NRTI-sparing combination of ritonavir-boosted indinavir and efavirenz improves fat loss but worsens blood fat and sugar levels

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Patients who have failed an anti-HIV treatment regimen containing only nucleoside reverse transcriptase inhibitors (NRTIs) show modest improvements in fat loss from under the skin after switching to a combination of ritonavir (Norvir)-boosted indinavir (Crixivan) and efavirenz (Sustiva). However, these improvements come at the cost of deteriorations in blood fat, cholesterol and sugar levels, according to a small study published in the 1st September edition of The Journal of Infectious Diseases.

The investigators suggest that HIV treatment combinations using protease inhibitors that do not cause such serious metabolic changes such as atazanavir (Reyataz) or saquinavir (Invirase) may be more attractive options for the reversal of fat loss.

NRTIs, particularly d4T (stavudine, Zerit) and AZT (zidovudine, Retrovir) can cause loss of fat from under the skin or ‘lipoatrophy’. This is thought to be due to the drugs damaging the mitochondria within fat cells – the sub-cellular bodies that produce energy by breaking down food molecules.



A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

deoxyribonucleic acid (DNA)

The material in the nucleus of a cell where genetic information is stored.


Loss of body fat from specific areas of the body, especially from the face, arms, legs, and buttocks.


The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

To establish whether using a treatment regimen that does not include NRTIs can improve lipoatrophy, researchers from the HIV Netherlands Australia Thailand (HIV-NAT) Collaboration examined the responses of a group of 60 patients to an NRTI-sparing combination.

All of the patients had experienced failure of HIV treatment comprising two or three NRTIs. After having viral loads above 1000 copies/ml for a mean of 2.72 years, they began treatment with 800mg indinavir boosted with 100mg ritonavir twice a day and 600mg efavirenz once a day.

The patients had an excellent response to the new combination, with 87% having viral loads below 50 copies/ml after 48 weeks, and 69% after 96 weeks. CD4 cell counts increased by 103 cells/mm3 over the 96-week study.

The new treatment combination also allowed fat levels under the skin to improve slightly, as measured using scans of the trunk and leg. Overall, leg fat levels increased by a mean of 620g over the 96 weeks of the study (p = 0.003). This was paralleled by significant increases in fat under the skin in the leg (20 cm2, p 2, p 2, p = 0.01).

These changes were also mirrored by improvements in levels of mitochondria, measured as mitochondrial DNA levels. Over the first 48 weeks of the study, DNA levels increased by 109 copies/cell in fat cells (p = 0.02), and by 45 copies/cell in white blood cells (p = 0.01).

However, these improvements in fat loss were accompanied by deteriorations in blood fat, cholesterol and sugar levels. Total cholesterol levels increased from 4.5 to 7.4mmol/l (p

Although high-density lipoprotein (HDL or ‘good’) cholesterol increased from 0.9 to 1.3mmol/l (p

Triglyceride levels also increased from 1.7 to 4.5mmol/l (p

“We observed recovery of virological control, which, in the majority, was associated with clinically modest but statistically significant increases in peripheral and visceral fat as well as in mitochondrial nucleic acid content,” comment the investigators. “However, we also noted a substantial deterioration in overall metabolic profile, which might dispose patients to accelerated cardiovascular disease.”

Limitations of this study include the fact that it was not randomised and did not contain a control group, so it is difficult to determine whether these changes would have occurred without the new treatment regimen. In addition, it is impossible to tease apart the effects of the drugs themselves from the improvements in health caused by the control of HIV replication in the body.


Boyd MA et al. Changes in body composition and mitochondrial nucleic acid content in patients switched from failed nucleoside analogue therapy to ritonavir-boosted indinavir and efavirenz. J Infect Dis 194 (online edition), 2006.