Virological and immunological stability in HIV infected patients undergoing partial-treatment interruption.
BACKGROUND
Partial-treatment interruption in patients with drug-resistant viremia has been associated with stable HIV RNA levels suggesting that interruption of protease inhibitors may be an effective strategy for patients without other therapeutic options while waiting for the development of new drugs.


OBJECTIVE
Our goal was to maintain virological and immunological stability in patients experiencing virologic failure with multiresistant HIV to allow access to newly developed antiretroviral drugs, and to characterize the impact of partial-treatment interruption on replication capacity and resistance profile.


METHODS
From 2003 to 2004, a group of 12 heavily treated patients was studied. Protease inhibitor treatment was interrupted and patients were treated with nucleoside analog retrotranscriptase inhibitors (Trizivir) and the fusion inhibitor Enfurvirtide to establish the therapeutic benefit and the virologic response.


RESULTS
Both, CD4 T-cell counts and viral load remained stable for a period of time that enabled all the patients to access rescue treatments (median=13.5 months; IQR: 9-19). The replication capacity of the patient-derived viruses significantly decreased or remained stable during the partial-treatment interruption. The decrease in replication capacity was mainly attributable to the selection of viruses carrying at least two fewer minor mutations in the protease. As of December 2008 10 of 12 patients maintained undetectable HIV RNA levels.


CONCLUSIONS
Study results indicate that a partial-treatment interruption regimen based on Trizivir with Enfurvirtide augmentation allows for a loss of protease inhibitor resistance mutations as well as for a decrease in the replication capacity of patient-derive HIV protease gene recombinants.
Mata
Rosario C
RC
Servicio de Enfermedades Infecciosas, Hospitales Universitarios Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain.
Flor-Parra
Fernando
F
Viciana
Pompeyo
P
López-Cortés
Luis F
LF
Pérez-Romero
Pilar
P
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004338:Drug Combinations; D024882:Drug Resistance, Viral; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D028761:Withholding Treatment; D015215:Zidovudine / Q000627:therapeutic use; D000099227:Abacavir
D019380:Anti-HIV Agents; D004338:Drug Combinations; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41; D017320:HIV Protease Inhibitors; D019259:Lamivudine; D010446:Peptide Fragments; D015215:Zidovudine; C418262:abacavir, lamivudine, and zidovudine drug combination; D000099227:Abacavir