Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

336 Abstracts 22360-22364

12th World AIDS Conference

223601 Influence of antiretroviral combinations on disease
progression and survival in HIV infected patients,
Aquitaine (France), 1988-97
Frantz Thiessard, L. Dequae, R. Thiebaut, C. Marimoutou, F. Dabis,
R. Salamon, I. Gecsa. 1/nserm U. 330, Bordeaux 2, 146 rue Leo Saignat 33076,
Bordeaux, France
Objective: To assess the influence of the different antiretroviral treatment prescriptions on disease progression and survival among HIV positive patients
enrolled in the Aquitaine Cohort.
Design and Patients: Prospective multicentre cohort study. 2238 HIV-1 subjects with CD4 cell count under 200/mm3 enrolled between January 1st, 1988
and June 30th, 1997.
Methods: Two multivariate Cox models were performed to compare first, progression to AIDS and second, to death between 5 groups of treatment and the
never treated patients (N = 219). We used the following adjustment variables:
age, gender, HIV transmission group, year of enrollment in the study, clinical
stage, primary prophylaxis, CD4 cell count. The categories of treatment were
considered in intent to treat analysis.
Results: Monotherapy alone with a nucleoside analogue (N = 1006) did not
modify the risk of death compared to no antiretroviral treatment. Triple therapy
including 1 protease inhibitor in naive patients (RH = 0.07; Cl:0.02-.28; N =
66) and triple therapy with a history of mono and/or dual therapy (RH = 0.04;
Cl:0.03-0.06; N = 503) were the most protective factors for survival. Dual therapy
alone with two nucleosides analogues (RH = 0.26; C1:0.15-0.44; N = 128) and
dual therapy with a history of monotherapy (RH = 0.19; CI:0.14-0.25; N = 316)
were also associated with better survival than never treated patients. Monotherapy alone was a pejorative factor (RH = 2.80; Cl:1.78-4.40) of the risk of AIDS.
Other groups of treatment did not statistically modify the risk of AIDS.
Conclusion: These observational results confirm the reduction in mortality with
introduction of antiretroviral combinations, especially triple therapy with protease
inhibitors. Longer follow up or wider prescription may allow detection of the
beneficial effect of triple therapy on AIDS occurrence
1223611 Indinavir can be taken with regular meals when
administered with ritonavir
Ann Hsu, R. Granneman, M. Heath-Chiozzi, C. Wong, L. Manning, R. Brooks,
E. Sun. Abbott Laboratories, 100 Abbott Park Road, D4PK Bldg. 13A, Abbott
Park, IL, USA
Indinavir (IDV) and ritonavir (RTV) are potent HIV protease inhibitors. IDV is
rapidly metabolized by CYP3A. The bioavailability of IDV is reduced 80% after a
regular meal, probably partly due to protracted absorption related to meals. Thus,
IDV should be given 2 h after or 1 h before a regular meal. RTV is a CYP3A
inhibitor. We have previously shown that single doses of 400-600 mg IDV given
with 200-400 mg q12h ritonavir resulted in similar AUC (~30%), lower peak and
higher trough concentrations as compared to those from standard 800 mg IDV
q8h regimen. In this study we evaluated steady-state (SS) IDV and RTV pharmacokinetics in the presence or absence of regular meals. Nine healthy volunteers
received 1200 mg IDV q12h on Day 1,800 mg IDV q8h on Day 2, and RTV+IDV
(400 mg each) q12h during Days 3 to 17. The Days 1-16 doses were given under
fasting conditions or after a low fat snack. The Day 17 doses were given after a
regular (35% fat) breakfast and dinner. Compared to the standard regimen (Day
2), the SS Day 17 IDV AUC24 in the RTV+IDV regimen was essentially identical
(ratio = 1.0, 90% Cl = 0.81-1.3), the C24 was substantially higher (ratio = 3.6, 90%
Cl = 2.1-6.1), and the Cmax was sig. lower (ratio = 0.41, 90% Cl = 0.35-0.48).
When RTV+IDV were given after a low fat snack (Day 16, 370 Kcal with 5% fat
calories), the SS IDV AUC24 was also similar (ratio = 1.1, 90% CI = 1.0-1.3), the
C24 was higher (ratio = 3.1, 90% Cl = 1.9-5.0), and the Cmax was lower (ratio
= 0.52, 90% CI = 0.45-0.60). In contrast, compared to IDV q8h regimen, the
1200 mg IDV q12h alone regimen yielded sig. lower C24 (ratio = 0.31, 90% Cl =
0.25-0.40), and sig. higher AUC (ratio = 1.4, 90% Cl = 1.3-1.6) and Cmax (ratio
= 1.6, 90% Cl = 1.5-1.7). RTV PK were not affected by food.
Overall, we have shown that IDV+RTV can be taken with or without food. The
combination of these two drugs will be evaluated in HIV-infected patients.
22362 Combination therapy with nelfinavir, stavudine and
lamivudine (HAART) in HIV-1 infected children: Kinetics
of immune reconstitution
Henriette J. Scherpbier1, M.T.L. Roos2, N.G. Pakker2, F. De Wolf3,
S. Jurriaans3, F. Miedema2, J.M.A. Lange4. 1Academic Medical Center (AMC),
Amsterdam; 2Clin. Viro-JMM.CLB, Amsterdam; 3Human Retriovirology AMC,
Amsterdam; 4JNF. Disease, Trop. Med, & AIDS, NATEC, AMC, Amsterdam,
The Netherlands
Objectives: To evaluate the effect of treatment with a combination of nelfinavir,
stavudine and lamivudine (HAART) on the immune reconstitution in HIV-1 infected
children.

