Programme Supplement [International Conference on AIDS (16th: 2006: Toronto, Canada)]

Late Breaker Abstracts

Medical College of Cornell University, Division of Outcomes and
Effectiveness Research, New York, United States, sWeill Medical
College of Cornell University, Division of International Medicine
and Infectious Diseases, New York, United States
Background: Two nucleoside reverse transcriptase inhibitors
(IJRTI) plus EFV is a widely used initial treatment regimen for HIVinfected individuals but concern remains about virologic potency
in subjects with high VL and/or low CD4. We compared VL and
CD4 responses based on pre-treatment VL and CD4 in subjects
receiving EFV with 2- or 3-NRTIs and assessed whether adding a
third NRTI improved responses in any subgroup.
Methods: A5095 randomized 765 treatment-naive subjects to 2- or
3-NRTIs+EFV with 3 years median follow-up. Pre-treatment VL and
CD4 were categorized into pre-determined subgroups (<30,000,
30,000-99,999, 100,000-299,999, >=300,000 copies/ml and
<50, 50-199, 200-349, 350-499, >=500 cells/mm3). VL and CD4
subgroup associations with risk of virologic failure (VF) (confirmed
VL>200 copies/ml) were analyzed using Cox proportional hazards
models; associations with CD4 increases from baseline at specific
weeks used normal linear models. Analyses were intent-to-treat.
Results: The risk of VF was not significantly different among VL and
CD4 subgroups and revealed no consistent trends Figure). The risk
of VF was not significantly different between subjects taking 2- vs.
3-NRTIs+EFV across VL (P=0.43) and CD4 subgroups (p=0.99).

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pts who initially had r-hGH Induction Tx were randomized to rhGH 2mg on alternate-days (Maintenance Tx) or PL. Patients who
initially had PL (BL to Wk 24) later received r-hGH 4mg daily (Wks
24-36). Primary endpoint was change in cross-sectional VAT area
on CT scan at L4-L5. Key secondary endpoints included change in
non-HDL cholesterol (C) and limb fat (LF) by DXA.
Results: 325 pts received at least 1 dose of study drug. BL:
age 44.8~7.1 years, 74.8% white; 85.4% male, HIV-1 RNA <400
copies/mL 81.7%, CD4+ count 499~282 cells/mm3. On Induction
Tx, change in VAT area at 12 wks was -32.6~37.9cm2 on r-hGH
and +0.5~34.5cm2 on PL (p<0.001). Compared to PL, pts on
GH Induction Tx had decreased LF, and non-HDL-C (p<=0.023).
During the Induction-Maintenance (BL to Wk 36), pts on r-hGH
Maintenance Tx sustained reductions in VAT (-26.6~43.9cm2) from
BL. Pts on PL maintenance sustained a small reduction in VAT (10.0~39cm2). By 36 wks there were no changes in limb fat from
BL in either group. At 36 wks, non-HDL-C remained decreased
on r-hGH Maintenance Tx, but not on placebo. There were no
unexpected AEs, no episodes of hyperglycemia or diabetes
requiring therapeutic intervention.
Conclusions: In HARS pts, r-hGH 4mg daily Induction Tx for 12
weeks significantly reduced VAT, trunk fat, and non-HDL-C, and rhGH
Maintenance Tx for 24 wks helped to sustain the clinical benefits.
THLBO213
Predictors of virologic failure and HIV drug resistance
among patients receiving fixed dose combination stavudine/
lamivudine/nevirapine in northern Tanzania
H.O. Ramadhani1, N.M. Thielman2, F. Gao3, J. Kirchherr3, R. Shah3,
K.Z. Landman2, E.M. Ndosi1, H.J. Shao1, S.C. Morpeth2, J. McNeiI2,
V.P. Maro4, J.F. Shaos, J.A. Bartlett2, J.A. Crump2. 1Kilimanjaro
Christian Medical Centre, KCMC-Duke University Collaboration,
Moshi, Tanzania, United Republic of, 2Duke University Medical
Center, Division of Infectious Diseases and International Health,
Durham, United States, 3Duke University Medical Center, Human
Vaccine Institute, Durham, United States, 4Kilimanjaro Christian
Medical Centre, Department of Medicine, Moshi, Tanzania, United
Republic of, 5Tumaini University, Kilimanjaro Christian Medical
College, Moshi, Tanzania, United Republic of
Background: To understand approaches to optimizing ART in
sub-Saharan Africa, we evaluated predictors of virologic failure
and drug resistance among patients who had received fixed dose
combination stavudine/lamivudine/nevirapine for >6 months at a
referral hospital in northern Tanzania.
Methods: Patients were administered a questionnaire and had
blood drawn from June-August 2005. Validated sociodemographic,
economic, adherence, access to care, and mental health questions
were asked. Virologic failure was defined as HIV RNA >400 copies/
mL. Factors associated with virologic failure were identified
by bivariable and multivariable logistic regression analyses.
HIV subtype and reverse transcriptase (RT) mutations were
ascertained.
Results: Among 150 patients, 94 (63%) were female, median
(range) age and duration on ART were 41 (19-69) years and 12
(6-27) months respectively, and 48 (32%) patients had virologic
failure. On multivariable analysis, virologic failure was associated
with proportion of months on ART that was self-funded >median
(AOR 4.2, p=0.002), and self-funded ART was linked with
maladherence (r=0.54, p<0.001). Disclosing HIV status to others
was protective (AOR 0.13, p=0.033). Of 27 samples with HIV RNA
concentration >1,000 copies/mL and for which HIV subtype could
be determined, 10 (37%) were subtype A, 7 (26%) C, and 10 (37%)
D. RT sequencing showed that 2 (7o) had 1 major resistance
mutation, 7 (26%b) had 2, and 6 (22%b) had _3. The presence of
1 mutation was associated with CD4 count <median at treatment
initiation (OR 4.8, p=0.009).
Conclusions: In this Tanzanian cohort, patients who paid for
ART were at risk for virologic failure mediated by maladherence.
Disclosure of HIV status, a likely marker of social coping, was
protective. Presence of resistance mutations was associated
with low CD4 count at ART initiation. Provision of free ART and
promotion of social coping may enhance virologic suppression in

