HIV Drug Resistance Acquired Through Superinfection
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 and Design: 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 × CD4 T cells/µl 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.
Conclusion: 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.
Superinfection with HIV is presumed to occur frequently because of the prevalence of interclade recombinants. However, documented superinfection in humans has only recently been reported, first with different clades and subsequently, two instances of intraclade B superinfection. Koelsch et al. reported a patient who was initially infected with drug-resistant HIV and then secondarily infected by drug-sensitive ('wild-type') virus. The superinfecting wild-type HIV replicated at high levels and masked from standard drug resistance tests the underlying presence of the initial drug-resistant virus. We now report a patient initially infected with a drug-sensitive clade B strain of HIV who was superinfected with another clade B strain resistant to two important classes of antiretroviral drugs.
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 and Design: 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 × CD4 T cells/µl 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.
Conclusion: 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.
Superinfection with HIV is presumed to occur frequently because of the prevalence of interclade recombinants. However, documented superinfection in humans has only recently been reported, first with different clades and subsequently, two instances of intraclade B superinfection. Koelsch et al. reported a patient who was initially infected with drug-resistant HIV and then secondarily infected by drug-sensitive ('wild-type') virus. The superinfecting wild-type HIV replicated at high levels and masked from standard drug resistance tests the underlying presence of the initial drug-resistant virus. We now report a patient initially infected with a drug-sensitive clade B strain of HIV who was superinfected with another clade B strain resistant to two important classes of antiretroviral drugs.
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