Design: Prospective, open study.
Methods: Vertically HIV-infected children (confirmed by HIV-RNA PCR) were
included when the following criteria were met: viral load (Nuclisens, Organon
Teknika) repeatedly above 5,000 copies/ml and/or CD4' T-cell counts below the
age-threshold, according to the CDC-criteria. HAART-treatment was given in the
following daily dosages: nelfinavir 90 mg/kg, stavudine 2 mg/kg, lamivudine 8
mg/kg. Viral load and T-cell subsets (CD41 and CD81 T-cell counts), their acti
vation state (CD38/HLA-DR), the change in naive and memory (CD45RA/CD27)
subpopulations and T-cell function in vitro were determined two weeks before, at
the start of protocol-treatment, and during follow-up at 1, 2, 4, 8, 12 weeks and
subsequently every 3 months.
Results: Nine consecutive children (6 girls) were included (mean age 4.1 yrs,
range 1 mth to 8 yrs). All but 2 children had previously been treated with different
antiretroviral regimens. The follow-up was at least 30 days and maximally 100
days. The HIV viral load decreased below detection level (<400 copies/ml) within
4 weeks in 5 children and in 4 children within 5-12 weeks. Both CD4~ and CD8+
T-cell counts increased significantly in all children in the first 3-6 weeks. An
increase in numbers of naive cells was shown in only the two children <1 year
of age. In children with low CD4+ baseline counts memory cells increased. A
substantial improvement of T-cell reactivity to CD3mAb+CD28mAb compared to
baseline values was observed in all children.
Conclusion: These preliminary data indicate that HAART in HIV-1 infected
children results in a decrease of the viral load below the detection level; an
increase of the CD4~ and CD8~ T-cells is demonstrated in the first 3-6 weeks,
which is related to a rise of naive cells in children <1 year only. Our data show
that the restoration of the immune system in children may be as slow as in HIV-1
infected adults.
223631 Predictors of success of antiretroviral therapy (ART) in a
prospective clinic cohort
MichaelS. Saag1, G.C. Cloud1, J. Raper1, J.M. Tolson2, S. McKinnon1,
A. Gum1, S. Call1. 1University of Alabama at Birmingham 908 20th Street, South
Birmingham AL; 2Glaxxo Wellcome Re. Triangle Pk. NC, USA
Background: With the availability of 11-plus antiretroviral agents and the routine
use of viral load in clinical practice, each patient develops a relatively unique
treatment history. We examined the impact of treatment history, along with other
factors, on virologic and clinical outcome in the UAB 1917 Clinic cohort.
Methods: Beginning in March, 1997, 120 HIV~ patients who were receiving
primary care at the UAB AIDS Outpatient Clinic were enrolled in a prospective
cohort study. Participants had HIV RNA values > 5,000 c/ml and were either initiating or changing ART at the time of enrollment. Clinical, laboratory, adherence,
QOL, health care utilization, and genotypic/phenotypic resistance evaluations
were performed every 3 months. Virologic success was defined as sustained
suppression of HIV RNA below 5,000 c/ml for the period of observation (median
F/U 8.2 months).
Results: The median baseline viral load was 64,618 c/ml and median CD4
was 162 c/ml. Among the 120 patients, 21 (18%) were ART naive at entry and
