Analysis of a long-term discrepancy in drug-targeted genes in plasma HIV-1 RNA and PBMC HIV-1 DNA in the same patient.
Drug-resistance genotypes were investigated in a patient under treatment with anti-HIV drugs. Since the drug resistance-associated mutations in plasma HIV-1 RNA and proviral DNA in peripheral blood mononuclear cells (PBMCs) were inconsistent, changes were followed over time, and the discrepancy was shown to persist for a long period. In plasma HIV-1 RNA, D67N, K70R, T215Y, and Y188L were present in the reverse transcriptase (RT) region, and two primary mutations, I84V and L90M, were noted in the protease (Pro) region. In contrast, in proviral DNA, no drug resistance-associated mutations were found in the RT region, and mutations such as L90L/M were only infrequently present in the Pro region. This situation persisted for more than 3 years. In addition, sequencing analysis of the V3 loop in the envelope gene showed that non-syncytium-inducing/macrophage-tropic viruses contribute to acquisition of drug resistance. In this study, drug-resistant viruses were produced primarily at macrophages, and drug-sensitive viruses were maintained in PBMCs as a reservoir.
Usuku
Shuzo
S
Department of Testing and Reserach, Yokohama City Institute of Health, Kanagawa 235-0012, Japan. sh00-usuku@city.yokohama.jp
Noguchi
Yuzo
Y
Sakamoto
Mitsuo
M
Adachi
Takuya
T
Sagara
Hiroko
H
Sudo
Koji
K
Nishizawa
Masako
M
Kondo
Makiko
M
Tochikubo
Osamu
O
Imai
Mitsunobu
M
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D004279:DNA, Viral / Q000097:blood* / Q000235:genetics; D004197:Disease Reservoirs / Q000821:virology; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood* / Q000235:genetics; D012189:Retrospective Studies; D019562:Viral Load; D014766:Viremia
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral