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Metabolic Changes in Protease Inhibitor-Naive Patients Treated for 1 Year With Lopinavir/Ritonavir

Galindo, Maria José MD, PhD*; Verdejo, José MD; Gonzalez-Muñoz, Miguel PhD; Ferrer, Ana MD*; Polo, Rosa MD, PhD§

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 15th, 2008 - Volume 48 - Issue 5 - p 628-629
doi: 10.1097/QAI.0b013e31816d9cf8
Letters to the Editor

*Infectious Diseases Department Hospital Clinico Universitario Valencia, Spain; †Internal Medicine Service Hospital Madrid Torrelodones Madrid, Spain; ‡Department of Immunology Hospital Carlos III Madrid, Spain; §National Plan of AIDS Madrid, Spain

To the Editor:

Certain metabolic complications are common in HIV-positive patients treated with antiretroviral therapy. These alterations, especially hypercholesterolemia, could increase the cardiovascular risk (CVR), as measured by the Framingham risk score (FRS). Lopinavir coformulated with ritonavir (LPV/r) is an effective and potent protease inhibitor (PI) with a high genetic barrier, which can produce hypercholesterolemia, hypertriglyceridemia, and insulin resistance.1

To assess the CVR, using the FRS in patients treated with LPV/r, we designed a prospective, open-label, 1-arm study lasting 12 months. Seventy-three (71.2% male) consecutive PI-naive patients were included in the study and received treatment with LPV/r combining a nucleoside/nucleotide backbone.

Exclusion criteria were PI-experienced, pregnant, or breast-feeding patients; those receiving concomitant treatments with investigational drugs or with agents that might have potential major interactions with LPV/r; and, finally, patients younger than 18 years of age. The inclusion period was from January 2001 to January 2002.

The route of HIV transmission among the 73 included patients was heterosexual intercourse in 39.4%, injection drug abuse in 38.0%, homosexual intercourse in 19.7%, vertical transmission in 1.4%, and others (unknown) in 1.4%. The concurrent antiretroviral therapy was lamivudine in 41.8%, zidovudine in 24.3%, stavudine (d4T) in 11.4%, tenofovir in 11.4%, didanosine in 8.1%, and abacavir in 2.7%.

Patients were evaluated clinical and analytically at baseline and every 3 months thereafter. Patients had the following baseline characteristics: duration of HIV infection for 62.9 ± 65.7 months, CD4 T-lymphocyte count of 263 ± 263 cells/μL, CD4 T-lymphocyte percentage of 14.2 ± 9.6%, and plasma HIV-1 RNA level of 415,512 ± 960,152 copies/mL. Initially, the average CVR factor was 1.7 ± 0.9. The number of risk factors per patient was 0 CVR in 5 patients (6.8%), 1 in 24 patients (32.9%), 2 in 32 patients (53.8%), 3 in 11 patients (15.1%), 4 in 0 patients, and 5 in 1 patient (1.4%). The salient CVR was smoking (72.6%). Other common CVRs were age (men older than 45 years of age) in 15.1% of patients and hypertension in 11.1% of patients. The family heart disease history showed that 2.7% of the fathers of patients had ischemic heart disease, and the figure was 4.1% in the case of the mothers of patients. None of the patients had diabetes. Taking into account all CVRs, the FRS was initially 4.4 ± 6.9.

At baseline, the levels of cholesterol, high-density lipoprotein (HDL) cholesterol (HDLc), low-density lipoprotein (LPL) cholesterol (LDLc), triglycerides (TGs), and glucose were 165.0 ± 49.4 mg/dL, 35.5 ± 13.6 mg/dL, 99.2 ± 41.6 mg/dL, 160.9 ± 89.0 mg/dL, and 93.1 ± 12.7 mg/dL, respectively. The immunologic, virologic, and metabolic data at the end of the study (12 months) are shown in Table 1. We found a significant increase in total cholesterol, HDLc, and LDLc. TGs also showed an increase that was not significant. No cases of diabetes were diagnosed. LPV/r was discontinued in 19 cases: 12 of them because of side effects (diarrhea and/or digestive alterations in 10 cases) and 5 because of loss to follow-up. Twenty-eight patients were treated for dyslipemia, of whom 25 were treated only with diet and 3 were treated with diet and specific lipid-lowering drugs. Statins were used in 3 to achieve the National Cholesterol Education Project (NCEP) Adult Treatment Panel III (ATPIII) goals. We found no significant increase in the CVR, using the FRS. Accordingly at baseline, the CVR was 4.4; however, after 12 months on the LPV/r-based regimen, the CVR stood at 6.3. This increase was not significant (P = 0.059).



We know that d4T can induce dyslipemia.2 To assess if the lipid profile could change when the backbone included d4T in an LPV/r-based regimen, the patients were divided into 2 groups: a d4T group and a non-d4T group. Twelve and 45 patients, respectively, completed the treatment for 12 months in each group. No significant difference was found between the 2 groups in the lipid profile.

In conclusion, correct management of metabolic complications permits the use of LPV/r without a significant increase in CVR. In fact, the use of LPV/r is recommended in a PI-based regimen in different guidelines for treating antiretroviral-naive patients.3-5 Although a PI-based regimen can produce dyslipemia, correct management of modifiable CVR factors, such as a smoking habit, hypertension, or diabetes, is equally essential. In this series, more than 70% of patients were smokers.

Maria José Galindo, MD, PhD*

José Verdejo, MD†

Miguel Gonzalez-Muñoz, PhD‡

Ana Ferrer, MD*

Rosa Polo, MD, PhD§

*Infectious Diseases Department Hospital Clinico Universitario Valencia, Spain

†Internal Medicine Service Hospital Madrid Torrelodones Madrid, Spain

‡Department of Immunology Hospital Carlos III Madrid, Spain

§National Plan of AIDS Madrid, Spain

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© 2008 Lippincott Williams & Wilkins, Inc.