Abstract Book Vol. 2 [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

XIV International AIDS Conference

Abstracts ThPeB7208-ThPeB7211 389

pression after quadruple (QUAD) HAART initiated at the time of primary HIV-1
infection (PHI).
Methods: Pts were part of the QUEST cohort treated with Combivir-abacaviramprenavir at the time of PHI. Following viral suppression, pts remained on QUAD
or switched to TR. Two analyses were performed on subsets of pts with the following viral load (VL) profiles: a) 2 VL <50 c/mL without changing initial QUAD
regimen, n=68; b) 2 VL<10c/mL without changing QUAD (n=47). The analyses
examined time to two viral breakthrough (>50c/mL for group a or to >10c/mL
for group b. The effect of switching to TR was examined by including this as a
time-updated covariate as pts switched to TR at different times during follow-up.
Time to viral breakthrough was censored if patients stopped all HAART Results
are expressed as hazards ratios (HR 95% CI).
Results: Majority of pts remained on Comb/ABC- a few who had ABC hypersensitivity were given an alternative NRTI. Of the 68 pts who maintained VL <50
c/mL on QUAD, 27 switched to TR (stop PI in 26 cases and 1 NRTI in 1 case).
14/68 had viral breakthrough to >50 c/mL: 7.6% and 12.3% at W12 and W24,
respectively. No association was found between switching to TR and time to viral
breakthrough, HR 0.94 (0.18, 5.03), p= 0.9]. Among the 47 pts with VL<10 c/mL,
25/47 had VL>10 c/mL (28.9% and 48.1% by W12 and W24, respectively). TR
was again not associated with viral breakthrough >10 c/mL: HR 0.81 (0.07,9.39),
p=0.9.
Conclusions: These preliminary results suggest that switching from QUAD to TR
after viral suppression in PHI is not associated with increased viral breakthrough.
Further analyses based on a larger number of pts will be presented together with
comparison of CD8/CD38 and cell-associated HIV RNA and DNA measures.
Presenting author: sabine kinloch, department of immunology, royal free hospital, rowland hill street, london nw3 2qg, United Kingdom, Tel.: [phone],
Fax: [phone], E-mail: [email protected]
ThPeB7208 Factors contributing to reported high defaulter
rates among patients on TB treatments
Y. Taidhi1, S. Kapere2, R. Serunkuma2, M. Sonko2, D. Magezi2. 1The AIDS
Support Organisation, The AIDS Support Organisation, (TASO) Mulago, PO Box
11485, Kampala, Uganda; 2 TASO (U) Ltd, Kampala, Uganda
Background: In Kampala Kisenyi suburb of Uganda up to 40% have been
recorded as defaulters in a cohort.
Methods: A cross-sectional retrospective review of TB records and observation
of care given to TB patients was done at one of the health centres with a larger
TB case load. Suspected defaulters were visited and inerviewed. Focus group
discussions were done with defaulters, those just commenced, and about to complete treatment, members of health committee and health staff.
Results: The incidence of TB in 2001 was 49/10,000. The actual defaulter rate
was 9,8%. Those who died represented 18%, while 35,5% had left residence.
20% gave false address. 10,7% were regularly taking drugs. 5,6% could not be
reached. DOTS was not strictly followed. Patients complained of long waiting
time. Component of health education was lacking. Fear of divorce contributing
to none-adherence among women. Those who did not improve were associated
with HIV/AIDS.
Conclusions: Poor statistics are alrgely responsible for reported high defaulter
rates. From other findings in the study DOTS is not being practised correctly. Participation of peer educators and family members could improve compliance.
Presenting author: Yakubu Taidhi, The AIDS Support Organisation, (TASO) Mulago, PO Box 11485, Kampala, Uganda, Tel.: [phone], Fax: +256 41
541999, E-mail: tasomul @ infocom.co.ug
ThPeB7209 I Prevalence of resistance associated mutations in
antiretroviral drug naive Zambians infected with
subtype C HIV-1
R. Handema1, H. Terunuma1, F Kasolo2, H. Kasai1, A. Yamashita 1,
D. Xuewen1, N. Yamamoto3, M. Ito'. 'Yamanashi Medical University
Department of Microbiology Yamanashi, Japan; 2 Virology Laboratory University
Teaching hospital, Lusaka, Zambia; 3 oy Medical and Dental University
Tokyo, Japan
Background: The ability of the HIV-1 to evolve resistance to specific antiretroviral
agents leads to treatment failure. Amino acid residues responsible for resistance
have been identified through sequence analyses of the pol region of subtype B
HIV-1. We assessed the prevalence of drug resistance associated mutations in
antiretroviral naive individuals infected with subtype C HIV-1 in Zambia.
Methods: Twenty-eight antiretroviral drug na-ve individuals were recruited into
this study in 2000. Proviral DNA of HIV-1 was extracted from peripheral blood
mononuclear cells. The protease and reverse transcriptase gene coding regions
were amplified using the polymerase chain reaction followed by direct sequencing. Sequence analysis for detection of drug resistant mutations in the protease
and reverse transcriptase genes and phylogenetic analysis were done.

