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

XIV International AIDS Conference

Abstracts WePeC6148-WePeC6151 119

unit, department of pathology, faculty of medicine, ramathibodi hospital, mahidol university, rama 6 road, ratchadaewee, bangkok 10400, Thailand, Tel.: [phone], Fax: [phone], E-mail: [email protected]
WePeC6148 A comparative, retrospective analysis of lipid
levels with relation to protease inhibitor dosage in
HIV-1 infected individuals treated with ritonavir
(RTV) versus nelfinavir (NLF) versus other
non-RTV containing anti-retroviral regimens
S.E. Hulse, S. Ballesteros, K.M. Bleichner. University of California Davis,
Medical Center, UCDMC, Divison of ID, 4150 V Street, PSSB, Suite 500,
Sacramento, CA 95817, United States
Background: Ritonavir (RTV) is commonly added to a regimen to boost the blood
levels and to reduce the dosage of other protease inhibitors (PIs) used in combination anti-retroviral therapies. RTV containing regimens were more likely to be
associated with increased cholesterol and triglycerides than NLF regimens. While
RTV is known to increase lipid levels, there is little data on the effect of dosage on
both cholesterol and triglyceride levels. Nelfinavir (NLF) was the most common
non-RTV containing regimen prescribed in this cohort.
Methods: A retrospective analysis was performed on a random number of HIV-1
infected patients (n=274) on HAART containing either single or combination PIs
who were seen at the CARES (Center for AIDS Research Education and Services) clinic in Sacramento, California from January 2000 through June 2001. Parameters included: Pl(s) prescribed, total daily dosage of PI, age, gender, cholesterol, LDL, HDL, LDL/HDL ratio and triglyceride levels. A logistic regression analysis was performed on the data to ascertain if there is a relationship between
protease inhibitors and lipid levels.
Results: There were 274 patients receiving a total of 9 regimens. There is no
statistical difference between nelfinavir (NLF) vs other non-RTV PI regimens
for either cholesterol or triglycerides. In comparing NLF vs RTV, there is increased risk for both high cholesterol (>240mg/dl) (p=0.008) and high triglycerides (>400mg/dl) (p=0.009) with RTV. There is a significant dose-response
relationship between RTV dose and high cholesterol (p=0.003) and high triglycerides (p=0.002).
Conclusions: An increase of RTV by 200mg/day multiplies the odds of having
both high triglycerides and high cholesterol by almost 1.5 times. This is clinically
relevant as 200mg is the increment in which the dosage of RTV is adjusted when
using RTV in boosted PI regimens. Clinicians must weigh risk versus benefit when
considering RTV dosage.
Presenting author: Susan Hulse, UCDMC, Divison of ID, 4150 V Street, PSSB,
Suite 500, Sacramento, CA 95817, United States, Tel.: [phone], Fax:
[phone], E-mail: [email protected]
SWePeC6149 I Prevalence of resistance and HIV-1 subtypes in
drug-naive patients
V. Duque1, A. Carvalho1, E. Rabado2, J. Oliveira2, J. Saraiva-da-Cunha2,
A. Meligo-Silvestre2. 1Laborat6rio de Virologia/Departamento de Doengas
Infecciosas/Hospitais da Universidade, Hospitais da Universidade de Coimbra,
Departamento de Doengas Infecciosas, Avenida Bissaya Barreto, 3000-075
Coimbra, Portugal,; 2Departamento de Doengas Infecciosas/Hospitais da
Universidade, Coimbra, Portugal
Background: Genetic variability is a central feature of HIV-1. The high frequency
of mutations during HIV-1 replication leads to the development of viral quasispecies in vivo and contributes to genetic heterogeneity among HIV-1 isolates.
Drug resistance patterns and subtypes are a manifestation of that variability. Preexisting drug related mutations can greatly affect antiretroviral treatment outcome.
Methods: To determine the prevalence of patients with primary and secondary
mutations. Cross-sectional study. 93 HIV-1 infected patients without any past antiretroviral treatment history enrolled in the Department of Infectious Diseases of
our hospital during the year 2000, were included. Direct sequencing of the protease and reverse transcriptase genes of plasma virions was performed. Primary
and secondary mutations were identified. Phylogenetic analysis was performed
in the protease gene.
Results: The prevalence of patients with primary and secondary mutations
were 3,22% (3) and 83,87% (78), respectively. Phylogenetic analysis shown that
88,17% (n=82) of the strains cluster within the group M. Subtype B represented
58,06% (n=54) of all subtypes. Non-B strains represented 30,10% (n=28). Intersubtype recombinant strains were found in 11,82% (n=l 1).
Conclusions: During the year 2000 the prevalence of HIV-1 infected patients
with primary mutations associated with resistance to antiretroviral drugs was low
in Portugal. The prevalence of the secondary mutation M361 suggested that a
high proportion of non-B subtypes might be present in the population studied.
Non-B subtypes originated in Africa have been introduced in the country and represented a higher than expected proportion in the population group studied.

Presenting author: Vitor Duque, Hospitais da Universidade de Coimbra, Departamento de Doengas Infecciosas, Avenida Bissaya Barreto, 3000-075 Coimbra, Portugal, Tel.: [phone], Fax: [phone], E-mail: viroinf@mail.
telepac.pt

WePeC6150 Antiretroviral resistance and diversity among
patients seeking HIV genotying in Sao Paulo,
Brazil
R. Rodrigues', R.M. Custodio1, L. Jamal2, M. Eira 3, A.J.S. Duarte4,
M.C. Gianna5, L.F.M. Brigido6. 'Adolfo Lutz Institute, Sao Paulo, Brazil;
2CRT-Aids -Sao Paulo, Sao Paulo, Brazil,; 3Emilio Ribas Institute, Sao Paulo,
Brazil; 4Sao Paulo University, SAo Paulo, Brazil; 5CRT - Aids -Sao Paulo, Sao
Paulo, Brazil; 6Ministry of Health -NAR Av Dr Arnaldo, 355 - Servico de
Virologia, 01246.902, Sao Paulo, Sao Paulo, Brazil
Background: Sao Paulo State has the largest number of patients using antiretroviral therapy (ART) in Brazil, with over 40,000 individuals receiving free medication. Albeit mortality and morbidity has fallen significantly in the last years, many
patients present virologic rebound. We describe here adult patients referred to the
State Central Public Health Laboratory to evaluate genotypic resistance pattern.
Methods: Samples from 130 heavily ART experienced patients were analyzed
either by direct DNA from cell pellets or reverse transcription of plasma RNA followed by amplification of reverse transcriptase (RT) and protease (PR) genes
with nested PCR. Sequencing was performed using dye terminator at ABI 377
sequencer.
Results: L90M and V82A/T were the most frequent principal mutations to protease inhibitor (IP), present alone or in combination in 54% of cases. IP specific
mutations, as 150V or G48V are not observed, and D30N in only 3% of samples, albeit 45% of the patients had used Nelfinavir at some point, for a median
time of 9 months. At RT, residues T215 (59%), M184 (44%), K70 (21%) and V118
(18%) were the most common principal mutations to analogous nucleosides (AN).
K103R, G190A/S and Y181C to non-AN inhibitors, in 21%, 18% and 20% of cases
respectively HIV-1 B was the predominant subtype in PR (81%), followed by F
(9.7%) and D (1.3%). One tenth of HIV-1 B PR had other subtype or recombination at RT Evidence for recombination within PR, was observed in 8%. On RT
74% were B, 4.2% F and 22% had evidence of recombination.
Conclusions: Frequent principal mutations at RT and PR, associated with many
secondary polymorphism, affecting more then one drug in each class may justify the virological failure of these patients. Selection of patients that can benefit
most of test is an important goal to maximize its benefit. Frequent recombination may pose new problems by the introduction of polymorphism that may act as
secondary mutations.
Presenting author: Rosangela Rodrigues, Av Dr Arnaldo, 355 - Servico de Virologia, 01246.902, Sao Paulo, Sao Paulo, Brazil, Tel.: [phone], E-mail:
rohc@ usp.br
WePeC61 51 Resistance profile among HIV-infected patients
with virological failure seen in a public health
university clinic at Sao Paulo city, Brazil
N. Gaburo1, L.F.M. Brigido2, J. Casseb3, R. Rodrigues4, R. Alcaide4,
C.R. Gonsalez4, A.J.S. Duarte4. 1Sao PAulo University- FMUSP - L/M56, Sao
Paulo, Brazil; 2Adolfo Lutz Institute, Sao Paulo, Brazil; 3Sao Paulo University,
Sao Paulo, Brazil; 4Sao Paulo University-FMUSR Sao Paulo, Brazil
Background: Appearance of codon mutations, which confer in vitro and in vivo
drug resistance to antiretroviral therapy, is a public and clinic healthy problem. We
studied here all accessible patients followed at a public university clinic at the city
of Sao Paulo to determine HIV drug resistance pattern.
Methods: Samples from 65 patients, 56 with a median plasma viremia of 4.92
and 9 with undetectable viremia at last measurement, were analyzed for HIV
genotype by extraction of DNA from cell pellets followed by amplification of reverse transcriptase (RT) and protease (PR) genes with nested PCR. Sequencing
was performed using dye terminator in an ABI 377 sequencer.
Results: The most common principal mutation to protease inhibitor (IP) was L90,
noted in 31% samples, followed by V82 in 15%. At RT, T215 (32%), M184 (27%)
and V118 (20%) were the most common mutations associated with NARTI, and
K10i3R, in 12%, was the most common mutation to NNRTI. Rare principal mutations were observed among most aviremic, L90M, V82 and 184 was observed, all
associated with previous use of IP. One had K103 and another G190 but with no
additional mutations to other drugs in the regimen. Mutations at M41, K70 and
D67 at RT were associated with previous AZT containing regimens. Frequent
polymorphism was observe in both viremic and aviremic, as at L63 (62% x 56%)
and M36 (38% x 44%), respectively. Salvage therapy containing Efavirenz was
used significantly more frequent then among viremic patients (p<0.05, fisher exact test).
Conclusions: ART failure was associated with different resistance mutation patterns, but multi-PI, AZT and 3TC related mutations were most commonly observed. None of aviremic patients had principal mutations to more then one drug
in the regimen. The prevalence of polymorphism that may act as secondary mutations to IP was similar in the two groups. Regimens with low pill burden were
associated with undetectable viremia. Support: FAPESP 99/10620.
Presenting author: Rosangela Rodrigues, Av Dr Arnaldo 455 sala 2345 - LIM56,

cep 01246903, Sao Paulo, Brazil, Tel.: [phone], E-mail: [email protected]