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

390 Abstracts ThPeB7213-ThPeB7215

XIV International AIDS Conference

ThPeB7212 Incidence of HIV-1 Drug Resistance (DR) from 1996
to 2001 in the Montreal Primary HIV Infection
Cohort
J.P Routy1, B. Brenner2, S. Bruce1, B. Spira2, M. Legault1, D. Moisi2,
D. Rouleau3, PR Cote4, R. Thomas5, R.G. Lalonde1, R. Leblanc6, M. Petrella2
R.P. Sekaly5, M. Wainberg2. 'McGill Health Centre Immunodeficiency Service
Department, royal victoria hospital, 687 ave. des pins west, c6.92, montreal,
quebec, h3a la 1, Canada; 2McGill University AIDS Centre, McGill University,
Montreal, Canada; 3CHUM Notre-Dame Hospital, Montreal, Canada; 4Private
Medical Clinic, Montreal, Canada; 5Department of Microbiology and
Immunology, University of Montreal, Montreal, Canada; 6McGill Health Centre
Immunodeficiency Service Department, Private Medical Clinic, Montreal,
Canada
Objective: The recommendations of the International AIDS Society-USA (IAS)
released in 2000, suggested delayed treatment for certain HIV patients. We hypothesized that this new therapeutical strategy would impact on the prevalence of
HIV-1 drug resistance (DR) among newly infected patients after the year 2000.
Methods: From May 1996 to December 2001, pre-treatment plasma samples
from newly infected patients were genotyped for changes in reverse transcriptase
(RT) and protease, using the Visible Genetics TRUGENE automated sequencing. The prevalence of DR in 141 patients was stratified according to year and
route of infection. We used IAS panel recommendations for the categorization for
mutations conferring DR.
Results: Throughout the study the proportion of patients presenting with different routes of infection remained similar. Mutations conferring resistance were
grouped according to classes of nucleoside (NRTIs), non-nucleoside (NNRTIs),
primary protease inhibitors (PI), secondary PI mutation accumulations, triple
class resistance and clades. Dual or triple MDR class mutations were present
in10 of 14 patients.
Year Total Pt. with NRTI NNRTI 1oPI 20 P1 2' PI 20 PI MDR 3
Patients any DR mutation none >1 & <3 >3 class.
1996 4 25% 25% 25% 0% 25% 50% 25% 0%
1997 46 13% 9% 4% 9% 20% 54% 22% 2%
1998 39 3% 3% 3% 0% 18% 69% 13% 0%
1999 17 18% 18% 6% 12% 6% 82% 12% 6%
2000 15 7% 0% 7% 7% 0% 73% 27% 0%
2001 20 5% 0% 0% 5% 50% 50% 0% 0%
Conclusions: These results suggest that the incidence of DR has decreased in
2001 in Montreal for both RT and protease. This may reflect that the HIV-infected
population is treated later in the course of infection than before 2000, when
the philosophy was to "treat-hard-and-early". A multi-centre North-American DR
study is ongoing to confirm these trends.
Presenting author: jean-pierre routy, royal victoria hospital, 687 ave. des pins
west, c6.92, montreal, quebec, h3a lal, Canada, Tel.: [phone], Fax:
[phone], E-mail: [email protected]
ThPeB72133 Prevalence of HIV-1 drug resistance mutations in
patients with primary HIV-1 infection (PHI) in
Barcelona (Spain)
M. Arnedo, J.M. Mir6, T. Pumarola, C. Gil, X. Claramonte, A. del Rio, J. Joseph,
M. Plana, J.L. Blanco, F. Garcia, E. Martfnez, J.M. Malloles, T Gallart,
J.M. Gatell. Hospital Clinic-IDIBAPS Barcelona, Hospital Clinic de Barcelona,
Villarroe/l170, Servicio Microbiologia, esc. 11 planta 5, Spain
Objective: To determine the prevalence of drug resistance-conferring mutations
to antiretroviral agents in a cohort of patients with primary HIV-1 infection (PHI) in
Barcelona (Spain) during the last five years (1997-2001).
Patients: 47 consecutive cases diagnosed of PHI between May 1997 and December 2001.
Methods: HIV-1 infection was diagnosed by ELISA (Axsym, Abbott) and confirmed by Western-blot (Sanofi-Pasteur). Plasma HIV-1RNA levels were determined using the Amplicor Assay (Roche). Population-based sequencing of viral
reverse transcriptase and protease regions to detect genotypic resistance mutations was done in plasma samples using the ViroSeq HIV Genotyping v.2 system
(Applied Biosystems). Plasma HIV-1 viral load, and genotypic analysis were done
during the acute PHI phase or within 90 days since the beginning of the symptoms. Bulk sequencing of proviral DNA was performed 1 year after the PHI in
those patients with primary mutations.
Results: PHI infection was symptomatic in 41cases(87%). 29(13,63%) patients
were homosexual men, 9(4,23%) heterosexual and 9(4,23%) i.v. drug abusers.
The mean (range) age was 35 (20-50) and 80% of cases were male. PHI was
diagnosed in 1997,1998,1999,2000 and 2001 in 10,8,14,5 and 10 cases respectively.At baseline mean plasma VL was 356.998 copies/mL (range 3236- 106).
All cases were by HIV-1 B subtype. Primary mutations were detected in 4 pa
tients (9.1%). Resistance mutations to NRTI were detected in 1(2,1%) patient, to
NNRTI in 2 patients(4,7%), and to IP in 1(2,1%) patient. Resistance mutations
to at least two antirretroviral families were detected in 2(4,2%) cases. Multidrug
resistance-conferring mutations were not detected.
Conclusions: In Barcelona (Spain), the prevalence of HIV-1 drug resistanceconferring mutations to antiretroviral agents in patients with PHI was 9,1%. The
determination of genotypic mutations may be very useful in this setting in order to
guide the first antiretroviral regimen.

