADC (5.3-7.8 percent), NHL (4.6-7.6 percent), and TB (.5-2.1 percent) but decreased for CMV disease (7.2-4.5 percent) and cryptosporidiosis (4.2-2.5 percent).
Total LDACs (1993-2000) had a considerably higher proportion of PCP (47.2 percent vs. 22.4 percent) and a higher proportion of toxoplasmosis (5.3 percent vs. 3.6 percent) and TB (2.4 percent vs. 1.1 percent). In contrast, LDACs had a lower proportion of KS (10.2 percent vs. 13.6 percent), MAC infection (5 percent vs. 10.1 percent), CMV disease (3.4 percent vs. 6.2 percent), NHL (3.7 percent vs. 5.6 percent), ADC (4.4 percent vs. 6.2 percent) and cryptosporidiosis (2 percent vs. 3.6 percent). The proportion of other ADIs were similar between EDACs and LDACs.
Survival analyses were based on 98 percent (4,262) of the population who had follow up after AIDS diagnosis. Median survival following AIDS increased from 19.6 months after AIDS cases diagnosed during 1993-1995 to 39.6 months for AIDS cases diagnosed during 1996-2000. Median survival increased more than fourfold for ADC (11.9-48.2 months), twofold to threefold for PCP (23.6-49.1 months), esophageal candidiasis (22.7-46.1 months), KS (21.1-46.8 months), HIV wasting syndrome (17.8-42.5 months), toxoplasmosis (12.2-34.7 months), MAC infection (12.7-29.2 months), and CMV disease (11.3-32.1 months). In contrast, median survival was stable for NHL (7.5-8.8 months), and there were nonsignificant increases for cryptococcosis (13.5-20 months), and chronic herpes simplex infection (25.3-37.7 months).
Researchers confirmed the impact of HAART on the natural history of AIDS-related opportunistic disease at a population level in Australia. The impact is most visible in the striking improvements in survival following almost all AIDS-related illnesses. Based on cases of EDACs in 1996-2000, with probable earlier exposure to more potent antiretroviral therapy, there does appear to be a differential impact of HAART on prevention of individual ADIs, with relatively poorer efficacy against NHL and ADC and relatively greater efficacy against CMV disease and cryptosporidiosis. The continued impact of this therapy despite development of AIDS-related illnesses at advanced immune deficiency was particularly encouraging to researchers.
Journal of Acquired Immune Deficiency Syndromes
05.01.02; Vol. 29; No. 4: P. 388-395; Gregory J. Dore; Yueming Li; Ann McDonald; Hugo Ree; John M. Kaldo