NRTI-sparing regimens

There has been recent interest in whether dropping NRTIs altogether can deliver improvements in body fat distribution and halt lipoatrophy. ACTG 5125s was a metabolic sub-study of ACTG 5116, which randomised individuals with advanced HIV disease to switch from their existing stable therapy to either ritonavir-boosted lopinavir (Kaletra) with efavirenz (Sustiva) or efavirenz plus two NRTIs. The study recruited 62 participants.

At baseline the median total limb fat was 6kg, measured by DEXA scans. This increased by a median of 562g in those who switched to Kaletra / efavirenz, compared with a median loss of 246g in those who continued to receive NRTIs in their regimen (p = 0.097).

Among 46 patients who had been followed for a median of 104 weeks, those in the non-NRTI arm gained a median of 782g of limb fat, whilst those in the NRTI arm had lost a median of 900g of limb fat compared to baseline (p = 0.002).1

Another study, AACTG 5110, randomised 77 patients with viral loads below 500 copies/ml on d4T or AZT-containing regimens to switch this NRTI to abacavir (Ziagen), or to discontinue their current drug regimen and begin the NRTI-sparing combination of Kaletra and nevirapine (Viramune).

After 24 weeks, computed tomography (CT) scans showed that the 37 patients receiving the NRTI-sparing regimen had experienced a median increase of 8% in subcutaneous thigh fat (p = 0.06). This was compared to no change in the abacavir group.

Subcutaneous abdominal fat tissue increased in both groups (p < 0.05), but the effect was greater in the NRTI-sparing group (17 vs 9%, p = 0.008). Similarly, the ratio of visceral to total fat improved in both groups (p < 0.01), but the decrease was greater in the abacavir group (-9 vs 12%, p < 0.001).

The switch to the NRTI-sparing regimen was found to be immunologically safe, leading to a significant increase in CD4 cell count (8 cells/mm3, p = 0.03) after 24 weeks. Similar proportions of both groups also maintained undetectable viral loads (93 vs 92%).

AACTG 5110 is the first study to detect an improvement in lipoatrophy after only 24 weeks. However, the researchers warn that an 8% increase in limb fat from a very low baseline is modest, and unlikely to be detected by the patient.2

References

  1. Tebas P et al. Switch to a protease inhibitor containing/nucleoside reverse transcriptase inhibitor-sparing regimen increases appendicular fat and serum lipid levels without affecting glucose metabolism or bone mineral density. The results of a prospective randomised trial, ACTG 5125s, 2005
  2. Murphy R et al. Switching to thymidine analog-sparing or a nucleoside-sparing regimen improves lipoatrophy: 24-week results of a prospective randomized clinical trial, AACTG 5100. Twelfth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 45LB, 2005
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

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