Divergent distribution of HIV-1 drug-resistant variants on and off antiretroviral therapy.
OBJECTIVE
To investigate the distribution of drug-resistant HIV-1 variants in plasma RNA and peripheral blood monuclear cell (PBMC) DNA at treatment failure while on therapy and after stopping therapy.


METHODS
Fifty-eight patients failing their first highly active antiretroviral treatment while on therapy and 50 patients after a median of 18.6 weeks after treatment interruption following multiple treatment failures were analysed.


METHODS
Paired plasma HIV-1 RNA and PBMC HIV-1 DNA were used for genotypic antiretroviral resistance testing. Drug resistance was computed by using the Stanford on-line genotype interpretation system.


RESULTS
The extent of drug resistance was larger in plasma RNA than in PBMC DNA in the on-therapy group (P=0.004) and in PBMC DNA than in plasma RNA in the off-therapy group (P=0.04). Interpretation of genotype based on PBMC DNA and plasma RNA in the on-therapy and in the off-therapy group would have missed detection of resistance to one or more drugs in 21 and 22% of the patients, respectively, compared to interpretation based on the other blood compartment. In a subset of 27 patients for whom a sample before stopping therapy was available, there was a significant decrease in the number of RNA (mean 8.1 to 5.3, P=0.004), but not DNA (mean 6.8 to 5.7, P=0.143), resistance mutations following treatment interruption.


CONCLUSIONS
While plasma RNA is the material of choice for early detection of drug resistance while on therapy, analysis of PBMC DNA may additionally support and possibly improve sensitivity of resistance testing in the absence of therapy.
Venturi
Giulietto
G
Sezione di Microbiologia, Dipartimento di Biologia Molecolare, Università di Siena, Siena, Italy.
Romano
Laura
L
Carli
Tiziana
T
Corsi
Paola
P
Pippi
Luigi
L
Valensin
Pier E
PE
Zazzi
Maurizio
M
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005838:Genotype; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D009154:Mutation; D012367:RNA, Viral / Q000097:blood
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral