A Decade of the Thai Red Cross AIDS Research Centre

The Vanguard and ESPRIT studies
The immunomodulator, recombinant interleukin-2
(IL-2), was tested in a series of dose-ranging "Vanguard"
protocols in Thailand, Argentina, United Kingdom and USA.
The results of the Thai Vanguard study were published in AIDS
in 2000. Participants were randomised to receive ARV plus
IL-2 or ARV alone. The phase Ill ESPRIT study, with sponsorship
from the NIH, is currently enrolling 4,000 patients world-wide,
with 300 participants in Thailand. This clinical endpoint study
is scheduled to run for 5 years. HIV-NAT is the National Trials
Co-ordinating Centre (NTCC) for five trial sites in Thailand;
Chiangrai and Khonkaen in the north of Thailand, Chonburi in
the south and two sites in Bangkok (Chulalongkorn and Siriraj
Hospitals). The NTCC in each country is responsible for site
training and monitoring, data collection and transmission to
the NIH, drug importation, storage and distribution and the
financial management of the study.
HIV-NAT 005
A randomised, open-label, comparative study to
evaluate the efficacy and tolerability of indinavir/ritonavir (800
mg/100 mg bid) versus indinavir 800 mg tid as part of
combination ARV therapy with AZT/3TC in a nucleoside pretreated Thai population. 104 patients enrolled in 1999 and 96
continue in the extension protocol. Results of the clinical and
pharmacokinetic studies were presented at the 8th Conference
on Retroviruses and Opportunistic Infections in Chicago, 2001.
HIV-NAT 007
The first paediatric study conducted at HIV-NAT
assessed the safety, tolerability and pharmacokinetics of
nelfinavir co-administered with two nucleosides to HIV-exposed
neonates. Three cohorts, each consisting of 12 infants born to
HIV-infected mothers, were enrolled in this open label, doseescalating study during 1999. All mothers received zidovudine
prophylaxis during pregnancy and delivery according to Thai
Ministry of Public Health guidelines. To date, all the infants
remain HIV negative. Manuscript for publication is in preparation.
2NN Study
With 200 patients enrolled, HIV-NAT is the largest study
site in the international study of 1200 patients being conducted
at 18 centres world-wide. Participants are randomised to receive
nevirapine or efavirenz or both in combination with d4T and
3TC
HIV-NAT 009
An open label, single arm, non-randomised study to
evaluate the efficacy, safety and tolerability of indinavir 800mg
BID plus ritonavir 100mg BID, in combination with efavirenz
600mg OD, in HIV-1 infected patients who are pre-treated with
and have failed combination nucleoside reverse transcription
therapy.
T20 pharmacokinetic interaction studies
The three studies in this series will investigate the
pharmacokinetic interactions between T20, rifampicin, ritonavir
and the combination of saquinavir/ritonavir.
T-20 roll-over safety study.
This protocol is will collect long-term safety data on
T20 and provide continuing T-20 for patients who complete the
pharmacokinetic studies. The study sponsor will provide
funding to allow all patients access to combination antiretroviral
therapy for a period of 2 years post study. A HIV-NAT led protocol
is in development to combine the safety protocol with
combination antiretroviral therapy to produce a new 2 year
randomised trial.

HIV-NAT 010
The first pediatric antiretroviral therapy trial designed
to evaluate the question of when to start therapy. This
14 THE THAI RED CROSS AIDS RESEARCH CENTRE 2002

randomised, open label, comparative study will evaluate the
efficacy, safety, and cost of immediate versus deferred therapy
with zidovudine/lamivudine/nevirapine in HIV-infected Thai
children with moderate immunodeficiency. Enrollment began
in November 2001, initially with 40 children with plans to expand
to the full study of 260 children when more funding becomes
available.
Staccato
A multi-national (Switzerland-Australia-Thailand) trial to
evaluate the strategy of structured treatment interruption of
antiretroviral therapy. This is an open label, randomised study
to evaluate the efficacy, safety, and tolerability of continuous
daily boosted Saquinavir Hard Gel Capsule/d4T/ddl versus
structured treatment interruption (STI) of the same therapy either
given for one week on therapy alternating with one week off
therapy (Week on/Week off treatment) or given depending on
CD4+ T cell counts (CD4-guided treatment). Four hundred
Thai HIV-1 infected population will be enrolled as part of the
multi-national cohort of 600 patients.
Other studies
In progress are two registrational studies, one of a
new formulation of a nucleoside reverse transcriptase inhibitor
(NRTI) and the other of a new once daily protease inhibitor,
where data will be used by the pharmaceutical sponsor to
register these drugs by the United States FDA. A total of 50
patients are enrolled in these two studies. The effect of anabolic
steroids on HIV-wasting and ARV-associated osteoporosis is
being studied in 24 Thai patients enrolled in a multi-centre
study.
BASIC SCIENCE PROGRAMME
The HIV-NAT research laboratory is staffed by a
manager, seven medical technologists and three laboratory
technicians. It functions according to international Good
Laboratory Practice (GLP) standards and undergoes yearly
external quality assurance and quality. The laboratory is capable
of conducting the majority of tests required for HIV-NAT studies.
These include haematology, chemistry, T-cell subsets, viral load
assays and genotypic resistance assays. It also functions as
the central laboratory for two multi centre trials, the Thai Ministry
of Public Health ACTT002 study and the ESPRIT study. Current
projects are:
" Cross-clade HIV specific CTL responses in clade E/A
HIV-infected Thais
"Genotypic resistance in a sub-type A/E infected Thai
Cohort treated for a prolonged period with d4T and
ddl.
" HIV-1 gag-CTL epitope mapping in clade A/E infected
Thai patients
Development of a specific DNA vaccine for Thai clade
HIV-1 subtype A/E.
Multi-strain HIV infection