Dynamics of 103K/N and 184M/V HIV-1 drug resistant populations: relative comparison in plasma virus RNA versus CD45RO+T cell proviral DNA.
BACKGROUND
Viral populations defined by 103K/N and 184M/V as linked or single mutations in the HIV-1 reverse transcriptase gene were investigated in plasma samples and compared with previous findings in the CD45RO(+)T cell compartment.


OBJECTIVE
To develop an ARMS assay for plasma virions and to investigate the expression of resistance mutations (103N and 184V) and dynamic interactions between proviral DNA and plasma virions.


METHODS
A clinical cross-sectional study, including 11 patients on lamivudine efavirenz and/or nevirapine therapy. The viral populations were determined by an assay based on real-time PCR and amplification refractory mutation system (ARMS).


RESULTS
The 103N and 184V mutations were not detected in patients with stable low viremia. Patients previously exposed to mono or dual therapy often carried minor viral populations of either one or both mutations in plasma. The viral population with linked mutations (103N and 184V) was detected in two patients after more than 2 years of non-NNRTI HAART.


CONCLUSIONS
The ARMS assay is useful for detecting viral quasi-species containing efavirenz and lamivudine resistant mutations in plasma virions and in proviral DNA. Data suggest an unequal distribution of linked-mutation populations in plasma and CD45RO(+)T cells. Furthermore, the linked 103N-184V mutation may be more fit than the single 184V mutation and this linked population emerges rapidly under inadequate drug pressure.
Jakobsen
M R
MR
Department of Infectious diseases, Aarhus University Hospital, Skejby Sygehus, Brendstrupgaardvej 100, 8200 Aarhus N, Denmark. mrj@sks.aaa.dk
Tolstrup
M
M
Bertelsen
L
L
Laursen
A
A
Obel
N
N
Ostergaard
L
L
Mohey
R
R
D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use; D048588:Benzoxazines / Q000627:therapeutic use; D003521:Cyclopropanes; D004279:DNA, Viral / Q000097:blood* / Q000302:isolation & purification; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D017493:Leukocyte Common Antigens / Q000378:metabolism; D009154:Mutation; D019829:Nevirapine / Q000627:therapeutic use; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D011533:Proviruses / Q000235:genetics / Q000502:physiology; D012367:RNA, Viral / Q000097:blood* / Q000302:isolation & purification; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D014766:Viremia / Q000821:virology
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004279:DNA, Viral; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; D017493:Leukocyte Common Antigens; C098320:efavirenz