d4T (stavudine) among young children in sub-Saharan Africa remains the greatest
risk factor for lipodystrophy syndrome (that includes lipoatrophy and
lipohypertrophy) for a significant proportion of children, urgently highlighting
the need for early detection of abnormal body fat changes, researchers
reported at a poster session at the 19th
Conference on Retroviruses and Opportunistic Infections in Seattle this week.
Treatment with d4T is a well-established risk factor for the loss of subcutaneous body fat
(lipoatrophy) in adults after starting antiretroviral therapy. Lipoatrophy is
much less frequent in people who receive tenofovir-based treatment and for this
reason the World Health Organization has urged national treatment programmes to
drop d4T and move to tenofovir- or AZT-based treatment wherever affordable.
exist on the extent of abnormal body fat changes among HIV-positive
children in sub-Saharan Africa where d4T is in common use. Among the estimated
2.3 million HIV-positive children, from 2008 to 2009, approximately 88% were on
an ART regimen containing d4T.
Innes of Tygerberg Children’s Hospital, Cape Town, presented findings from a
cross-sectional study of the first 100 of 300 children aged 3 to 12 on ART
along with 34 controls attending a family HIV clinic. Dr Innes and colleagues
looked at the extent, accurate diagnosis and risk factors for lipoatrophy in
pre-pubertal African children.
An expert HIV
paediatrician visually graded for lipoatrophy. Anthropometric measurements of
trunk and limb skinfold thickness and circumference measurements were done.
Dual-energy X-ray absorptiometry (DEXA) scans were performed on 42 patients and the
34 controls. Length of time on ART was noted.
(36%, CI: 27%-45%) of the children had clinical lipoatrophy.
distribution according to DEXA and anthropometrics was compared among children
who were HIV-negative, HIV-positive with lipoatrophy and HIV-positive without
lipoatrophy adjusting for age and sex. These objective measures confirmed the
clinical assessment of visually obvious lipoatrophy.
DEXA total extremity fat was 2.7 kg in HIV-negative children, 1.7 kg in HIV-positive
children with lipoatrophy and 2.3 kg in HIV-positive children without lipoatrophy,
a statistically significant difference (p = 0.0001).
anthropometrics showed biceps skinfold thickness was 5.5, 4.2 and 5.3 in
HIV-negative children, HIV-positive children with lipoatrophy and HIV-positive children without
lipoatrophy, respectively (p<0.0001).
were graded as having lipoatrophy were no sicker and did not start ART at a
different time from those without lipoatrophy.
risk factor for clinical lipoatrophy, controlling for age, sex and CD4
percentage was the cumulative length of time on d4T (p = 0.0008). The odds ratio
nearly doubled for each additional year of accumulated d4T exposure (OR = 1.9,
95% CI: 1.3-2.9, p = 0.002).
concluded that these findings show that diagnosis by visual grading in
resource-limited settings where precise anthropometry and DEXA are routinely not
available is a reliable alternative.
presentation, he stressed the stigmatising nature of lipoatrophy, uniquely relevant
to sub-Saharan Africa. The effect can be life-threatening since community acceptance is critical to
accessing communally-held resources including healthcare.
Shiaul, on behalf of the NEVEREST team, presented findings comparing the
metabolic profiles and fat distribution of HIV-positive South African children
with and without clinical lipodystrophy (LD) who began ART before the age of
One hundred and fifty-six perinatally HIV-infected children who had achieved viral suppression on lopinavir/ritonavir (LPV/r)
and had been randomised to remain on LPV/r or switched to nevirapine with d4T
and 3TC (lamivudine) as a backbone were evaluated for visible signs of
assessed the children. The children were classified as follows: lipodystrophy,
possible lipodystrophy or no lipodystrophy if two or more, one or none,
respectively, of the following were present:
sunken cheeks, temporal wasting, skinny limbs, wasting of buttocks.
increased abdominal girth, dorsal cervical or breast enlargement.
bio-impedance analysis, viral load, CD4, fasting total cholesterol, HDL, LDL
and triglycerides were measured. Estimates of measures of regional fat
including trunk-extremity skinfold ratios were done. The outcomes were then
compared with the clinician-defined lipodystrophy groups.
The mean age
of the children was 5.1 ±0.8 years with ART started at a mean age of 10.7 ±6.0
months. Thirteen (8.4%) were classified as lipodystrophy cases; 18 (11.5%) as possible
lipodystrophy; and 125 (80.1%) as no lipodystrophy.
three groups no differences were seen in age, gender, age when
starting ART, time on ART, weight, height, body mass index or proportion with a
viral load under 50 copies/ml.
proportion of children with lipodystrophy who remained on LPV/r-based ART or
switched to nevirapine-based ART were similar, 7.1% compared to 9.9%, p = 0.51,
lipodystrophy had less body fat compared to children without lipodystrophy
according to mean cumulative skinfold thickness (34.1 ±5.7 compared to 42.0 ±11.1 mm, p = 0.016).
age, sex and total fat, a similar pattern of differences in arm, trunk and leg
fat between those with and without lipodystrophy was seen.
proportion of children with triglycerides greater than 150 mg/dL was
significantly higher for children with lipodystrophy and possible LD than in
those without lipodystrophy (23.1, 22.2 and 4.8%, respectively).
concluded that a substantial proportion of children who start d4T-containing
ART regimens before two years of age have clinical signs of lipodystrophy.
As with Dr
Innes’ findings, use of objective anthropometry confirmed the clinical
In many resource-poor
settings, d4T is part of a fixed-dose combination. Dr Innes stressed that little
is known about the long-term effects of d4T on children. A lot of work remains
to be done in learning how to care for these children going forward, he
constraints and limited alternatives mean that it is likely d4T will remain
part of first-line ART in resource-poor settings for a considerable time to
from the audience highlighted many unanswered concerns including knowing the
best time to switch. While it was suggested that lipodystrophy was
irreversible, some participants questioned whether this was in fact true. An
ongoing trial looking at switching from d4T to abacavir may be able to shed
light on the reversibility of its effects on body fat changes. Other
participants raised the issue of a dose effect on toxicity; a lower dose of d4T
may reduce the metabolic consequences and be effective.
found a visual grading scale is reliable and easy to use to catch changes in
body fat at the earliest stage. This is critical given the high prevalence of
lipodystrophy in young children and its stigmatising effects in sub-Saharan