d4T dose reduction improves lipoatrophy in Thai patients

Thai researchers report that d4T dose reduction appears to improve the appearance of lipoatrophy, whilst maintaining control of viral load in patients followed for a median of 18 months. The findings, presented this week at the Second International AIDS Society Conference on HIV Pathogenesis and Treatment in Paris, come from a cohort of 80 patients with lipoatrophy treated in Bangkok. The study was observational with no control group, but suggestive nevertheless.

All patients were receiving triple combination therapy, had undetectable viral load at the time of the dose reduction, and lipoatrophy. All were receiving d4T, 46 were receiving efavirenz, 24 a protease inhibitor and two abacavir. All but eight coupled d4T with 3TC; the remainder received ddI.

The d4T dose was reduced from 40mg to 30mg a day in 40 patients with body weight above 60kg (mean 67kg) and from 30mg to 20mg a day in 40 patients with body weight below 60 kg (mean 50kg).

At baseline, lipoatrophy was classified as severe in 17 cases, moderate in 41 cases and mild (slightly noticeable) in 12 cases.

After a median follow-up of 93 weeks, the researchers report that all patients have experienced improvement of lipoatrophy, with no cases of virologic rebound. Patients with mild lipoatrophy tended to have the fastest improvement, and in cases where improvement was slow to manifest, d4T dose was reduced to 50% of the standard dose for the body weight (i.e. 20 or 15mg minimum per day for >60 or

Overall body weight gains were greater in those with moderate or severe lipoatrophy (+2.2kg, range -4 to +19.9kg) (+1.1, range -6 to +6kg) than in those with milder lipoatrophy (+0.78kg, range -14 to +9.5kg). The weight loss in outliers was largely explained by weight loss due to dieting rather than treatment; for example, in the case of a patient who lost 14kg during the period of dose reduction, his baseline wight was around 100kg and his weight loss was planned, Dr Mattana Havanich of Bangkok's Chulalongkorn University told aidsmap.

Whilst switching from d4T is the preferred option in the developed world for dealing with lipoatrophy, this option does not automatically exist in countries such as Thailand, where d4T is one of the most affordable antiretrovirals, and substitutes are not easily found. The study authors recommend that d4T dose reduction should occur at the earliest sign of lipoatrophy.

These findings also imply that given the lack of virologic rebound observed in this population, d4T dose reduction should also be explored as a maintenance strategy after viremia is controlled.