3rd International Workshop on HIV Drug Resistance 2-5 August 1994, Kauai, Hawaii, USA

RELATIONSHIP OF SI/NSI STATUS TO DEVELOPMENT OF ZDV RESISTANCE AND CLINICAL OUTCOMES IN PATIENTS ON ZDV THERAPY

Int Wkshop HIV Drug Res 1994 Aug 2-5;3:48 (abstract no. 47)

Douglas L. Mayers, K.F. Wagner, R.C.Y. Chung, M.T. Vahey, O.S. Weislow, J.L. Lennox, S.Y.J. Zhou, D.S. Burke and the RV 43 STUDY GROUP
Military Medical Consortium for Applied Retroviral Research, Rockville, MD,USA

OBJECTIVES: To determine the clinical and virologic parameters associated with the development of drug resistance, new opportunistic infections and death in a cohort of 100 patients with < 400 CD4 cells (mean 252±104 CD4 cells pre-rx) initially treated with zidovudine (ZDV) monotherapy.

METHODS: Patients were evaluated every 3 months with CD4 counts and drug susceptibility of their HIV isolates. Drug susceptibility testing was performed using the ACTG/DoD assay. Mutations at RT codon 215 were detected using nested PCR or RT-PCR. Viral burden (pRNA) was assessed using RT-PCR of pt plasma. SI phenotype was determined on MT-2 cells.

RESULTS: The cohort has experienced significant clinical decline with 59 patients developing ZDV-resistant (ZDV^®) virus, 30 new opportunistic infections (0I) and 27 HIV-related deaths. Factors associated with development of ZDV^® virus by Kaplan-Meier survival analysis included SI phenotype, CD4 cell count, platelet count and log₁₀ plasma HIV RNA. Factors which were associated with new 0I or death included hematocrit, CD4 cell count, log₁₀ plasma HIV RNA and ZDV IC₅₀. Multivariate Cox models were used to evaluate the relative importance of individual parameters for time to failure.

CONCLUSIONS: SI phenotype has been associated with more rapid CD4 decline ~ and rapid emergence of ZDV resistance in HIV-infected patients. There was no significant relationship of SI phenotype with either development of new 4 OIs or death in this cohort of patients. These anomalous results need to be reconciled to understand the mechanisms of clinical failure on ZDV monotherapy.

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1994-08-02
47

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