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3rd International Workshop on HIV Drug Resistance2-5 August 1994, Kauai, Hawaii, USA |
NOVEL MUTATIONS ASSOCIATED WITH A RAPID DECLINE IN CD4 CELLS COUNT
Int Wkshop HIV Drug Res 1994 Aug 2-5;3:50 (abstract no. 49)
Ruiz, L.1, Erice, A.2, Gómez, M.1, Sannerud, K.2 and B. CLotet1
1RetroviroLogy Laboratory. Hospital Universitari "Germans Trias Pujol". Badalona. Barcelona. Spain; 2Department of Laboratory Medicine and Pathology. University of Minnesota. Medical School. Minneapolis. Minnesota. U.S.A.
OBJECTIVE: To describe the heterosexual transmission of a mutant strain non resistant to ZDV, but associated with a rapid decline in CD4 cells count, in spite of antiretroviral therapy.
Patients: Donor is a white haemophiliac male, 23 years old. The patient has been seropositive since 1988 and the CD4 cells count are 190/mm3. The patient has been treated with AZT for 18 months and remains asymptomatic. Recipient is a white female of 22 years. She has been seropositve since January 1993 although earlier determinations of anti-HIV antibodies over the previous 12 months were negative. In April 1993 her CD4 count was 200/mm3, which indicates a rapid decrease. The patient was never treated with ZDV.
METHODS: The IC50 were determined by consensus method of the AIDS Clinical Trials Group. SI phenotype was determined by the ability to grow in MT-2 cells. A nested PCR was used to detect the mutations associated with ZDV resistance at RT codon 215. We performed polymerase chain reaction (PCR) mediated by direct sequencing of the RT coding region in peripheral blood in both patients.
RESULTS: The strains were sensitive to ZDV susceptibility assays (IC50 <0.1 µM). The isolated strains were non inducers of syncytium (NSI). The samples were “wild type” with the nested PCR for associated mutations for resistance to ZDV. The direct sequencing for the isolates, although they coincided with the genotype results for PCR, demonstrated the presence of two mutations, not previously described, in the 177 and 178 codon of the RT in both donor and recipient.
CONCLUSION: The appearance of mutations, not associated to ZDV resistance, can influence the CD4 cells count and a more rapid progression of the disease. This could be related to different parameters, amongst which could be cellular factors particular to each host, which regulate the replication of HIV, together with cellular and/or humoral immunity, etc. Its expression as poorer prognosis of the disease shows us once again that it does not only depend on the type of strain that is transmitted, but also depends on the immunity and cellular mechanisms of the host. It is necessary to sequence the gene which codifies for RT in a large number of infected patients to estimate the real significance of all the mutations.
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1994-08-02
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