Virological and immunological analysis of a triple combination pilot study with loviride, lamivudine and zidovudine in HIV-1-infected patients.
OBJECTIVE
To compare two antiretroviral regiments, loviride plus lamivudine (3TC) plus zidovudine (ZDV) (triple combination) and loviride plus ZDV (double combination) in terms of pharmacokinetic interactions, tolerability, safety, and immunological and virological efficacy.


METHODS
An open, case-controlled, pharmacokinetic and 24-week continuous treatment pilot study.


METHODS
Twenty p24 antigen-positive patients, 10 per treatment group, were matched according to p24 antigenaemia less or more than 100 pg, CD4 count less or more than 150 x 10-(6)/l, and gender. Eight out of 10 cases and seven out of 10 controls had received previous antiretroviral therapy.


RESULTS
No clinically relevant pharmacokinetic interactions were observed. Both treatment combinations were well tolerated. Median absolute and percentage CD4 count increases above baseline were more pronounced in the triple combination arm than in the double combination arm. Median p24-antigen and plasma viraemia level decreases below baseline were more pronounced in the triple combination arm. The M(184)I/V mutation was detected in all plasma samples of triple combination patients examined at week 12. Mutations conferring resistance to loviride and ZDV were found in a significant subset of patients in both treatment arms.


CONCLUSIONS
Both combination regimens have an excellent safety/tolerability profile, but a higher level of in vivo efficacy is achieved by the triple combination, despite genotypic changes conferring resistance to one or all of these agents. The conclusions drawn are limited by small population size and the heterogenous pretreatment history. However, they support the validity of and strongly encourage a rationally designed multidrug combination approach to HIV therapy.
Staszewski
S
S
Johann Wolfgang Goethe University, Frankfurt, Germany.
Miller
V
V
Rehmet
S
S
Stark
T
T
De Crée
J
J
De Brabander
M
M
Peeters
M
M
Andries
K
K
Moeremans
M
M
De Raeymaeker
M
M
Pearce
G
G
Van den Broeck
R
R
Verbiest
W
W
Stoffels
P
P
D000081:Acetamides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000098:Acetophenones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D018592:Cross-Over Studies; D004252:DNA Mutational Analysis; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019259:Lamivudine; D008875:Middle Aged; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D016047:Zalcitabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015215:Zidovudine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000081:Acetamides; D000098:Acetophenones; D000998:Antiviral Agents; D016655:HIV Core Protein p24; D012367:RNA, Viral; D019259:Lamivudine; C080073:loviride; D015215:Zidovudine; D016047:Zalcitabine