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Plasma human immunodeficiency virus (HIV) type 1 RNA levels, CD4 lymphocyte changes, and drug resistance were studied in HIV-infected patients with 200-500 CD4 lymphocytes/microL who received zidovudine and didanosine combination therapy for 2 years. Among 35 patients, 10 had sustained and 16 had transient > 10-fold reductions in HIV RNA: 9 did not have 10-fold HIV RNA reductions. Only patients with sustained HIV suppression maintained increased CD4 cell counts for 2 years (370 to 501 cells/microL; P = .006). Patients with transient HIV suppression were more likely to develop drug-resistant HIV strains (12/16 vs. 5/19, P = .01) and reverse transcriptase (RT) mutations (4.5 vs. 2.5/strain; P = .02) than were patients with sustained or no HIV suppression. Zidovudine resistance occurred with RT mutations at codons 41, 67, 70, 215, and 219. Multidrug resistance occurred with mutations at codons 62, 75, 77, 116, and 151. Mutations occurred at codons 60, 68, 118, 210, and 228 in > or = 4 patients each. Heterogeneity exists among individual virologic responses to zidovudine and didanosine combination therapy. HIV resistance mechanisms during combination therapy appear more complex than reported with monotherapy.

Original publication




Journal article


J Infect Dis

Publication Date





70 - 78


Amino Acid Sequence, Base Sequence, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Codon, DNA Primers, Didanosine, Drug Resistance, Microbial, Drug Resistance, Multiple, Drug Therapy, Combination, HIV Infections, HIV Reverse Transcriptase, HIV-1, Humans, Molecular Sequence Data, Point Mutation, Polymerase Chain Reaction, RNA, Viral, RNA-Directed DNA Polymerase, Zidovudine