HIV drug resistance acquired through superinfection.
OBJECTIVE
HIV interclade B superinfection has previously been described in individuals initially infected with drug resistant virus who then become superinfected by a drug susceptible strain. We report an individual initially infected with a drug-sensitive clade B strain of HIV who was superinfected with another clade B strain resistant to two classes of antiretroviral drugs.


METHODS
To differentiate superinfection from possible co-infection we applied three independent molecular techniques: dye-primer sequencing of a pol fragment, length polymorphism analysis of the V4-5 coding region of the env gene and clonal sequencing of the V3 coding region of the env gene. To assess viral fitness we performed replication capacity assays of the pol gene.


RESULTS
These investigations supported the conclusion that this was a case of superinfection and not co-infection. Coincident with acquiring the new strain, the individual's viral load increased by about 10,000 copies/ml with a decrease of 150 x CD4 T cells/mul over the next 6 months. The greater in vivo fitness of the second virus was not supported by the replication capacity assay. Furthermore, superinfection negatively impacted this individual's treatment course. It was not known that he had acquired a drug resistant strain before entering a treatment study, and he had an incomplete response to therapy most likely because the superinfecting viral strain had a decreased susceptibility to two of the prescribed medications.


CONCLUSIONS
HIV drug resistance acquired through superinfection significantly lowers the likelihood of successful antiretroviral therapy and undermines the clinical value of a patient's prior drug resistance testing and lack of prior antiretroviral use.
Smith
Davey M
DM
University of California San Diego, USA. d13smith@ucsd.edu
Wong
Joseph K
JK
Hightower
George K
GK
Ignacio
Caroline C
CC
Koelsch
Kersten K
KK
Petropoulos
Christos J
CJ
Richman
Douglas D
DD
Little
Susan J
SJ
D000328:Adult; D018432:Drug Resistance, Multiple; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000032:analysis; D015163:Superinfection / Q000150:complications*
D012367:RNA, Viral