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

338 Abstracts 22370-22374

12th World AIDS Conference

Conclusions: There has been a marked decrease from 1995 to 1997 in the
ordering of certain diagnostic tests which are seen in advanced HIV. Additionally
there has been dramatic reduction in the # of positive tests in persons with
HIV. HAART and appropriate prophylaxis result in cost savings for diagnostic
laboratory services as well as for other previously defined areas.
S22370 Recent patterns of antiretroviral prescriptions among
HIV-infected patients in care in the United States
Mark S. Dworkin, P.C.T. Wan, J.L. Jones. Centers for Disease Control and
Prevention, Mailstop E-47, 1600 Clifton Road, Atlanta, Georgia, USA
Background: Combination antiretroviral therapy is recommended for many HIVinfected and all AIDS patients.
Methods: Since information on recent patterns of antiretroviral prescriptions for
patients in care reflects actual (not just recommended) practice, we analyzed data
from the Adult and Adolescent Spectrum of HIV Disease Surveillance Initiative
(ASD) to describe the frequency of prescriptions of 1 and not >2 (1T), 2 not
>3 (2T), 3 not >4 (3T), and >4 (>4T) antiretroviral drugs among patients in
care. ASD is a longitudinal medical record surveillance project at inpatient and
outpatient medical facilities in 11 US cities (data from 9 are presented here).
Results: Of 3,648 patients prescribed at least one antiretroviral medication during the most recent 12 months of observation with >6 months observation in 1996
or later (including 2,538 [70%] with AIDS [1993 CDC definition]), 6.3% were prescribed 1T, 41.3% 2T, 43.9% 3T, and 8.5% > 4T. Of patients with AIDS or at least
one viral load of >10,000 during the year of observation (n = 3,105), 5.7% were
prescribed IT, 38.3% 2T, 46.6% 3 T, and 9.4% >4T. The most common prescriptions were zidovudine (ZDV) (46.2%), stavudine (d4T) (19.9%), and didanosine
(12.2%) for patients prescribed 1T (n = 312 prescriptions), ZDV/lamivudine (3tC)
(53.1%), d4T/3tC (25.4%), ZDV/zalcitabine (ddC) (3.5%) for patients prescribed
2T (n = 2,113 prescriptions), and ZDV/3tC/indinavir (20.3%), d4T/3tC/indinavir
(20.3%), ZDV/3tC/saquinavir (10.8%) for patients prescribed 3T (n = 2,417 prescriptions).
Conclusions: Among patients with AIDS or a viral load >10,000, a majority
were prescribed >3 drug therapy but a significant minority were prescribed dual
or monotherapy. Describing this latter group of patients and potential associated
factors is important for future research.

I 22371

A phase II randomized open label study of adefovir
dipivoxil (PreveonT", ADV) in combinations with indinavir
(IDV), zidovudine (ZDV), lamivudine (3TC), and stavudine
(D4T) in therapy naive HIV-infected patients

Dean Winslow1, A. Myers2, G. Blick3, D. Shepp4, G. Simon5, D. Coakley',
J. Lee1. 'GILEAD Sciences, 333 Lakeside Drive, Foster City CA; 2Phoenix Body
Positive, Phoenix, AZ; 3Blick Medical, Stamford, CT; 4North Shore Hospital,
Manhasset, NY; 5GWUMC, Washington, DC, USA
Objective: To describe the immunologic and virologic response of adefovir dipivoxil (ADV) when administered in triple and quadruple combinations with IDV
compared with IDV + ZDV + 3TC.
Methods: The study is a multi-center, open-label study of antiretroviral naive
HIV-infected patients randomized to a) ADV + IDV + ZDV + 3TC b) ADV + IDV
+ ZDV c) ADV + IDV + 3TC d) ADV + IDV + D4T or e) IDV + ZDV + 3TC. ADV
was given as 120 mg qd with 500 mg L-carnitine. As of December 30, 1997,
130 patients had been randomized; preliminary baseline demographics include:
Male 90%, Caucasian 59%, mean duration of HIV-infection 4.4 years, mean age
37 years, mean HIV RNA 5.0 log copies/mL, mean CD4 count 392 cells/mm3.
13 patients (10%) have terminated therapy for reasons including gastrointestinal
intolerance (5), and patient request or non-compliance (5). Grade III or IV or
serious adverse events possibly or probably related to antiretroviral therapy have
been reported in 12% of patients with the most common being reversible asymptomatic elevations of AST, ALT, or CPK. No substantial differences between the
treatment groups were noted. A planned interim analysis reviewing HIV-1 RNA
results following 20 weeks of treatment will be presented.
Conclusions: Adefovir dipivoxil can be safely combined with either ZDV, 3TC,
or D4T in indinavir containing combination regimens over a 20 week period. Long
term safety will be assessed over 48 weeks.
22372 1 Novel double protease combinations-combining indinavir
(IDV) with ritonavir (RTV): Results from first study
Cassy Workman', R. Musson', W. Dyer2, J. Sullivan2. 1Fitzroy Street Centre, 75
Fitzroy Street, Surry Hills, Sydney; 2Australian Red Cross Blood Blank, Sydney,
Australia
Background: Studies have shown IDV to be a potent Protease Inhibitor however
the current dosing regimen requires tid dosing with food restrictions and added
hydration to avoid kidney stones. Pharmacokinetic data indicated that IDV+RTV
may be a promising combination allowing convenient bid dosing with no food
restrictions, less interpatient variability (IDV) and lowered Cmax (IDV) which theoretically could decrease IDV associated nephrolithiasis. This study investigates
the safety, tolerability and efficacy of combining combining IDV and RTV at 400
mg IDV bid given with 400 mg RTV bid.
Method: 24 patients in two groups were initiated on quadruple therapy of IDV
plus RTV+d4T+3TC. Patients were instructed not to increase their fluid intake.
Group A consisted of 12 patients who received quadruple therapy with d4T, 3TC,

