Viral load, viral phenotype modification, zidovudine susceptibility and reverse transcriptase mutations during the first 6 months of zidovudine monotherapy in HIV-1-infected people.
We studied 14 zidovudine-naive, HIV-1-infected patients attending an infectious diseases clinic in Milan during zidovudine therapy for 6 months. We monitored CD4 cell counts, immune complex-dissociated p24 antigen, viral phenotype and viral load in plasma. The virus infecting a subset of patients was examined for zidovudine susceptibility and zidovudine resistance-associated mutations. A significant correlation was established between the increase in the CD4 cell count and the decrease in viral load (Spearman's coefficients < -0.5). Patients who were p24 antigen positive had a higher viral load (P < 0.005 at baseline and after 6 months of therapy). Patients with non-syncytium-inducing (NSI) virus had higher CD4 cell counts over time than those with syncytium-inducing (SI) virus. We also examined the viral load in relation to viral phenotype. The median viral load in patients with NSI virus was higher than in SI controls at baseline, but not after 3 and 6 months of therapy. Sequential isolates of HIV-1 were obtained from nine patients and tested for resistance to zidovudine by monitoring the drug susceptibility and the reverse transcriptase-encoding sequence. Amino acid changes at codons 70 and 215 were present in some but not all isolates with zidovudine-resistant phenotype in vitro. It was possible to perform a correlation between zidovudine susceptibility and zidovudine-associated pol gene mutations only at the 6-month time point (Spearman's coefficient = 0.076). SI phenotype was associated with the development of a decreased zidovudine susceptibility. A correlation between zidovudine-associated pol gene mutations and SI phenotype was detected at the 6-month time point.
Rusconi
S
S
Clinica delle Malattie Infettive, Universitá di Milano, Ospedale Luigi Sacco, Italy. rusconi@imiucca.csi.unimi.it
De Pasquale
M P
MP
Mainini
F
F
Bulgheroni
E
E
Kurtagic
S
S
Gori
A
A
Violin
M
M
Zanchetta
N
N
Moroni
M
M
Balotta
C
C
Galli
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016655:HIV Core Protein p24 / Q000097:blood; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009154:Mutation; D010641:Phenotype; D013997:Time Factors; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D015215:Zidovudine; D054303:HIV Reverse Transcriptase