The results of the D:A:D study, recently published in the New England Journal of Medicine, suggested that patients with HIV infection are more likely to have cardiovascular events than HIV-negative subjects, and that the increased risk is associated with HAART.

The Italian group of Maggi, et al. did a cross-sectional study to look at ultrasonographic differences in carotid dopplers among patients receiving protease inhibitor (PI)-based therapy, NNRTI-based therapy or double nucleosides. Previous studies have shown cross-sectional associations between common-carotid-artery intima-media thickness (IMT) and cardiovascular risk factors, the prevalence of cardiovascular disease, and atherosclerosis.

During last year's Retrovirus conference, two very similar studies were presented: one from the ACTG (Judith Currier) and one from the UCSF group. In the ACTG cross-sectional study, three types of participants enrolled (HIV-infected subjects with continuous use of PI therapy for >2 years; HIV-infected subjects without prior PI use; and HIV-uninfected subjects). The subjects were matched for age, sex, race/ethnicity, smoking status, blood pressure and menopausal status. No difference was found among the three groups in intima thickness. This was a surprise because we were all expecting that PIs would be bad. The UCSF study showed -- in its longitudinal part -- that patients on PIs had more rapid progression of the vascular lesions, but the study was somewhat small and was plagued with methodological problems.

This presentation seemed to be more supportive of the UCSF study than the ACTG study. PIs were worse than NNRTIs in all measurements: of the 55 patients receiving PI therapy, a little more than half had lesions in the vascular wall versus only 15% in the other two groups. This is good news for the NNRTI group, but we all know now that NNRTIs are more lipid- (and probably vascular-) friendly than PIs, especially boosted PIs. The study also showed that classic cardiovascular risk factors such as smoking were more prevalent in the patients with lesions. Not very many details were given (because of the relatively small sample size) about the specific PIs, duration of therapy and relationship with vascular lesions. Many studies have taught us that not all PIs are created equal in this regard. In fact, ACTG 5005, presented during this meeting by Michael Dube (Abstract 74), showed that the PI nelfinavir (NFV, Viracept) elevates lipids in a similar way to the NNRTI efavirenz (EFV, Sustiva). In other studies, we have also learned that not all NNRTIs are equal either (in the 2NN study, for example, we learned that nevirapine is the most lipid-friendly of the NNRTI class members).

The main limitation of this Italian study is its cross-sectional nature, and because of that, in reality it does not add that much to what we already knew.

As usual, we will need more longitudinal studies to better understand what is happening.

Footnotes

1. J. Currier, M. Kendall, K. Henry et al. Carotid Intima-Media Thickness in HIV-Infected and Uninfected Adults: ACTG 5078. Presented at: 10th Conference on Retroviruses and Opportunistic Infections; February 10-14, 2003; Boston, Mass. Abstract 131.

2. P. Hsue, J. Lo, A. Franklin et al. Increased Atherosclerotic Progression in Patients With HIV: The Role of Traditional and Immunologic Risk Factors. Presented at: 10th Conference on Retroviruses and Opportunistic Infections; February 10-14, 2003; Boston, Mass. Abstract 139LB.

3. M. Dubé, R. Zackin, R. Parker, Y. Yang, S. Grinspoon, P. Tebas, G. Robbins, R. Shafer, S. Snyder, K. Mulligan, and Adult AIDS Clinical Trials Group. Prospective Study of Glucose and Lipid Metabolism in Antiretroviral-Naive Subjects Randomized to Receive Nelfinavir, Efavirenz, or Both Combined With Zidovudine + Lamivudine (ZDV + 3TC) or Didanosine + Stavudine: A5005s, a Substudy of ACTG 384. Presented at: 11th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2003; San Francisco, Calif. Abstract 74.

Reference

Abstract: A Color Doppler Ultrasonographic Comparative Study Between Patients Treated With PI-Including Regimens vs. NNRTI-Including Regimens (Prevaleat Study) (Poster 735)
Authored by: P. Maggi, G. Epifani, F. Perilli, A. Lillo, A. Favia, N. Ladisa, A. Chirianni, M. Gargiulo, S. Ferraro, R. Maserati, G. Ravasi, A. Martignoni, B. Grisorio, S. Ferrara, C. Pellegrino, Prevaleat Study (Premature Vascular Lesions and Antiretroviral Therapy)
Affiliations: Univ. of Bari, Italy; Cotugno Hosp., Naples, Italy; Univ. of Pavia, Italy; Gen. Hosp., Foggia, Italy