THE ROLE OF HIV TYPE-1 PHENOTYPE AND GENOTYPE IN LONG-TERM RESPONDERSTO ZIDOVUDINE THERAPY

We performed a cross-sectional and partly retrospective virological ev aluation of 31 long-term responders (LTRs) to zidovudine (ZDV) (persis tent increase in the CD4(+) cell counts without progression of HIV inf ection throughout a period of ZDV therapy >3 years) and 17 well-matche d controls who developed a marked immunological deterioration over a 2 4-month period of ZDV therapy. The biological phenotype of HIV-1 was a ssessed by testing the capacity of the isolates to replicate in the MT -2, HUT-78, C-8166, and U-937 T cell lines, and mutations at codons 21 5 and 41 of RT were checked in proviral DNA from uncultured PBMCs. Slo w/low non-syncytium-inducing (S/L-NSI) and rapid/high syncytium-induci ng (R/H-SI) variants were detected in 25 (81%) acid 2 (6%) LTRs, respe ctively, HIV-1 could not be isolated in the remaining four LTRs (13%), Conversely, 12 of 17 (71%) controls yielded R/H-SI variants, Conversi on from the S/L-NSI to WH-SI phenotype occurred in 5 controls but in n one of tile 18 LTRs tested, Mutant sequences in proviral DNA from cont rol PBMCs were consistently detected (94%), while a wild-type sequence of the residues investigated was found in the majority of LTRs (77%). In our series, patients who received immunological and clinical benef its even after prolonged ZDV treatment had S/L-NSI viruses and a low r isk to develop ZDV resistance, Conversely, subjects who demonstrated a n immunological and clinical deterioration yielded R/H-SI variants or shifted from S/L-NSI to R/H-SI phenotypes and were at higher risk to d evelop mutations indicating ZDV resistance.