Results: Twenty six cases were of subtype C, one subtype A, and one suspected
C/A recombinant HIV-1. The most frequent mutations were 193L (91.7%), L89M
(79.2%), and M361/V (79%, 4.2%) in the protease gene, and R21 1 K (70.8%),
S48T (62.5%) in the RT Atypical amino acid residues 41N and 67A were also
detected in the RT gene.
Conclusions: Many natural occurring polymorphisms associated with drug resistance in the protease and RT genes of subtype C HIV-1 have been detected in

this study with the protease gene bearing more. Such mutations may lead to rapid
treatment failure and development of drug-resistant HIV-1 mutants, a concern in
clinical management of HIV-1 treatment.
Presenting author: Ray Handema, Department of Microbiology, Yamanashi
Medical University, Nakakoma-Gun, Tamaho-Cho, Yamanashi 409-3898, Japan,
Tel.: [phone], Fax: [phone], E-mail: [email protected]
ThPeB7210 Early experience with baseline hiv genotyping
Daniel Warner. Consultive Medicine, 426 Lambert Ave., Flagler Beach, Florida,
32136, United States
Background: Transmission of drug resistant HIV-1 strains is increasing. Drugnaive HIV patients with primary and/or secondary mutations are significantly more
likey than patients without mutations to fail antiretviral therapy at 24 weeks.
Methods: 49 HIV antiretroviral naive patients were randomly chosen after testing HIV positive. Patients initiated HAART after a baseline genotype. Recruited
in 1999, 69% were male and 31% female with a median age of 38, baseline viral load of 102,561 copies/ml, and a median CD4 count of 300 cell/mm3. Thirty
patients complete 6 months of therapy with 5 lost to follow up. HAART was determined at the physican's discretion based on appropriateness for individual patients.
Results: 5 of 49 genotypes detected a primary mutation(L101,1184V,L90M, and
D30N). 20 of 49 genotypes had secondary mutation (164M,V771,M361, and A71V).
2 genotypes had both. These patients were placed on regimens that did not
include antiretroviral medications associated with these mutations. There were
no significant differences in the number of patients who reached undetectability (<50copies/ml) based on genotypes. There was trend towards improved viral
suppression in patients with no mutations. Patients with no baseline mutations
had a higher chance of achieving an undetectable state and maintaining it for
6 months. Interestingly, there were no significant trends for a higher CD4 count
based on the presence of baseline resistance, leading one to think that immune
reconstitution is possible even if there exist some baseline resistance to current
available antiretroviral agents.
Conclusion: The first HAART regimen remains the best chance at achieving
success with antiretroviral therapy, an undetectable viral load. Even with baseline
mutations immune recovery remains possible. These results suggest that resistance testing at baseline should be considered for the optimal design of first line
therapy
Presenting author: Daniel Warner, 426 Lambert Ave., Flagler Beach, Florida,
32136, United States, Tel.: [phone], Fax: [phone], E-mail:
[email protected]
ThPeB721 1 The impact of transmitted drug resistance on time
to CD4 <350 cells/ml
K. Porter1, D. Pillay2, on behalf of UK Register of HIV Seroconverters1. IMRC
Clinical Trials Unit, MRC CTU, 222 Euston Road, London, United Kingdom;
2PHLS Antiviral Susceptibility Reference Unit, Birmingham, United Kingdom
Background: the prevalence of transmitted drug resistant (TDR) HIV has increased since HAART became available, potentially compromising the efficacy
of therapy in such individuals. However, there is in vitro evidence that such resistant species of virus have reduced replicative capacity. Our objective is to estimate whether progression to CD4 <350 cells/ml in untreated individuals differs
by whether or not they were infected with TDR HIV.
Methods: Nucleotide sequencing of the RT and PR genes of plasma virus were
undertaken on patients enrolled in the UK Register of HIV Seroconverters. All
were tested within 18 months of an antibody negative test before starting antiretroviral therapy (ART). Drug resistance was defined as the presence of one
or more key mutations in RT or PR recognised as causing reduced drug susceptibility. A person was considered to have reached CD4 <350 cells/ml only if the
following count was also <350 and was not within 6 months of seroconversion
(SC). We estimated time to CD4 <350 cells/mI using Kaplan-Meier and censoring at initiation of ART. Proportional hazard models were used to investigate the
effect of TDR HIV, adjusting for sex; age; year of negative test; exposure category;
and SC illness.
Results: Of 101 genotyped seroconverters infected between June 1994 and July
2001, 22 (22%) had evidence of RT and/or PR gene mutations associated with
reduced drug susceptibility. Overall, 16 persons reached a count <350 cells/mI
with 3 year progression estimate (95% CI) of 30.6% (17.7- 49.6%). There was
no evidence that progression differed between those with TDR HIV compared to
those with wild-type HIV [RR (95% CI)= 1.13 (0.32- 4.00), p=0.85].
Conclusion: From these initial findings there is no evidence to suggest that progression of HIV infection in the absence of therapy is affected by TDR. However,
ongoing monitoring is crucial as current followup is limited.
Presenting author: Kholoud Porter, MRC CTU, 222 Euston Road, London,

United Kingdom, Tel.: [phone], Fax: [phone], E-mail: k.porter
@ctu.mrc.ac.uk