Vertical transmission of multidrug-resistant human immunodeficiency virus type 1 (HIV-1) and continued evolution of drug resistance in an HIV-1-infected infant.
To confirm the vertical transmission of multidrug-resistant (MDR) human immunodeficiency virus type 1 (HIV-1) and to assess its impact on further evolution of drug-resistant virus in an infant, proviral DNA amplified from infected peripheral blood mononuclear cell cultures was sequenced to identify reverse transcriptase (RT) and protease (PR) mutations. The infant had proviral DNA with evidence of RT mutations (M41L, L74V, and T215Y) and 3 PR substitutions (K20R, M36I, and V82A). After delivery, the mother's proviral DNA had the same substitutions. Phylogenetic analyses of these HIV-1 RT and PR sequences indicated epidemiological linkage. Plasma drug susceptibility was determined by using a recombinant virus assay. Plasma HIV-1 obtained after the infant's birth demonstrated reduced susceptibility to zidovudine and ritonavir. Thus, vertical transmission of MDR HIV-1 was demonstrated in the setting of detectable maternal plasma viremia. Further accumulation of broad MDR in the infant's virus to 3 antiretroviral classes occurred, despite postnatal therapy.
Johnson
V A
VA
Division of Infectious Diseases, University of Alabama at Birmingham School of Medicine, Birmingham Veterans Affairs Medical Center, AL 35294-0006, USA. vjohnson@uab.edu
Petropoulos
C J
CJ
Woods
C R
CR
Hazelwood
J D
JD
Parkin
N T
NT
Hamilton
C D
CD
Fiscus
S A
SA
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D004352:Drug Resistance, Microbial / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000635:transmission / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008826:Microbial Sensitivity Tests; D016296:Mutagenesis; D009154:Mutation; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000821:virology*; D011480:Protease Inhibitors / Q000494:pharmacology; D011533:Proviruses / Q000235:genetics; D012189:Retrospective Studies; D019438:Ritonavir / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology
D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; D019438:Ritonavir