49 (41%) were PI naive. Clinical progression was observed in 14 patients; 11
developed a new 01; 5 died. Virologic success was observed in 49 patients (41%).
Factors associated with success included (by univariate analysis): no prior PI Rx
(76% success vs 17%; p = 0.0001) and no prior 01 (53% success vs 26%; p =
0.008). Successfully treated patients had lower viral load values at entry (35,855
vs 82,057 c/mL; p = 0.01) and fewer prior ART regimens (3.0 vs 5.0; p = 0.001).
Baseline CD4 was similar between the two groups (162 vs 163/uL; p = 0.70). Cox
proportional hazard analysis revealed prior PI Rx (RR 3.3; p = 0.0001) and higher
baseline viral load (RR 1.5; p = 0.0001) were associated with failure. Adherence,
QOL, and resistance data were not available at the time of analysis.
Conclusion: In the absence of adherence, QOL, and resistance data, factors
associated with ART failure (inability to achieve/sustain viral load < 5,000 c/mL)
were prior PI use and higher viral load at study entry. The pattern of prior ART
use appears to have a profound effect on virologic outcome.
122364 Effect of antiretroviral therapy on viral load and CD4
count in HIV infected children <36 months of age
Savita Pahwa, Saroj Bakshi, S. Patrick, M. Morales. North Shore Univ
Hosp-NYU School of Med Manhasset NY 11030, USA
Objectives: Therapeutic management of HIV infected infants is complicated due
to presence of high viral burden, and limited number of drugs available. The objective of this study was to evaluate virologic and immunologic response to treatment
in children <36 months old with currently available therapies. Methods: 8 children
with perinatal HIV infection, age range birth to <36 months, were followed in the
clinic for multi-disciplinary care. CD4 lymphocyte count (by FACS analysis) and
HIV RNA copies (by RT PCR, with a dynamic range of 400-750,000 RNA copies)
were determined at intervals of 3 month or more frequently if clinically indicated.
Results: The diagnosis of HIV infection was established in all children by age
3 m except in one, who was not tested till age 7 m. Only 1 of 8 mothers had
been identified as being HIV infected and given AZT during pregnancy. Viral load
at first testing (at <3 m of age in 6/8, and >6 m in 2/8) ranged from 2306 to
>750,000 (median 575,834) RNA copies. 6/8 children had very high viral load
of >400,000 copies. CD4% was normal in all children at initial testing except in
2 who showed moderate, or severe suppression. Patients were given 2 or more
RT1s, 2/8 received 1 PI + 2 RTIs. Undetectable or very low viral load (<3000
copies) was achieved in 5 children. In two infants, both ages 2 m each the follow

up has been short - 2 m. One child is a true treatment failure with RTIs, and is
intolerant of Pls. CD4 response was seen in all including the child considered to
have virologic failure. There were 2 AIDS defining events in 2/8 children, in both
before antiretroviral treatment was started.
Conclusion: HIV infected women continue to remain undiagnosed and untreated during pregnancy. Combination therapies with multiple RTIs with and
without PIs achieve virologic response in young infants. CD4 response may be