Presenting author: Mireia Arnedo, Hospital Clinic de Barcelona, Villarroel
170, Servicio Microbiologia, esc.11 planta 5, Spain, Tel.: [phone], Fax:
[phone], E-mail: [email protected]
ThPeB7214I4 Transmission of drug resistant virus in primary
HIV-1 infection
M. Brady, S. Fidler, J. Clarke, J. Weber. Imperial College, Clinical Trials Centre,
Winston Churchill Wing, St Mary's Hospital, Praed Street, London W2 1NY
United Kingdom
Background: Widespread and increasing use of antiretroviral therapy (ART) has
led to rising prevalence of drug resistant strains of HIV-1. Transmission of these
strains compromises future treatment options of newly infected patients. We report the prevalence of resistant virus strains in a cohort of patients with primary
HIV-1 infection (PHI).
Methods: PHI was defined as a negative HIV test in the previous 6 months, negative/evolving HIV antibody tests with positive HIV PCR and/or symptoms of HIV
seroconversion. Genotypic resistance testing using ABI Viroseq version 2 was
performed at baseline.
Results: 44 patients have been recruited (43 gay men, 1 heterosexual woman).
Median age (range) was 30 (21-77). Median (range) CD4 count and viral
load at baseline were 465 cells/mm3(90-1200) and 122,298 RNA copies/ml
(179-*500,000). All infections were sexually transmitted. Baseline resistance results are available on all 44 patients. 40/44 (91%) were subtype B. All non-B
subtype infections were acquired in Africa. 42/44 (95.5%) were wild type virus.
Only 2 patients in the cohort (4.5%) had acquired a drug resistant virus. Both are
gay men, one infected in Australia and one in the UK. The first had mutations
M184V, G196E, L63P, G73S, V771 and L90M which fitted with his HIV+ partner's
drug history. The other patient had mutations M41L, A98G, M184V, Y188L and
T215Y. This doesn't fit with his HIV+ partner's treatment history, but he had multiple sexual partners suggesting an alternative source of infection.
Conclusions: We report a much lower prevalence of drug resistant virus in primary infection compared with previous studies. These data are encouraging, but
this may reflect the nature of the cohort. Transmission of drug resistant virus
appears to be an increasing problem and rapid genotypic resistant testing is essential in the context of treating primary HIV-1 infection.
Presenting author: Michael Brady, Clinical Trials Centre, Winston Churchill
Wing, St Mary's Hospital, Praed Street, London W2 1NY, United Kingdom, Tel.:
[phone], Fax: [phone], E-mail: [email protected]
ThPeB7215 Prevalence of genotypic antiretroviral
drug-resistant HIV-1 strains among naive children
A. Afonso, E.S. Machado2, J.S. Lambert3, E. Caridel, S.M. Cunha4,
R.H. Oliveira4, A. Tanuri1. 1 Universidade Federal do Rio de janeiro, Rua Coronel
Veiga 119 casa y Centro - Petropolis Rio de Janeiro CEP 25655150, BRAZIL,
Brazil; 2Servigo de Doengas Infecciosas e Parasitirias, Hospital Universitario
Clementino Fraga Filho, UFRJ, Rio de Janeiro, Brazil; 3Institute of Human
Virology, University of Maryland, Baltimore, United States; 4Instituto de
Puericultura e Pediatria Martagao Gesteira (IPPMG), UFRJ, Rio de Janeiro,
Brazil
Background: The emergence of HIV-1 mutations that confer resistance to antiretroviral agents is a major cause of treatment failure. Furthermore, motherchildren transmission of these viral variants has been reported. We have performed a study to assess the presence of reverse transcriptase (RT) and protease (PR) resistance mutations in antiretroviral naive children from IPPMG, Rio
de Janeiro.
Methods: Thirty-seven antiretroviral naive vertically HIV-1 infected children were
evaluated. Genotypic drug resistance was assessed sequencing the RT and PR
genes derived from plasma HIV RNA. C2V3 loop was also analyzed.
Results: Eighty-nine percent (n=33) of virus isolates have shown at least one
codon change associated with drug resistance, and 14% (n=5) have shown triple
substitution. Drug resistance mutations were found in the PR region in 86%
(n=32) of the sequences. The frequency of alterations was as follows: 63P (57%)
> 771 (28%) > 101/V, 361 (26%) > 93L (11%) > 20R/M and 71T (6%) > 10K/S,
63A and 93V (3%). In the RT region, 211K and 214L NRTI resistance mutations
were the more frequent, with 54% (n=20) and 18% (n=6) of prevalence respectively. Additionally, two patients present in RT gene the 1061 change related to
NNRTI resistance. Phylogenetic analysis of pol gene and C2V3 loop revealed a
total of 5 isolates that cluster with F subtypes and 32 with B subtypes. Two isolates were B/F recombinants.
Conclusions: No primary resistance mutations were detected in this study.
Therefore, a high prevalence of secondary substitutions in the protease was verified. The impact of this alterations in the therapeutic regimen in antiretroviral
therapy deserves furthers investigations.
Presenting author: Adriana Afonso, Rua Coronel Veiga 119 casa y Centro -

Petropolis Rio de Janeiro CEP 25655150, BRAZIL, Brazil, Tel.: [phone],
Fax: [phone], E-mail: adriaff@ biologia.ufrj.br