The role of HIV type 1 phenotype and genotype in long-term responders to zidovudine therapy.
We performed a cross-sectional and partly retrospective virological evaluation of 31 long-term responders (LTRs) to zidovudine (ZDV) (persistent increase in the CD4+ cell counts without progression of HIV infection throughout a period of ZDV therapy > 3 years) and 17 well-matched controls who developed a marked immunological deterioration over a 24-month period of ZDV therapy. The biological phenotype of HIV-1 was assessed 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 215 and 41 of RT were checked in proviral DNA from uncultured PBMCs. Show/low non-syncytium-inducing (S/L-NSI) and rapid/high syncytium-inducing (R/H-SI) variants were detected in 25 (81%) and 2 (6%) LTRs, respectively. HIV-1 could not be isolated in the remaining four LTRs (13%). Conversely, 12 of 17 (71%) controls yielded R/H-SI variants. Conversion from the S/L-NSI to R/H to R/H-SI phenotype occurred in 5 controls but in none of the 18 LTRs tested. Mutant sequences in proviral DNA from control 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 benefits even after prolonged ZDV treatment had S/L-NSI viruses and a low risk to develop ZDV resistance. Conversely, subjects who demonstrated an 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 develop mutations indicating ZDV resistance.
Angarano
G
G
Clinic of Infectious Diseases, University of Bari, Italy.
Monno
L
L
Vivirito
M C
MC
Appice
A
A
Romanelli
C
C
Giannelli
A
A
La Grasta
L
L
Fracasso
C
C
Fiore
J R
JR
Milazzo
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000235:genetics / Q000821:virology*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004352:Drug Resistance, Microbial; D005260:Female; D005838:Genotype; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D016296:Mutagenesis; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D017741:Survivors; D015215:Zidovudine / Q000627:therapeutic use*
D015215:Zidovudine