SWITCHING

According to the results of the RAVE study, individuals with lipoatrophy who switch from a thymidine analogue to tenofovir (Viread) experience an improvement in limb fat and maintain virological suppression [2,3]. However, the best option for the management of patients without lipoatrophy with viral suppression on AZT is not yet established.

The objective of the SWEET study (Simplification With Easier Emtricitabine and Tenofovir), presented at the recent 11th European AIDS Conference (EACS) in Madrid (October 24-27, 2007), was to compare the efficacy, tolerability, and safety of switching from twice-daily 3TC/AZT (Combivir; lamivudine/zidovudine) to once-daily emtricitabine/tenofovir (Truvada), both in combination with once-daily efavirenz (Sustiva).

SWEET was a 48-week, prospective, open-label Phase III study conducted at 24 sites in the U.K. and Ireland. The study enrolled and evaluated 234 virologically suppressed patients with HIV RNA < 50 copies/mL for the last 2 consecutive tests and less than 400 copies/mL for more than 3 months.

Subjects were randomized 1:1 to continue with a regimen of Combivir plus efavirenz (n=117) or switch to a regimen of Truvada plus efavirenz (n=117). Baseline characteristics were well matched between study arms. The median prior duration of Combivir use was 36 months.

Results

° Of the 250 patients enrolled in the study, 234 received at least 1 dose of the study drug.

° Among patients who switched to Truvada plus efavirenz, 88% achieved a viral load less than 50 copies/mL at 48 weeks, compared with 85% of patients who continued with Combivir (intent-to-treat, missing = failure analysis; P=0.70).

° Median CD4 counts remained comparable between the study arms.

° Limb fat was measured using DEXA scans in a subset of 100 study participants, of whom 74 had both baseline and 48-week data available.

° In this sub-study, a median increase in limb fat of 0.21 kg was observed among patients who switched to Truvada and a median decrease of 0.14 kg was observed among patients who continued on Combivir (P=0.025).

° Differences in limb fat were more pronounced among patients who had less experience with AZT.

° At week 48, a median increase in hemoglobin of 0.5 g/dL was observed among Truvada patients and a median decrease of 0.1 g/dL was observed among those continuing on Combivir (P<0.001).

° 22% of patients who switched to Truvada (n=22) experienced an increase in hemoglobin greater than 1 g/dL at 48 weeks compared with 2% of continuing Combivir patients (n=2).

° Conversely, 9% of patients who remained on Combivir (n=8) experienced a reduction in hemoglobin greater than 1 g/dL, compared with 2% of patients who switched to Truvada (n=2).

° After 48 weeks, fasting total cholesterol fell by a median of 0.22 mmol/L (8.46 mg/dl) among Truvada patients, compared with a reduction of 0.06 mmol/L (2.30 mg/dl) among Combivir patients (P=0.23).

° Fasting triglycerides fell by a median of 0.17 mmol/L (15.45 mg/dl) among Truvada patients, but increased by 0.04 mmol/L (3.63 mg/dl) among those who continued treatment with Combivir (P=0.11).

° Renal (kidney) function remained within normal ranges in both treatment arms after 48 weeks of treatment, as measured by creatinine clearance (Cockroft-Gault) and estimated glomerular filtration rate (MDRD).

° Median creatinine increased by 3 ?mol/L (less than 0.01 mg/dL) among Truvada patients (P<0.001), but declined by 1 ?mol/L among patients in the Combivir group (P=0.57).

° 5% of patients taking Combivir and 3% taking Truvada discontinued the study drug due to adverse events.

° Adverse events included dizziness, insomnia, nausea, depression, and sleep disorders in the Truvada arm and angiosarcoma, pulmonary embolism, pulmonary hypertension, weight loss in the arms and legs, syncope, worsening of lipoatrophy, and depression in the Combivir arm.

Based on these findings, the study authors concluded that switching from Combivir to Truvada in persons receiving efavirenz:

° Maintains virological control of HIV;

° Improves hemoglobin levels;

° Preserves limb fat and leads to limb fat recovery.

Further, the authors stated that switching from Combivir to Truvada, even in the absence of clinical lipoatrophy, is of benefit to the patient. "This supports the recommendation for proactive switching within the EACS 2007 guidelines," they wrote.

Brighton and Sussex University Hospitals, UK; Chelsea and Westminster Hospital, London, UK; Gilead Sciences Ltd, Cambridge, UK.

Following are excerpts from a Gilead Sciences press announcement about the SWEET study:

11/06/07

Sources

M Fisher, G Moyle, R Ebrahimi, and others (SWEET Study Group). Switching from Combivir (CBV, AZT/3TC) to Truvada (TVD, TDF/FTC) Maintains Viral Suppression, Prevents and Reverses Limb Fat Loss, and Improves Biochemical Parameters: Results of a 48 Week Randomised Study. 11th European AIDS Conference (EACS). Madrid, Spain. October 24-27, 2007. Abstract PS5/7.

Gilead Sciences. Gilead Announces 48-week Data Evaluating Switching from Combivir to Truvada among Virologically-suppressed HIV Patients. Press Release. October 29, 2007.

References

1. European AIDS Clinical Society (EACS) Guidelines 2007. www.eacs.eu.

2. G Moyle and others. The RAVE study. AIDS 20: 2043-2050. 2006.

3. E Martinez and others. The BICOMBO study. 4th International AIDS Society conference. Sydney, Australia. July 22-25, 2007. Abstract WESS102. [LINK: