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

40 Abstracts 12144-12147

12th World AIDS Conference

Method: Prospective cohort of HIV-1-infected adults enrolled at an AIDS
support organisation (TASO) clinic in Entebbe, Uganda, from October 1995 to
December 1997.
Results: 1,201 HIV-1-infected patients have been followed for 1,171 patient
years. Median follow-up 10.9 months. Mortality was 24% per year; by CD4+T-cell
count at enrolment number/uL: > 500 - 3.2%, 200-500 - 8.7%, < 200 - 55.2%
(median survival 14.7 months). The number and principal causes of death by
CD4 T-cell count group were: CD4 > 500, 10 deaths - acute respiratory disease
20%, non HIV related 20%, unknown cause 20%; CD4 200-500 36 deaths -
chronic febrile syndrome/wasting 15%, acute respiratory disease 15%, kaposi's
sarcoma 9%, Tuberculosis 9%, unknown 12%, CD4 < 200 226 deaths - chronic
febrile syndrome/wasting 39%, Cryptococcal meningitis 11%, Kaposi's sarcoma
5%, Tuberculosis 3%, Cryptosporidium 2%, Non-HIV 2% and Unknown 7%. 26
recruits could not be grouped by CD4 count in which 12 deaths took place,
Cryptococcus in 33%, Chronic fever/wasting 33%, unknown 17%.
Conclusion: Mortality rates in HIV-1-infected Ugandans are high and CD4
related. Survival times are similar to those reported from North America in the
1980's. Improvements in infection prophylaxis and antiretrovirals will be crucial
in Africa if survival is to be improved. Mycobacterial and bacterial infections are
common in this cohort, but account for small numbers of deaths. Access to clinical
services for recognition and treatment of these conditions must be a priority.
S12144 1 Clinical and immunologic spectrum of disease among
2261 HIV-1-infected patients at a hospital in Bangkok
Pauli Amornkul', S. Tansuphasawadikul2, K. Limpakarnjanarat3,
J. Kaewkungwal3, S. Likanonsakul3, B. Eampokalap2, T Naiwatanakul3.
1CDC/DHAP 1600 Clifton Road, MS E-50, Atlanta, GA 30333, USA;
2Bamrasnaradura Infectious Disease Hosp., Bangkok; 3HIV/AIDS Collaboration,
Bangkok, Thailand
Background: The clinical spectrum of HIV infection, effect of opportunistic infections (Ols), and differences in pathogenesis associated with HIV-1 subtypes
have been incompletely defined in Asia. Such information is critical in improving
the lives of HIV-infected persons in Asia through preventive, therapeutic, and
eventual vaccine interventions. We describe the clinical and immunologic presentations, including differences by subtype, of HIV-1-seropositive patients on their
first admission to a hospital in Bangkok.
Methods: From 11/93 through 6/96, inpatients (>14 years) at an infectious
disease hospital received HIV counseling and testing. Demographic, clinical, and
laboratory data were collected by enhanced surveillance.
Results: Of 10,876 admitted patients, 2261 (20.8%) were found to be HIV-positive. Of these, 1926 (85.2%) were male, 1942 (85.9%) were infected sexually
or by non-drug-related means, 319 (14.1%) were injecting drug users (IDUs),
and 1491 (65.9%) had AIDS. The most common AIDS-defining conditions were
extrapulmonary cryptococcosis (EPC) (40.0%), tuberculosis (TB) (39.0%), and
wasting syndrome (WS) (8.5%). IDUs were more likely (p < 0.05) to have TB and
WS but less likely (p < 0.05) to have EPC and Pneumocystis carinii pneumonia.
Lymphocyte counts were measured in 2047 (90.5%) patients; 81.8% had <1500
lymphocytes/LtL. HIV-1 subtype was determined for 2116 (93.6%) patients; 86.5%
had subtype E, and 13.5% had B. Among sexually infected patients, 1734 (95.3%)
had subtype E, and 86 (4.7%) had B. Among IDUs, 199 (67.2%) had subtype
B, and 97 (32.8%) had E. We compared patients with subtype B and those with
E for differences in principal Ols, lymphocyte count, and, when available, CD4
counts by using multivariate analysis controlled for sex and age, for all patients
and for IDUs only. The only difference between subtypes was that E was more
associated with EPC (odds ratio = 2.5; 95% confidence interval, 1.40-4.43).
Conclusion: In the HIV-infected Bangkok population studied, the frequencies
of Ols for IDUs and non-IDUs differed. However, contrary to preliminary results,
HIV-1 subtypes B and E seem to be associated with similar degrees of immune
suppression and, with one exception, with similar 01 patterns.
12145 1 Activity of soft gelatin capsule formulation of saquinavir
in combination with two nucleosides in treatment-naive
HIV-1-seropositive persons
Melanie Thompson. On behalf of the NV15355 study team; ARCA, Atlanta,
Georgia, USA
Background: A soft gelatin capsule formulation of saquinavir (SQV-SGC,
FortovaseM) has been developed which, at a dose of 1.2 g three times daily,
achieves plasma saquinavir (SQV) levels around 8-fold higher than those attained with the saquinavir hard gelatin capsule (SQV-HGC, Invirase~).
Objective: To compare the antiviral activity and safety of SQV-SGC with that
of SQV-HGC.
Methods: 171 antiretroviral-naive HIV-infected patients with plasma HIV-RNA
> 5000 copies/mL were randomized to receive SQV-HGC 600 mg tid (n = 81) or
SQV-SGC 1200 mg tid (n = 90), each in combination with 2 nucleoside reverse
transcriptase inhibitors (nRTIs) of choice. After 16 weeks, patients continued
on the SQV formulation of choice for the study duration (48 weeks + 24-week

extension). Post 16-week data are therefore presented for the SGC arm only.
Results: The mean baseline CD4 counts for the SQV-SGC and SQV-HGC
arms were 448 and 401 cells/mm3, respectively, and both groups had a mean
baseline HIV-RNA of 4.8 copies/mL. At week 16, subjects with HIV-RNA < 400
copies/mL (Amplicor") numbered 80% in the SQV-SGC group and 43% in the
SQV-HGC group (p = 0.001), while those with <50 copies/mL (UltraSensitive)
numbered 46% and 28%, respectively. At that time-point, the mean HIV-RNA

decrease from baseline (using UltraSensitive assay for values <400 copies/mL)
was 2.5 loglo copies/mL for the SQV-SGC group and 1.8 loglo copies/mL for the
SQV-HGC group. In subjects initially randomized to SQV-SGC studied through to
week 40 (n = 58), preliminary data indicate maintenance of HIV-RNA reduction
(mean of 2.7 logio copies/mL from baseline), with 83% at <400 copies/mL and
75% at <50 copies/mL. CD4 counts increased by a mean of 174 cells/mm3 in this
group over the 40-week treatment period. Treatment was generally well tolerated.
The most frequently reported adverse events (AEs) associated with SQV-SGC
were gastrointestinal.
Conclusions: The combination of SQV-SGC 1200 mg tid plus 2 nRTIs provides durable and potent HIV suppression. In the comparative phase of the trial,
the degree of viral suppression with the SGC-based regimen was significantly
greater than that attained with the conventional SQV-HGC formulation. Both formulations of SQV were well tolerated, although the incidence of gastrointestinal
AEs appeared greater in the SQV-SGC group. Patients continue to be followed
and 48-week data will be presented.
S121461 Clinical manifestations of advanced HIV disease using
hospital surveillance, clinical and autopsy data in
Abidjan, C6te d'lvoire
Alan E. Greenberg1"2, A. Kadio3, A.D. Grant4, S.B. Lucas5, G. Djomand6,
S. Kassim6, A. Yapi3, M. Honde3, O. Tossou6, S.Z. Wiktor2, K.M. de Cock2. 101
BP 1712 Abidjan 01; 3Centre Hospitalier Universitaire Iretreichvi Abidjan;
6Project Retro - CI Abidjan, Cote d'lvoire; 2Centers for Disease Control &
Prevention Atlanta GA, USA; 4London School of Hygiene & Tropical Medicine
London; 5UMDS, St. Thomas' Hospital London, UK
Objective: To describe the clinical manifestations of HIV-1 and HIV-2 infections
among hospitalized patients in Abidjan, C6te d'lvoire, and to compare the spectrum of severe HIV-related disease by HIV serostatus, gender, and age group.
Methods: We analyzed data that had been collected via three independent
mechanisms among HIV-infected adults at the two principal university hospitals
of Abidjan between 1991 and 1996: 1) AIDS case surveillance data collected on
2,234 patients from 3/94 to 12/96; 2) clinical studies of 349 patients admitted to
the Infectious Diseases and Pulmonary Medicine Services during two 3-month
periods from 3/95 to 3/96; and 3) an autopsy study conducted on 261 adults dying
on various services in 1991-1992.
Results: In the surveillance database, in which clinical diagnoses were largely
made based on history and physical examinations upon admission to hospital, the
wasting syndrome (66%), tuberculosis (15%), esophageal candidiasis (13%), and