RTV and Saquinavir for >6 months previously and who had maintained viral RNA
levels <400 copies/ml for >6 months with stable CD4 counts. Group B consisted
of 12 patients, all treatment naive. As Group A was already receiving d4T, 3TC
and RTV this was considered an ideal group to ascertain specific problems
with IND+RIT. The mean baseline viral load in group B was 65,316 copies/ml
(Amplicor).
Results: In group A: all patients maintained undetectable viral RNA up to 36
weeks; 9/12 experienced substantial CD4 increases after switching therapies
(previously stable). In group B, 10 patients had reached week 12. All had viral
load below 400 copies/ml. 1 patient (group A) discontinued after experiencing
severe cracked lips. 3 patients in group B experienced mild diarrhoea, which
settled without dose change. No nephrolithiasis was noted.
Results to 52 weeks (group A) and 32 weeks (group B) will be presented with
viral load results to <40 copies/ml.
Conclusions: Initial results show the combination of RTV/IND with d4T and
3TC is efficacious and well-tolerated, allowing for convenient BID dosing without
the requirements associated with indinavir therapy. The unexpected increase
in CD4 counts observed in Group A suggests possible benefits from switching
regimens even though viral load results in this group were already previously
below detection. This phenomena warrents further investigation.
S22373 The impact of highly active antiretroviral therapy on
HIV-associated hospital admissions and deaths
Pere Domingo, J.M. Guardiola, J. Ris. Hospital de Sant Pau Internal Medicine
Av Sant Antoni Ma Claret, 167 08025 Barcelona, Spain
Objective: To determine the extent of needs in clinical assitance between two
periods of time with or without the widespread use of highly active antiretroviral
therapy (HAART).
Design: Retrospective study
Methods:The study was carried out in a 750-bed university teaching hospital
in Barcelona, Spain. The hospital serves as a referral centre for adults and is
located in an urban area, serving a population of 620,000. To determine how
HAART has changed the need for hospital care among our HIV-infected patients,
we have examined the records of HIV-infected patients admitted to our hospital
and the cause of admission in the first nine months of 1996 (period I) and 1997
(period II). Prophylaxis against opportunistic infections was done following CDC
guidelines during both periods of the study. During period I protease inhibitors
were not available, whereas they were widely available in period II. Statistical
analyses were performed with the StatView 4.5' statistical package.
Results: From January 1 to September 30, 1996, there were 18374 admissions to our hospital of which 201 (1.09%) occurred in HIV-infected patients. From
January I to June 30, 1997, there were 16979 admissions to our hospital of which
129 (0.76%) occurred in HIV-infected patients (p = 0.001). Only 9 patients (4.5%)
during period I and 7 (5.4%) during period II were newly diagnosed as having HIV
infection during admission (p = 0.89). Both groups of patients were comparable
with respect to age and sex distribution. There were not statistically significant
differences between patients admitted to the hospital in both periods with respect
to the cause of admission. The mean hospital stay of survivors during period I
was 17.1 + 12.4 days (range: 3-72 days), whereas that of survivors during period
II was 14.5 ~ 13.5 days (range: 2-62 days), a 22.5% decrease (p = 0.06). There
were differences between both periods with respect to the relative prevalence
of infections 0, neoplasms (11.9% vs. 3.9%) or miscellaneous causes (14.9%
vs. 19.4%), requiring hospital admission (p = 0.03). There we.e not statistically
significant differences between both periods with respect to the frequency of diagnosis of infectious diseases without effective prophylaxis or neoplasms (58.2%
vs. 54.3%, p = 0.55). The overall case-fatality rate during admission was 26.9%
(54 out of 201) in period I, and 3.1% (4 out of 129) in period II (p = 0.0001). The
potential years of life lost were 1830 during period I and 89 during period II, a
95.1% decrease.
Conclusions: The introduction of new antiretroviral regimes, i.e. HAART, has
substantially changed the need for hospital stay among HIV-infected patients, not
only decreasing the number of admissions but also decreasing the mean stay.
HIV-associated mortality has also significantly decreased after introduction on
highly active antiretroviral treatment which has caused a dramatic reduction in
potential years of life lost.
22374 Decline in mortality rates and opportunistic disease with
combination antiretroviral therapy
Richard Moore', J.C. Keruly2, J. Gallant2, R.E. Chaisson2. 11830 E Monument
St Room 8059 Baltimore Maryland 21205; 2Johns Hopkins University Baltimore
MD, USA
Objectives: To determine the impact of combination antiretroviral therapy
(COMBO) on clinical HIV disease progression.
Methods: We assessed patients who ever had a CD4 < 200 cells/mm3 and
were receiving longitudinal care in a large urban academic HIV specialty practice
in the US (N = 1500). We compared mortality rates and the incidence of oppor
tunistic illness (01) in 1993-95 when antiretroviral monotherapy was the standard
of care with 1996-97 when COMBO was the standard of care.
Results: COMBO was used in 85% of patients in 1996-97 (63% received a
PI) and 9% in 1993-95 (<1% PI use). Compared to 1993-95, use of COMBO
in 1996-97 was associated with a reduction in the mortality rate (-31%) and
in several Ols: cytomegalovirus disease (-80%), cryptosporidiosis (-74%), toxoplasmosis (-71%), M. avium complex disease (-49%), Pneumocystis carinii