Pharmacokinetics and 48-week safety and efficacy of generic lopinavir/ritonavir in Thai HIV-infected patients.
BACKGROUND
Generic products reduce the costs of HIV treatment. Few generic second-line antiretroviral products are available. We assessed pharmacokinetics, safety and efficacy of generic lopinavir/ritonavir (LPV/r) produced by the Government Pharmaceutical Organization (GPO) of Thailand in Thai HIV-infected adults.


METHODS
This was a single-arm prospective study. Patients with plasma HIV-1 RNA<50 copies/ml for ≥24 weeks, who were protease inhibitor (PI)-naive or experienced, were eligible. Patients started generic LPV/r tablets, 400/100 mg twice daily. At week 4, therapeutic drug monitoring was performed and analysed by validated HPLC. In patients using Kaletra(®) (Abbott Laboratories, North Chicago, IL, USA) soft gel capsules (SGC) or generic LPV/r tablets produced by Mylan (Canonsburg, PA, USA; formerly Matrix, Hyderabad, India) prior to study entry, we compared the plasma minimum concentrations (Cmin) of the different formulations. Plasma HIV-1 RNA and safety were assessed until week 48.


RESULTS
A total of 70 patients (32 males) were enrolled. Mean (sd) age was 40.7 (7.9) years and mean (sd) body weight was 60.3 (9.0) kg. Before study entry, all patients were virologically suppressed using a PI-based regimen; 62 (88.6%) were using LPV/r (Kaletra(®) SGC n=22 and Mylan generic tablets n=40). Mean (sd) Cmin of GPO lopinavir and GPO ritonavir at week 4 were 7.1 (2.9) mg/l and 0.39 (0.21) mg/l, respectively, and not significantly different from the Cmin when taking Kaletra(®) SGC or Mylan generic tablets. After 48 weeks, 95.6% of patients maintained plasma HIV-1 RNA<50 copies/ml. Four grade 3 and no grade 4 adverse events were reported.


CONCLUSIONS
Generic LPV/r showed adequate levels, good tolerability and excellent 48-week efficacy.
The HIV Netherlands Australia Thailand Research Collaboration HIV-NAT, Bangkok, Thailand. reshmie.r@hivnat.org
Reshmie A
RA
Ramautarsing
Jasper
J
van der Lugt
Meena
M
Gorowara
Jiratchaya
J
Sophonphan
Jintanat
J
Ananworanich
Joep Ma
JM
Lange
David M
DM
Burger
Praphan
P
Phanuphak
Kiat
K
Ruxthungtham
Anchalee
A
Avihingsanon
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D061466:Lopinavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019438:Ritonavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013785:Thailand; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D004338:Drug Combinations; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D019438:Ritonavir