HIV-1 proviral resistance mutations: usefulness in clinical practice.
OBJECTIVE
Transmitted HIV strains may harbour drug resistance mutations. HIV-1 drug resistance mutations are currently detected in plasma viral RNA. HIV-1 proviral DNA could be an alternative marker, as it persists in infected cells.


METHODS
This was a prospective study assessing the prevalence and persistence of HIV-1 drug resistance mutations in DNA from CD4 cells before and after protease inhibitor (PI)- or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy initiation in 69 drug-naïve patients.


RESULTS
Before therapy, 90 and 66% of detected mutations were present in CD4 cells and plasma, respectively. We detected seven key mutations, and four of these (M184M/V, M184M/I, K103K/N and M46M/I) were only found in the cells. When treatment was started, 40 patients were followed; the mutations detected at the naïve stage remained present for at least 1 year. Under successful treatment, new key mutations emerged in CD4 cells (M184I, M184M/I and Y188Y/H).


CONCLUSIONS
The proportion of mutations detected in the DNA was statistically significantly higher than that detected in standard RNA genotyping, and these mutations persisted for at least 1 year irrespective of therapy. The pre-existence of resistance mutations did not jeopardise treatment outcome when the drug concerned was not included in the regimen. Analysis of HIV-1 DNA could be useful in chronic infections or when switching therapy in patients with undetectable viraemia.
Kabamba-Mukadi
B
B
Université Catholique de Louvain, AIDS Reference Laboratory, Brussels, Belgium. benoit.Kabamba@uclouvain.be
Duquenne
A
A
Henrivaux
P
P
Musuamba
F
F
Ruelle
J
J
Yombi
J-C
JC
Bodéus
M
M
Vandercam
B
B
Goubau
P
P
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; 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 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D015995:Prevalence; D011446:Prospective Studies; D011533:Proviruses / Q000235:genetics*; D012367:RNA, Viral / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D019562:Viral Load; D055815:Young Adult
D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D012367:RNA, Viral