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Similar CD4 increases over time were observed across all VL
and CD4 subgroups (median=277 cells/mm3). At 48, 96, and 144
weeks, CD4 increases were not significantly different for 2- vs.
3-NRTIs+EFV across VL subgroups (P>0.55) and across CD4
subgroups at weeks 48 and 144 (P>0.12).
Conclusions: In this randomized study of 2- or 3-NRTIs+EFV
pre-treatment VL and CD4 were not associated with treatment
outcome over a median of 3 years demonstrating the potency of
EFV-based regimens across a wide range of CD4 and VL. Adding a
third NRTI did not enhance responses in any subgroup.
THLBO212
Recombinant human growth hormone (r-hGH) to treat HIVassociated Adipose Redistribution Syndrome (HARS): 12 -week (Wk) induction and 24-wk maintenance therapy (Tx)
Grunfeld C.1, Thompson M.2, Brown S.J.3, Richmond G.4, Lee D.A.5,
Muurahainen N.6, Kotler D.P.7, and the Study 24380 Investigators
Group. 'UCSF-VA Med. Center, Div. of Endocrinology, San Francisco,
United States, 2AIDS Research Consortium, Atlanta, Georgia,
United States, 3AIDS Research Alliance, W. Hollywood, United
States, 4Richmond Clinic, Fort Lauderdale, United States, sUCSD,
Antiviral Research Center, San Diego, United States, 6Serono,
Inc., Clinical Development, Rockland, United States, 7Columbia/St
Lukes-Roosevelt, GI Immunology, New York, United States
Background: Excess accumulation of truncal fat, including
visceral adipose tissue (VAT), in HIV-infected persons (HARS) is
associated with risks to health and psychosocial well-being. No
therapies are currently approved to treat HARS.
Methods: Randomized, double-blind, placebo-controlled, multicenter trial, comparing effects of r hGH (Serostim~) to placebo
(PL) in reducing VAT in HARS. Induction Therapy (Tx) was r hGH
4mg daily vs. PL from baseline to Wk 12. From Wks 12 to 36,

XVI INTERNATIONAL AIDS CONFERENCE * 13-18 AUGUST 2006 * TORONTO CANADA * PROGRAMME SUPPLEMENT