Persistence of HIV-1 drug resistance mutations and emergence during antiretroviral treatment interruption: considerations from a clinical case.
BACKGROUND
HIV drug resistance (HDR) represents a crucial problem in antiretroviral therapy today. HDR mutations can accumulate, persist in the proviral genome and re-emerge, promoting further failure of rescue regimens. Resistance testing on the proviral genome has been suggested in order to detect the presence of archived resistance mutations and to guide drug prescription.


METHODS
We report the persistence of HDR mutations to protease inhibitors (PIs) during effective highly active antiretroviral therapy (HAART) not including PIs and their transient re-emergence after treatment interruption. Further follow-up has demonstrated a progressive reversion toward the wild type. At that point in time, proviral DNA analysis was not more sensitive in detecting mutations than tests of the plasma viral load.


CONCLUSIONS
This case demonstrates that HDR mutations can persist even though plasma viral load is undetectable, implying the ability of HIV to escape from treatment recycling and the use of drugs to which HIV is cross-resistant. Also, this case suggests that plasmatic and intracellular HIV compartments find a balance under conditions of active viral replication, which could hamper detection of resistance mutations in the proviral DNA. Therefore, in the case of active viral replication, proviral analysis may not actually provide more information than testing the plasma viral load. The clinical utility and specific indications for testing proviral DNA require further investigation.
Torti
Carlo
C
Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy. carlotorti@hotmail.com
Moretti
Francesca
F
Uccelli
Maria C
MC
Tirelli
Valeria
V
Quiros-Roldan
Eugenia
E
Gargiulo
Franco
F
Carosi
Giampiero
G
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D013997:Time Factors; D017211:Treatment Failure
D019380:Anti-HIV Agents; D004279:DNA, Viral