Targeting only reverse transcriptase with zidovudine/lamivudine/abacavir plus tenofovir in HIV-1-infected patients with multidrug-resistant virus: a multicentre pilot study.
OBJECTIVE
To evaluate the safety, immunological outcome and HIV-1 evolution in the reverse transcriptase (RT) in patients with multidrug resistance receiving zidovudine/lamivudine/abacavir (TZV) plus tenofovir (TDF).


METHODS
Pilot analysis of highly experienced patients (n=28), with > or =1 thymidine-associated mutation (TAM) and the M184V mutation.


RESULTS
Median of 8.5 treatment regimens, 58% Centers for Disease Control stage C. Baseline (nadir) CD4 count 363 (112) cells/microL. There was a sustained 24-week drop in viral load (VL) of 0.71 HIV-1 RNA copies/mL (P<0.001), with 35.7% (10/28) achieving a VL of <50 copies/mL. The median 24-week decrease in CD4 was -53 cells/microL and only-17 cells/microL when baseline CD4 was <350 cells/microL. There was no evolution in RT mutations, TAMs, accessory mutations or K65R. No clinical progression and one out of 28 suspected abacavir Hypersensitivity Reaction (HSR). Lower probability of achieving VL<400 copies/mL was associated with D67N (P=0.007), D67N/M41L (P=0.01), > or =3 TAMs (P=0.07) and VL>10 000 copies/mL (P=0.01). Mutations conferring zidovudine hypersusceptibility (Y181C, K65R and L74V) did not improve virological or immunological outcomes. Better CD4 outcomes were seen in patients without M41L (P=0.04) or with baseline VL<10,000 copies/mL (P=0.01).


CONCLUSIONS
A bridging regimen with TZV+TDF prevents significant immunological decline and may forestall viral evolution in HIV-1 RT despite persistent viral replication.
Llibre
J M
JM
Lluita contra la SIDA Foundation, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain; Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain. jmllibre@flsida.org [corrected]
Bonjoch
A
A
Iribarren
J
J
Galindo
M J
MJ
Negredo
E
E
Domingo
P
P
Pérez-Alvarez
N
N
Martinez-Picado
J
J
Schapiro
J
J
Clotet
B
B
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides / Q000627:therapeutic use; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects* / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D010865:Pilot Projects; D012367:RNA, Viral / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000068698:Tenofovir; D013936:Thymidine / Q000235:genetics; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D054303:HIV Reverse Transcriptase; D019259:Lamivudine; D063065:Organophosphonates; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D013936:Thymidine; D015215:Zidovudine; D000099227:Abacavir; C514824:reverse transcriptase, Human immunodeficiency virus 1