Update From Retrovirus on Switching Studies
     Reported by Jules Levin & Gilbert Kaufman, MD, Univ Hosp Basel, Switzerland

Here are selected reports from the Conference that are of interest...

Does Switching Therapy Improve Body Changes & Lab Abnormalities?
An important question is whether a substitution of a non-nucleoside analogue RTI for a PI can revert lipodystrophy and PI associated metabolic complications. Metabolic complications are improvable but so far there still are no consistent significant improvements seen in body changes.

The findings of this study suggest a switch to EFV from PI slows fat depletion compared to remaing on a PI but people on EFV still continued to experience fat depletion.
(abstract 669)
Martinez and colleagues studied the substitution of efavirenz for a PI in HIV-1-infected adults treated with PI-containing HAART for at least the previous 6 months with <200 copies/ml and body fat accumulation and/or depletion. Patients were randomized to continue PIs or to receive efavirenz. 93 patients (46 efavirenz, 47 PI) were included. At 12 months, patients on efavirenz had significant decreases in body mass index, severity scores of lipodystrophy of abdomen, buttocks and extremities. Moreover, significant increases in insulin sensitivity and HDL-cholesterol were observed. In contrast, patients on PI had higher increases of intra-abdominal fat thickness (accumulation of fat in the abdomen) and higher decreases of subcutaneous fat in the extremities (fat depletion), although those assigned to efavirenz also had progressive decreases of subcutaneous fat. Authors said there was good correlation between patient perception & objective sonograph measures of body changes. The authors conclude that the replacement of a PI by efavirenz was safe and appeared to slow the evolution of body fat changes.

This study reports less lipoatrophy in the Abacavir Regimen than in the Nelfinavir regimen. Also, improved response of triglycerides & cholesterol in Abacavir regimen vs nelfinavir regimen.
(abstract 670)
Matheron and colleagues presented on behalf of the CNAF3007 Study Group a inverstigation which compared metabolic and morphologic abnormalities related to lipodystrophy in 195 HIV-1-infected naïve adults receiving combivir + abacavir (COM/ABC) versus combivir/nelfinavir (COM/NFV) for 48 weeks. Baseline metabolic values were normal in both groups & comparable comparing the two groups. At week 48, median increases in total cholesterol were significantly lower in the COM/ABC than in COM/NFV group. There was a tendency for lower increases in triglyceride levels in the COM/ABC group. Moreover, median increases in glucose levels were identical in both groups. Changes from baseline of morphologic measures and weight did not differ between groups. 6% of patients (6/96) in COM/ABC group experienced new clinical signs compatible with lipodystrophy versus 12% (11/92) in COM/NFV group. Authors reported in program abstract that of 23 new lipodystrophy manifestations, there were 1 vs 5 cases of lipoathrophy and 1 vs 4 cases of venous abnormalities reported in the ABC vs NFV groups, respectively. The authors concluded that triglycerides, total cholesterol and glucose levels increased slightly in both groups, whereas lipoatrophy of inferior limbs and venous abnormalities were observed slightly more frequently in subjects on the PI-containing regimen.

Switch to Abacavir in This Study Showed Improved Lipids in 3 Months Sustained for 12 Months Follow-Up
(abstract 672)
Walli and colleagues did a pilot study in 31 patients with HAART-associated metabolic disturbances. 16 patients were switched from a PI to abacavir (ABC group) and 15 patients continued on PI. Fasting lipid were taken at baseline and months 3, 6, 9 and 12, and followed for 1 year. Median insulin sensitivity markedly increased in the abacavir group and decreased in the PI group. Median triglycerides markedly decreased in the abacavir group. Similarly, total cholesterol decreased in the abacavir group. In contrast, there was only little change in both triglycerides and cholesterol in the PI group. The authors concluded that switching from a PI to abacavir results in an improvement of insulin sensitivity and a decrease in both total cholesterol and triglycerides in the majority of patients with PI-associated metabolic disturbances. This effect is seen as early as 3 months after switching and is sustained over 12 months.

These reports suggest that metabolic complications can be more easily reversed than body shape changes. The full extent of reversal of these adverse events that can be achieved by a switch to a non-nucleoside analogue RTI needs certainly a longer follow up.

Nevirapine May Offer Less Risk (Atlantic Study Analysis: NVP vs 3TC Triple Nukes vs IDV regimens)
Van Der Valk and colleagues determined lipoprotein profiles in prospectively collected (fasting not mandated) plasma samples at baseline and at 24 weeks in the Atlantic study. Patients were randomly assigned to treatment with d4T+ddI plus either nevirapine (NVP), indinavir (IDV), or 3TC. A profile including a 33% increase in HDL-c (good cholesterol), a decrease in the total cholesterol/ HDL-C ratio, an increase in HDL size, as well as in Apo AI and Lp AI levels, was observed in patients on NVP at 24 weeks (n=31), but not in patients on IDV or 3TC. Other studies have consistently shown improvements in key lab tests of lipid abnormalities after switching to NVP regimens from PI regimens.

The authors conclude that a regimen of d4T/ddI plus NVP, but not IDV or 3TC, results in a lipid profile which is associated with a sharp reduction in coronary arterial disease risk in other settings.