Background:  Concern about HAART-related toxicities have led to guidelines that advocate delayed initiation of therapy. Using the HOPS cohort, we analyzed the response to HAART and the incidence of selected toxicities by pre-HAART CD4 cell count (pHCD4) and by time on HAART once initiated.

Methods:  We analyzed a prospective, dynamic cohort of >7800 patients followed since 1993. We stratified patients by pHCD4 (0 to 49, 50 to 199, 200 to 349, 350 to 499, and >500 cells/mm³) and by time on HAART after initiation (took ≥95% of the time vs <95% of the time) and before development of toxicities. We used c² and logistic regression analyses to assess risks for developing three toxicities:  renal insufficiency, peripheral neuropathy, and lipoatrophy in the HAART era.

Results:  Of 2304 patients seen in HOPS clinics at least twice from 1996 to June 30, 2005, there were 124 with renal insufficiency, 278 with peripheral neuropathy, and 168 with lipoatrophy. Approximately 31% of patients received HAART <95% time during follow-up. For each pHCD4R, after 8 years on HAART, CD4 count responses were higher (p <0.001) and the percentage of patients achieving viral loads <50 copies/mL greater (p <0.002) for the ≥95% group vs the <95% group. Incidence of death and of AIDS-defining illnesses decreased with higher pHCD4 (p <0.01) and at each pHCD4 was lower in the ≥95% group vs <95%. Univariate analyses found significantly decreased risk for renal insufficiency, peripheral neuropathy, and lipoatrophy among patients initiating HAART at higher pHCD4 and who remained on HAART ≥95% of the time. In multivariate analyses, independent (p <0.05) risk factors for each outcome were as follows (adjusted odds ratio shown in parentheses): for renal insufficiency, pHCD4 200 to 349 (0.6), 350 to -499 (0.4), >500 (0.3); <95% time on HAART (1.9); hypertension (2.1); African American race (1.6); body mass index <21 (1.9); ART-naïve (2.9); for peripheral neuropathy, pHCD4 200 to 349 (0.7), 350 to 499 (0.6), >500 (0.7); <95% time on HAART (1.5); age >40 years (1.3); stavudine 40 mg twice daily (1.8); any protease inhibitor (PI) (1.3); and for lipoatrophy, pHCD4 200 to 349 (0.5), pHCD4 350+ (0.4), age >40 years (1.8), white race (2.7), stavudine 40 mg twice daily (1.8), didanosine (1.6), tenofovir (0.6), any PI (2.1).

Conclusions:  HOPS patients with higher pre-HAART CD4⁺ cell counts were less likely to develop renal insufficiency, peripheral neuropathy, and lipoatrophy in the HAART era, suggesting the benefit of earlier HAART treatment. Our findings also raise the possibility that use of HAART without interruptions may reduce the incidence of these complications.