AEGiS-14CROI [37]: HIV-related Immune Suppression after ART Predicts Risk of Non-opportunistic Diseases: Results from the FIRST Study

14th Conference on Retroviruses and Opportunistic Infections

Los Angeles, California - February 25-28, 2007

HIV-RELATED IMMUNE SUPPRESSION AFTER ART PREDICTS RISK OF NON-OPPORTUNISTIC DISEASES: RESULTS FROM THE FIRST STUDY

Conf Retrovir Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 37)

Jason Baker^1,2, G Peng¹, J Rapkin¹, D Abrams³, M Silverberg⁴, W Cavert¹, R MacArthur⁵, W Henry^1,2, J Neaton¹, and Terry Beirn Community Prgms for Clin Res on AIDS (CPCRA)
¹Univ of Minnesota, Minneapolis, US; ²Hennepin County Med Ctr, Minneapolis, MN, US; ³Univ of California, San Francisco, US; ⁴Kaiser Permanente, Oakland, CA, US; and ⁵Wayne State Univ, Detroit, MI, US

BACKGROUND: Observational data suggest that the risk of death from non-opportunistic diseases (OD) during HIV infection may be related to immunosuppression. The SMART study showed that episodic ART led to increased risk of cardiovascular (CV), renal, and liver complications compared to continuous ART. The association of HIV-related immune suppression with specific non-fatal and fatal non-OD events after ART has not been well described. We compared the association between latest CD4 level (prior to event) and non-OD events (liver, CV, renal, cancer) using follow-up data from FIRST (substudy CPCRA 058).

METHODS: In FIRST, ART-naïve patients were randomized to 1 of 3 ART strategies (non-nucleoside reverse transcriptase inhibitors [NNRTI] + NRTI, protease inhibitors [PI] + NRTI, and 3-class therapy). Fatal and non-fatal OD and non-OD events were collected over a 5-year median follow-up and reviewed by an Endpoint Committee. OD events were defined by modified CDC AIDS criteria. Non-OD events included: liver (cirrhosis and grade 4 transaminitis); CV (myocardial infarction, stroke, or coronary artery disease requiring surgery); renal (end-stage renal disease or renal insufficiency); non-OD cancers (malignancy excluding non-Hodgkin’s lymphoma and Kaposi’s sarcoma). Cox models examined the association of OD and non-OD events with latest (time-updated) CD4 count (hazard ratio [HR] represent the difference in risk for a 100 cell higher CD4 count).

RESULTS: Of 1397 persons randomized in FIRST, median entry CD4 was 163 cells/mL, with an average increase of 238 cells/mL during follow-up; CD4 changes and OD rates did not vary by treatment. Univariate and multivariate associations with latest CD4 levels are described (table). HR for non-OD events, combined and individually, indicate risk of event is reduced when CD4 count is higher.

Event	OD	Non-OD	Liver	CV	Renal	Non-OD Cancer
# of Events	226	166	86	21	38	32
Univariate HR/100	0.50	0.79	0.77	0.86	0.76	0.80
cells	0.45,0.54	0.74,0.84	0.70,0.85	0.72,1.02	0.66,0.88	0.69,0.93
95%CI	<0.01	<0.01	<0.01	0.08	<0.01	<0.01
p-value
*Multivariate HR/100	0.58	0.81	0.76	0.78	0.92	0.83
cells	0.52,0.66	0.73,0.89	0.67,0.88	0.61,1.01	0.76,1.11	0.66,1.03
95%CI	<0.01	<0.01	<0.01	0.06	0.40	0.08
p-value

*adjusted for: age, sex, race, prior AIDS, hepatitis B and C, baseline CD4 & RNA, and latest RNA

CONCLUSIONS: Higher, latest CD4 count was associated with a reduced risk of non-OD events (liver, CV, renal, and cancer), though to a lesser degree than with OD events. These data suggest that treatment strategies minimizing the time spent at lower CD4 counts will prevent both non-OD and OD events.

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2007-02-25
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