Program Supplement [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

no prior antiretroviral therapy. All eligible infants receive
medication within 24 hours post-delivery and are advised about
the risk and benefits of breastfeeding(BF) and formula
feeding(FF). Infants are followed up for 6 months to ascertain their
HIV status. BF infants are followed up until 3 months post BF.
Results: A preliminary analysis was done on 781 infants who
were randomised between October 2000 and February 2002.
773(98,9%) infants were evaluable on day 1, 14(1.8%) infants
died with unknown HIV status and 192(25%) were lost to
follow up. 589 were evaluable at week 6. The proportion of FF
at 6 weeks was similar in both groups (82% NVP vs 83% ZDV).
NVP NVP ZDV ZDV

Median CD4
Viral Load
No.(%) CR pos at Day 1
Additional No. (%)PCR
pos at 6 weeks

383
383
381

438
18 400
23 (6.2%)

398
398
378

423
18 loo
22 (5.6%/o)

285 20 (7.0%) 304 33 (11.0%)

Factors affecting postnatal transmission were maternal
CD4<2oo(OR 3.1; 95% Cl 1.4; 7.0); maternal viral load <loo ooo(OR
0.40; 95% Cl 0.2; 0.86); and FF (OR 0.31; 95% Cl 0.14; 0.66).
Conclusion: Single dose NVP administered within 24 hours of
birth was no different to 6 weeks ZDV in reducing post-partum
MTCT.
Corresponding author: Gray, Glenda, Perinatal HIV Research
Unit, Chris Hani Baragwanath Hospital, PO Bertsham 2013,
South Africa, South Africa, Tel: [phone],
Fax: [phone], Email: [email protected]
LBOR14
Cytotoxic T lymphocyte responses in participants enrolled in
a phase I/11 canarypox (ALVAC)/ gpi2o B/E prime-boost HIV
vaccine trial in Thailand
de Souza, Mark1, Karnasuta, Chitraporn', Cox,
Josephine2, Nitayaphan, Sorachai', Pittisituttithum,
Punnee1, Brown, Arthur', Gurunathan, Sanjay2, Heyward,
William2, McNeil, John2, Birx, Deborah2
(Thailand; 2United States)
Background: The frequency of cytotoxic T lymphocyte (CTL)
responses was determined in HIV-seronegative recipients of
canarypox (ALVAC-vCP1521) expressing HIV subtype E Env and
B Gag/Pro and HIV recombinant bivalent gp120o (AIDSVAX~
B/E) as a boost.
Methods: The injection regimen was o, 1, 3 and 6 months. Five
subjects were initially enrolled in an open-label study to
assess the safety of ALVAC-vCP1521 (Aventis Pasteur, Lyon,
France). Volunteers in phase II were randomly assigned into
3 groups. Group I (N=3o) received placebo; Groups II (N=45)
and Ill (N=45) received ALVAC-vCP1521. Groups II and Ill
received a boost of 20oopg and 6oo00pg of AIDSVAX ~ B/E
(VaxGen, Inc., Brisbane, USA), respectively. CTL assays using
chromium release were conducted from baseline through
6 months following completion of immunisations. Freshly
isolated PBMC were stimulated in vitro with clade E and B
antigens and used as effectors with autologous B cells infected
with recombinant vaccinia viruses expressing clade E Env and
clade B Gag/Pol antigens as targets. CD8 specificity of a
positive CTL response was assessed.
Results: CTL responses conducted at baseline on 121
volunteers were uniformly negative. The cumulative prevalence
of HIV-specific CD8+ CTL activity in the ALVAC group was 24%

(22/93). No placebo recipients demonstrated CTL activity.
Initial positive CTL responses were observed as early as two
weeks following the second injection (3%), and as late as 6
months following the fourth-injection. The time-point with the
greatest CTL activity was 6 months following the last injection
(11%). CTL responses were observed to both Env and Gag/Pol
antigens. Cross-clade CTL responses to subtype E Gag antigen
were observed in 3/8 subjects tested.
Conclusion: ALVAC-vCP1521 is capable of inducing intra- and interclade CTL activity, thus supporting its use as a phase Ill vaccine
candidate in Thailand where two HIV subtypes are circulating.
Corresponding author: de Souza, Mark, Dept of Retrovirology,
AFRIMS, 315/6 Rajvithi Rd, Bangkok 10400, Thailand,
Tel: + 66 2 644 4888 ext 1515, Fax: + 66 2 644 4824,
Email: [email protected]
LBOR15I
Hepatic safety of nevirapine: results of the Boehringer
Ingelheim Viramune@ Hepatic Safety Project
Stern, Jerry, Lanes, Stephan, Love, James, Robinson,
Patrick, Imperiale, Michael, Mayers, Douglas (United States)
Background: The relationship between drug-induced
elevations in ALT/AST levels and subsequent significant clinical
liver injury is variable and often unpredictable. All ARV classes
have been associated with asymptomatic ALT/AST elevations
as well as severe, and at times life threatening, clinical liver
toxicity.
Methods: Boehringer Ingelheim (BI) has recently completed
the Viramune~ Hepatic Safety Project; its primary objective
was to identify risk factors for ARV hepatotoxicity. Data from
1,731 nevirapine (NVP)-treated patients and 1,912 control
patients who took part in BI-controlled clinical trials, as well as
814 NVP-treated patients in uncontrolled trials, were analyzed.
Several observational cohorts (N = 7894) were analyzed to
identify risk factors and will be discussed.
Results: Baseline elevations in ALT/AST >2.5xULN, often a
surrogate for HCV/HBV co-infection, and baseline CD4 cell
counts >350 cells/mm3 were risk factors for both symptomatic
and asymptomatic NVP-associated hepatotoxicity. Female
gender at higher CD4 counts may be a risk factor. Fulminant
hepatitis was rare in clinical trials and not observed in the
cohort studies. In controlled clinical trials there was no excess
hepatic mortality for NVP compared to controls. Clinical
(symptomatic) hepatotoxicity was an infrequent event (rate in
BI trials: 1-5%), and usually reversible with NVP
discontinuation. The majority of clinical hepatic events
occurred in the first 4 - 6 weeks of NVP therapy. Asymptomatic
ALT/AST> 5xULN occurred in 0.5-9% of patients in BI trials.
Conclusions: The majority of NVP-associated hepatic events
are asymptomatic and easily addressed by NVP interruption
until the ALT/AST return to baseline with subsequent
reintroduction of NVP on a case-by case-basis. In cohort
studies, NVP was not associated with a greater risk of clinical
hepatitis than other ARVs. Guidelines for managing NVPassociated hepatotoxicity will be presented.
Corresponding author: Stern, Jerry, Boehringer Ingelheim
Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877,
United States, Tel: [phone], Fax: +i 203 798 5433,
Email: [email protected]

24 Program Supplement