565-T. Longitudinal Analysis of RT and Protease Mutations among Israeli Patients Infected with HIV Subtype C

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Session 75 Poster Session
Resistance to Antiretroviral Chemotherapeutic Agents
Session Time: 4:30-6:30 pm
Room 4E-F

565-T.

Longitudinal Analysis of RT and Protease Mutations among Israeli Patients Infected with HIV Subtype C
Z. Grossman*¹, S. Maayan², D. Auerbuch², E. Sahar³, I. Levi⁴, M. Lorber³, G. Gottesman⁵, K. Rizenfeld⁶, M. Chowers⁵, Z. Kra-Oz², E. Mendelson¹, Z. Bentwich⁷, M. Elkan⁶, D. Engelhard², S. Polak³, I. Yust⁸, and J. M. Schapiro⁹ for Israel Multi-Ctr. AIDS Study Group
¹Publ. Hlth. Lab.; ²Hadassah Univ. Hosp.; ³Rambam Med. Ctr.; ⁴Sheba Med. Ctr.; ⁵Meir Med. Ctr.; ⁶Soroka Med. Ctr.; ⁷Kaplan Med. Ctr.; ⁸Soraski Med. Ctr.; and ⁹Natl. Hemophilia Ctr., Israel

Methods: We performed a longitudinal study of HIV clade C patients following their development of resistance mutations while receiving therapy and compared these to our clade B patients. Samples with VL >1000 were sequenced (VGI). Patients had 2 or more sequential tests performed.
Results: 91 plasma samples from 41 clade C patients were analyzed. Of these, in 12 the initial sample was taken prior to HAART, in 15 during the first year of HAART and in 11 >1 year. The mean follow-up time was 31 (4-62) months. Data were compared with 81 samples from 67 local clade B patients. The mean VL was 5.3 (3.0-6.7) log₁₀ copies/mL, mean CD4 361 (11-1210) cells/ľL. The most common drug combinations included AZT+3TC (23 patients, 32 samples), NFV (13 patients, 20 samples), and IDV (10 patients, 15 samples). Drug use, VL, and CD4 values were similar in the clade B and C groups, but more B patients received EFV (23% vs 4.5%), and more children were in the clade C group (8 vs 0). The longest drug exposure times documented as first line treatments were AZT/3TC (17 patients, mean follow-up 13.1ą1.8 m), to Nelfinavir (13 patients, mean follow-up 10ą1 m), and Indinavir (8 patients, mean follow-up 11.2ą1.7 m). Characteristic primary and secondary PI resistance mutations developed in both groups, although 10I/V, 30N, 63P 71V/I, 77I and 90M were significantly higher in B, and 36I, 41K, 69K, 89M, and 93L in C (p < 0.001 for all). Patients were commonly on ZDV/3TC as the first line of NRTI. 33% and 51% of samples of clade B and C, respectively, received ZDV (p<0.03) the frequency of characteristic ZDV mutations (or NAMS: 41, 67, 70, 210, 215, 219) were significantly higher (p<0.02) for all except L210W (p<0.08) in B compared to C. No significant difference was found in the frequency of M184V between the 2 groups (p=0.333).
Conclusions: During antiretroviral therapy mutations frequently arise in clade C and appear to follow a general pattern similar to that in clade-B-infected patients. The background mutations in the protease differ in C vs B. The clinical significance is not known. The M184V/I mutation rate was similar in C and B while the characteristic ZDV mutations rate was somewhat lower in C. To what degree this was due to adherence or other factors remains to be determined.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections