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

72 Abstracts WePeB5970-WePeB5973

XIV International AIDS Conference

Results: Of 132 women with dyskaryosis, 99 had follow up data for analysis. Of
114 events (Pap t + Pap t+1), 25 began with HSIL and 89 with LSIL at Pap t.
HAART was used in 10.5% between Pap t and Pap t+1. Four women progressed
from LSIL to HSIL, 69 regressed (8 from HSIL to LSIL, 9 from HSIL to normal and
52 from LSIL to normal) and 41 persisted (33 at LSIL and 8 at HSIL). No progressions were seen from HSIL to invasive carcinoma. Overall rates were: progression
3.4 per 100 PY, regression 58.31 per 100 PY and persistence 34.7 per 100 PY
None of the 4 progression and 41 persistence events included HAART at time t
versus 17.4% (12/69) of regression events. High risk HPV types were detected in
85 samples of the 69 pairs that regressed with 29% losing high risk HPV types,
4% gaining and 54% remaining unchanged at time t+1.
Conclusions: In this cohort of HIV infected women with dyskaryosis, HSIL
was frequent (22%). Although regression was often encountered in HIV-infected
women, it could not be specifically correlated with HAART Further identification
of factors predictive of regression will be important in clinical practice.
Presenting author: Catherine Hankins, 1301 Sherbrooke east, Montreal, Quebec, H2L 1M3, Canada, Tel.: [phone] ext 3605, Fax: [phone],
E-mail: [email protected]
WePeB5970 A comparison of the pharmacokinetics of
nelfinavir in African-American women versus men
with HIV infection
R. Sharma1, B. Bellantone2, D. Singh3. 1The University Hospital & Arnold
&Marie Schwartz College of Pharmacy, 15 Knolls Drive, New Hyde Park, NY,
11040, United States; 2Arnold & Marie schwartz College of Pharmacy, Brooklyn,
United States; 3Nova Southeastern University North Miami Beach, United
States
Background: Studies evaluating nelfinavir (NFV) pharmacokinetics are scanty
and have been mostly performed in males. The pharmacokinetic parameters of
NFV 1250 mg twice daily (BID) have been examined in only one published abstract. We conducted a study to evaluate the steady-state pharmacokinetics of
NFV 1250mg BID in HIV+ females vs. males.
Methods: African-American HIV+ patients (15 males and 15 females) were enrolled. All were taking NFV 1250 mg BID on a chronic basis and assumed to be
at steady state. Eight patients were excluded from the final analysis for various
reasons. The first blood sample (t=0 hr) was taken just before the next scheduled
oral dose, and samples were subsequently collected for 12 hours. Free NFV concentrations were determined using HPLC by Agouron Pharmaceuticals. The data
was fit to a one compartment open model, with first order absorption and elimination. Nonlinear regressions were used to obtain estimates for the pharmacokinetic
parameters.
Results: Despite significant interpatient variability, the pharmacokinetic parameters of NFV in females vs. males were not statistically different. The time to
peak concentration(Tmax), oral clearance, and apparent volume of distribution
(Vd) found in this study were similar to values reported in the literature. The peak
concentration(Cmax), average steady state concentration(Cssavg), trough concentration(Cmin) and AUC (area under the curve) were higher than previously
reported values.
Parameter Males Females
Cmax(mcg/mL) 5.60~2.53 5.86~1.38
Tmax(h) 4.18~2.90 3.62~0.65
Cssavg(mcg/mL) 3.49~2.03 3.43~0.92
Cmin (mcg/ml) 1.34~1.64 1.26~0.74
T1/2 (h) 3.83~2.71 3.85~1.58
Ke(h-1) 0.24~0.10 ).20~0.07
AUCO-12(mcg-h/mL) 41.95~24.36 41.24~11.06
Oral CI (L/h) 45.73~36.22 32.12+7.65
V(L/kg) 2.47~1.21 2.61~1.12
T1/2=half-life Pvalue < 0.05 in all cases
Conclusions: The findings suggest that NFV 1250 mg BID with food produces sustained, elevated average plasma concentrations, and minimum plasma
concentrations several times higher than inhibitory concentration (IC95) (0.039
mcg/ml). The interpatient variability may result from variability in hepatic activity of CYP3A4 between HIV+ males and females, and complex mechanisms of
protease inhibitors clearance.
Presenting author: roopali sharma, 15 knolls drive, new hyde park, ny, 11040,
United States, Tel.: [phone], Fax: [phone], E-mail: rsharma
~ netmail.hscbklyn.edu
WePeB5971 Dyslipidaemia in HIV-infected women before and
after starting highly active antiretroviral therapy
(HAART)
M. Pynka. Dept. of Infectious Diseases, Pomeranian Academy of Medicine,

Dept of Infectious Diseases, Arkonska 4, 71-455 Szczecin, Poland
Background: Altered lipid profile is described in naive as well as in patients under HAART Objective: to determine the lipid profile in women with stable HIV
infection before and after 6 months of HAART
Patients and methods: fasting triglycerides (TG), total cholesterol (TCh), HDL,
LDL and leptins were measured in 41 HIV+ naive women, 20-57 years of age

(mean 29.5~8.6) without active AIDS events, and repeated after 6 months in 20
women on HAART (12 - with PIs, 8 - on PI-sparing therapy). TCh:HDL ratio and
BMI were calculated in this group as well as in control group of 25 healthy women,
24-59 years of age (mean 32.8~7.2). Statistical analysis: t test.
Results: Body mass index (BMI) in HIV+ women (22.5~11.0 kg/m2) did not differ significantly when compared with control group (23.8~0.7 kg/m2). We found
higher TG (130~9.2 vs 87.0~10.5mg/dl in control; p=0,004) and lower HDL
(48.8~2.8 vs 68.4~3.9mg/dl; p<0.0001) in untreated patients. They had significantly lower (12.2~1.7 ng/ml) level of leptin when compared with controls
(23.3~2.9 ng/ml; p=0.001). There were no significant differences in TCh and
LDL levels between infected and healthy women (169.7~7.8 vs 184~8.7mg/dl
and 101.3~7.6 vs 106~7.7mg/di, respectively). TCh:HDL ratio was higher in
HIV+ women (3.8~0.2) than in controls (2.8~0.1), p=0.004. HAART lasting 6
months resulted in elevation of TG level (136.8~46.6 vs 189.7~105.8 mg/dl;
p=0.038), TCh (167.3~41.8 vs 194.0~49.2mg/dl; p =0.009) and HDL (42.9~12.8
vs 52.1 ~mg/dl; p=0.003), but did not change significantly LDL and TCh:HDL ratio.
Conclusions: 1. Some changes in lipid profile in our patients during first 6 months
of HAART may, partially, reflect the "normalization" of metabolic disturbances presented in HIV+ naive women.
2. Low level of leptin in clinically stable, non-wasted HIV+ women, remains further confirmation and could be part of neuroendocrine disorders observed in HIV
infection.
Presenting author: Magdalena Pynka, Dept. of Infectious Diseases, Arkonska 4,
71-455 Szczecin, Poland, Tel.: [phone], Fax: [phone], E-mail:
sawomir.9020177 @ pharmanet.com.pl
WePeB5972I Safety and efficacy of Lopinavir/Ritonavir in
women in a phase III study of Antiretroviral-Naive
subjects
P. Cernohous, B. Bernstein, J. Mosley, M. King, E. Bauer, E. Sun. Abbott
Laboratories, R48U, AP30-3, Abbott Laboratories, 200 Abbott Park Road, Abbott
Park, IL, United States
Background. Lopinavir/ritonavir (LPV/r) is a novel protease inhibitor (PI) that
achieves trough concentrations >75-fold above the EC50 of LPV relative to wild
type virus when dosed at 400/100 mg BID.
Methods. Study M98-863 is a multi-center, international, double-blind randomized study of 653 ARV-naive subjects treated with either LPV/r (N=326) or
Nelfinavir (NFV) in combination with d4T and 3TC. In an intent-to-treat (noncompleter=failure) analysis, the proportion of subjects with VL<50 copies/mL at
Week 60 was greater in LPV/r-treated subjects compared to NFV-treated subjects
(64% vs. 53%, p=0.004). This analysis compares the efficacy and safety of LPV/r
in female subjects (n=66) vs. male subjects (n=260) treated in the M98-863 study.
Results. Overall discontinuation rates were not significantly different between female and male subjects treated with LPV/r (26% vs. 21%, p=0.405). Study drugrelated discontinuations occurred in 5 of 66 females and 7 of 260 males. Triglyceride elevations were less common in women while nausea was less common in
men. Discontinuations associated with gastrointestinal related adverse events or
lipid elevations were uncommon. Week 60 efficacy results are presented in the
following table:
Efficacy variable Female Male p-value
%<50 HIV RNA copies/mL (OT) 83% 82% 0.857
%<50 HIV RNA copies/mL (ITT NC=F) 61% 65% 0.545
CD4 Mean Change from Baseline 257 cells/4L 244 cells/kL 0.629
Conclusions. Efficacy and safety were comparable between female and male
subjects treated with LPV/r in this blinded phase III study.
Presenting author: Judi Kruse, R48U, AP30-3, Abbott Laboratories, 200 Abbott
Park Road, Abbott Park, IL, United States, Tel.: [phone], Fax: [phone], E-mail: [email protected]
WePeB5973 A prospective study of HIV related hospitalization
rates during the HAART era in an urban and
HIV-referral hospital in Miami: gender and
ethnic/racial differences
H. Archer, M.J. Miguez-Burbano, A. Rodricjuez, X. Burbano, A. Pilarte,
N. Rodriguez, G. Shor-Posner. University of Miami School of Medicine, Miami,
United States
Background: Recent reports of a non-significant reduction in the rate of
HIV/hospitalizations suggests that HAART may have reached its threshold of effectiveness in reducing clinical morbidity resulting in hospital admissions.
Methods: Rates of hospitalization, discharge diagnosis, medical history, CD4
and viral load were obtained in HIV+ subjects consecutively hospitalized at Jack
son Memorial hospital (JMH) and recruited in a cross-sectional study (Sept-Dec
2001).
Results: 84 men and 57 women ranging in age from 20-62 (42~8) and HIVinfected for a mean of 6 years were hospitalized. Most patients (52%) were
African-American, 26% Haitian, 18% Hispanics and 4% white. The mean CD4
was 114~145 cells/mm3 and viral load was 353541~311378 HIV copies; no significant gender differences were observed. More than half (60%) of the partici