To the Editors:
Atazanavir (ATV) is the first once-daily protease inhibitor (PI) approved with a recommended dose of 400 or 300 mg and boosted with ritonavir (RTV). Coadministered with RTV, the CYP3A4 isoenzyme inhibitor markedly increases the ATV blood level. ATV/RTV-300/100 results in a 4-fold increase in the trough concentration compared with a dose of 400 mg once daily.1
ATV has the lowest pill burden and best favorable effects on the lipid profile compared with other PIs; however, ATV has a higher cost compared with other PIs. If a lower dose of ATV/RTV could be used as safely as a low-dose of indinavir/RTV-400/100 twice daily in Thai patients,2 it would be preferable for more resource-limited settings.
We retrospectively reviewed HIV-infected adult patients who were on antiretroviral treatment with a viral load <50 copies/mL and had changed their regimen to ATV/RTV-200/100 mg once daily as boosted PI plus 2 nucleoside reverse transcriptase inhibitors or nonnucleoside reverse transcriptase inhibitor. Their CD4, HIV RNA, and fasting lipid profiles were monitored every 3-6 months. Some of the patients had blood obtained for ATV trough levels.
There were 14 HIV-infected patients in this cohort averaging (SD) 47 years of age (±11.4). The demographic and clinical data are presented in Table 1. Most of the patients were female (57%) with a median body weight of 53.5 kg (range = 46-74 kg). The mean (SD) baseline CD4, before switching, was 299.5 (±152.5) cells/mm3. The respective median (range) of baseline fasting total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was 213 (128-307), 224 (85-497), 121 (33-197), and 42 (29-94) mg/dL. The median duration of follow-up was 68.1 (range = 12-165) weeks.
During the follow-up period, all the patients had viral suppression (<50 copies/mL). The mean CD4 (SD) count was significantly increased from 299.5 (±152.5) to 420.1 (±135.1) cells/mm3 (P = 0.001). The respective median (range) change in fasting TC, triglyceride, LDL-C, and HDL-C was −7 (−98 to 59), −46 (−226 to 87), −8 (−79 to 72), and 0 (−30 to 26) mg/dL; however, the changes were not statistically significant. All the patients tolerated the treatment very well and none discontinued the medication due to any adverse reaction. All 5 cases had their ATV trough levels checked and had levels >150 ng/mL, which is the minimum target trough level required by the Department of Health and Human Service guidelines.3
In this cohort study, we demonstrated the long-term efficacy of low-dose ATV/RTV-200/100 once daily as part of an antiretroviral therapy regimen. All the patients achieved undetectable HIV RNA (<50 copies/mL) during a median follow-up of 68 weeks. (Five of the patients had been followed up for as long as 2 years.) The finding was confirmed by adequate trough levels in 5 cases for whom blood had been obtained. This might be explained by the relatively low body weight in our cohort (median = 53.5 kg); however, patient no. 3 had an adequate ATV level even though he was taking ATV with efavirenz, which usually results in decreased ATV blood levels.4 These results provide some evidence that this regimen is adequate in HIV-infected patients in Thailand. It had a minimal effect on lipid profiles, and none of the patients discontinued the medication due to any adverse reaction.
In conclusion, the use of ATV/RTV-200/100 mg once daily, as a boosted PI, was effective in HIV-infected Thai patients. This combination markedly lowered the cost of treatment. In addition, this regimen is safe, well tolerated, and has a low pill burden compared with other PIs and therefore should be considered as a boosted PI regimen in resource-limited settings. Notwithstanding, a full pharmacokinetic study and a large clinical trial should be conducted to confirm our findings.
The authors thank the HIV-NAT for performing the ATV trough concentration, Faculty of Medicine for its support, and Mr. Bryan Roderick Hamman for assistance with the English language presentation of the manuscript.
Ploenchan Chetchotisakd, MD
Siriluck Anunnatsiri, MD, MPH, MCTM
Department of Medicine
Faculty of Medicine
Khon Kaen University
Khon Kaen, Thailand
1. Agarwala S, Russo R, Mummaneni V, et al. Steady-state pharmacokinetic (PK) interaction study of atazanavir (ATV) with ritonavir (RTV) in healthy subjects. In: Abstract of the Forty-Second Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA
. Abstract H-1716. Washington, DC: American Society for Microbiology; 2002:274.
2. Mootsikapun P, Chetchotisakd P, Anunnatsiri S, et al. Efficacy and safety of indinavir/ritonavir 400/100 mg twice daily plus two nucleoside analogues in treatment-naive HIV-1-infected patients with CD4+ T-cell counts <200 cells/mm3
: 96-week outcomes. Antivir Ther
3. AIDSinfo. Guideline for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents. Available at: http://AIDSinfo.nih.gov
. Accessed February 23, 2008. Rockville, MD: U.S. Department of Health and Human Services; 2007.
4. Poirier JM, Guiard-Schmid JB, Meynard JL, et al. Critical drug interaction between ritonavir-boosted atazanavir regimen and non-nucleoside reverse transcriptase inhibitors. AIDS