pneumonia (11%) were the most common AIDS-defining diagnoses. In the clinical
and autopsy studies that included more thorough laboratory-based evaluations,
the most frequent diagnoses were tuberculosis (29% and 37%, respectively),
septicemia (18% and 16%), meningitis (10% and 12%), pneumonia (6% and
29%), and cerebral toxoplasmosis (6% and 18%). Strikingly few differences in the
spectrum of disease were found by HIV serostatus, gender, or age group.
Conclusions: These data provide a comprehensive overview of the spectrum
of severe HIV-1- and HIV-2- related disease in West Africa. Although the wasting
syndrome is the most clinically apparent manifestation of severe HIV disease,
more thorough evaluations demonstrate that bacterial infections, tuberculosis and
toxoplasmosis are the most important causes of HIV-related morbidity and mortality in this setting. Lastly, the spectrum of HIV-related disease does not appear
to differ appreciably in various subpopulations.
121471 Immune activation in HIV-infected African individuals:
Immunologic, phenotypic and virologic analyses
Silvia Declich', Guiliano Rizzardini2, M. Lukwiya,6, M. Fabiani3, P. Ferrante4,
C. Ble6, M. Clerici5. 'Lab. Epidemiologia 1st Sup. Sanita Viale Regina Elena
266 Roma; 21 Div. Malattie Infettive H.L. Sacco Milano; 3Lab. Epidemiologia 1st
Sup. Sanita Roma; 4Cattedra Virologia Don C. Gnocchi Foun. Milano; 5Cattedra
Imunologia, Italy; 6St. Mary's Hospital Lacor Gulu, Uganda
Objective: To analyze Immunologic and virologic parameter in fresh peripheral
blood mononuclear cells of HIV-infected African patients living in rural Africa, and
to compare them to those of Italian patients
Methods: African and Italian patients were choosen to be comparable for
the following parameters: disease stage (advanced); CD4 and CD8 counts, sex,
and age. Both functional (antigen- and mitogen-stimulated cytokine production)
and phenotypic (activation markers; apoptosis markers; markers preferentially
expressed by TH1 or TH2 cells or by memory and naive cells) analyses were
performed. HIV plasma viremia was analyzed by competitive polymerase chain
reaction (PCR) and branched DNA techniques.
Results: 1) mitogen-stimulated interferon gamma (IFNy) and tumor necrosis
factor alpha (TNFa) production as well as env peptide-stimulated IFNy, TNFa,
and interleukin 10 (IL-10) production are increased in African HIV infection; 2)
the expression of activation (DR; CD38), TH2-associated (CD7-), and apoptosis
markers (CD95) is significantly augmented in African HIV infection as is the
memory/naive ratio; and 3) plasma viremia is reduced in African compared to

Italian HIV-infected individuals.
Conclusions: results of our analyses, which are the first to be performed on
fresh material from African HIV-infected patients living in Africa, underline that a
score of differences exist when HIV infection in Africa and Europe is compared.
These differences, summarized as abnormal and exaggerated immune activation;
an imbalance in the equilibrium between mechanisms supporting and favoring
AICD, and probably reduced plasma HIV viral load, confirm that in African HIV