Application of HIV-1 genotypic-resistance testing prevents the evolution of further resistance mutations in heavily pretreated patients.
BACKGROUND
Resistance-associated mutations in HIV-1 evolve even under highly active antiretroviral therapy.


OBJECTIVE
To evaluate the clinical efficacy of genotypic-resistance testing (GRT), to estimate the potential of a given antiretroviral therapy for prevention of further resistance mutations.


METHODS
Ten patients were treated prospectively with drugs, according to the results of a GRT. Five patients were allocated to group I in which antiretroviral therapy could be switched to an effective regimen (consisting of at least three sensitive drugs, from at least two different classes of antiretroviral substances). Five patients (group II) had no option for effective therapy, and continued to be treated non-effectively (at least one applicated substance class only intermediately sensitive, or resistant). GRT and quantitative viral cultures were performed longitudinally for 8 months. Also, plasma HIV-1 RNA, total CD4+ cells, and rates of productively infected CD4+ cells were determined.


RESULTS
All the patients in group I showed a significant decrease of HIV-RNA of >1 log/ml (mean, -1.35 log/ml, P=0.025). The mean increase of CD4+ cells was 46 (not significant). The rate of productively infected CD4+ cells decreased significantly (mean, -16 productively infected CD4+ cells per 10(6) total CD4+ cells, P=0.04). In this group no further resistance mutations were detected after 8 months. In group II, none of the patients showed a significant decrease of HIV-1 RNA (mean, +0.05 log/ml), total CD4+ cells decreased (mean, -35, not significant), the rate of productively infected CD4+ cells increased significantly (mean, +124 productively infected CD4+ cells per 10(6) total CD4+ cells, P=0.04), and 4 of 5 patients had additional mutations in the RT gene conferring multi-drug resistance within 8 months (P=0.048).


CONCLUSIONS
GRT is predictive of the efficacy of a therapeutic regimen, in particular regarding evolution of further resistance mutations.
Institut für Medizinische Mikrobiologie und Immunologie, Universitätskrankenhaus Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
B
B
Zöllner
H H
HH
Feucht
L
L
Weitner
A
A
Adam
M
M
Schröter
P
P
Schäfer
R
R
Laufs
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003657:Decision Making; D004352:Drug Resistance, Microbial / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D012367:RNA, Viral