Pravastatin in HIV-infected patients treated with protease inhibitors: a placebo-controlled randomized study.
OBJECTIVE
The objectives of the study were to assess the effects of pravastatin on plasma HIV RNA, lipid parameters, and protease inhibitor (PI) concentrations in patients treated with PI-containing regimens and with total cholesterol (TC) > or = 5.5 mmol/L.


METHODS
A clinical trial including patients randomized to receive pravastatin or matching placebo for 12 weeks was implemented.


RESULTS
Twelve patients were included in the pravastatin group and 9 in the placebo group. At week 12 (W12), no patient had experienced virological failure. Between week 0 (W0) and W12, the median differences for TC were -1.4 mmol/L in the pravastatin group and +0.2 mmol/L in the placebo group (p = .005); for LDL, they were -1.0 mmol/L and +0.3 (p = .007), respectively. A significant decrease of the PI concentration (12 hours after administration) ratio W12 - W0/W0 was noticed in the pravastatin group (-0.2 [interquartile range, -0.3 to -0.1] as compared with the placebo group (0.1 [IQR, 0.0 to 0.3]) (p = .03). When the study was restricted to patients treated with lopinavir/ritonavir, a decrease from 3.8 microg/mL at baseline to 2.9 mug/mL at W12 was noticed in the pravastatin arm (p = .04) but not in the control arm (p = 1.00). No clinical adverse event reached a severity of grade 3.


CONCLUSIONS
We observed in this study that the use of pravastatin in PI-treated patients was not associated with major change in the plasma HIV RNA on 12 weeks of follow-up. However, we found a trend of decrease of the trough PI concentration at W12, suggesting a possible drug-drug interaction of pravastatin on PI metabolism.
Bonnet
Fabrice
F
Service de Médecine Interne et Maladies Infectieuses, Hôpital Saint-André, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. fabrice.bonnet@chu-bordeaux.fr
Aurillac-Lavignolle
Valerie
V
Breilh
Dominique
D
Thiébaut
Rodolphe
R
Peuchant
Evelyne
E
Bernard
Noëlle
N
Lacoste
Denis
D
Dabis
François
F
Beylot
Jacques
J
Chêne
Geneviève
G
Morlat
Philippe
P
D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004347:Drug Interactions; D023381:Endpoint Determination; D005260:Female; D006678:HIV / Q000235:genetics / Q000302:isolation & purification*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D053419:Lipoproteins, IDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000008:administration & dosage* / Q000009:adverse effects; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D017320:HIV Protease Inhibitors; D053419:Lipoproteins, IDL; D012367:RNA, Viral; D017035:Pravastatin