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

296 Abstracts 22170-22174

12th World AIDS Conference

Results: 86 isolates (84 blood, 2 bone marrow) from 76 pts (65 men, 11
women; mean age 37; median CD4 10) were tested. Resistance incidence (%):
AM 9.3, CI 41.9, CR 27.9, CF 17.4, ET 3.5, RF 30.2. Resistance was present to
_-1 drug in 64 (74.4%) and >2 drugs in 26 (30.2%) isolates. Frequency (n, %)
of clinical circumstances for 74 (86%) isolates: B 21 (28.4), F 12 (16.2), RL 7
(9.5), NI 34 (45.9). Clarithromycin resistance was associated with clarithromycin
prophylaxis (p = 0.002). Rifabutin resistance trended with rifabutin prophylaxis (p
= 0.08). Frequency (n, %) of response for 62 (72%) isolates: R 29 (46.8), TF 13
(21.0), D 20 (32.2). The median follow up was 112 days. There was no association between resistance to any single agent and response (p = NS). Multivariate
logistic regression yielded odds ratios for resolution of DMAC for these factors:
CD4 count 1.01, greater than 2 active drugs (no resistance present) in regimen
1.42, combination antiretroviral therapy (nucleoside or protease inhibitor) 2.28,
and use of clofazimine in regimen 0.52.
Conclusions: Clinical resolution of DMAC in AIDS pts correlates with interpretations of drug susceptibility. Multi-drug resistant strains of MAC were commonly
observed. Development of CR resistance in vitro correlated to breakthrough on
CR prophylaxis in vivo. Despite the presence of drug resistance, treatment could
be successful with active anti-MAC agents when their susceptibility was known.
22170 Liposomal amikacin (LA) for the treatment of
non-tuberculous mycobacteria (NTM) in HIV disease
Mark Nelson, C. Richardson, B.S. Gazzard. Chelsea and Westminster Hospital,
369 Fulman RD, London, England, UK
Aim: To describe the use of LA (MiKasome-Nexstar Pharmaceuticals) in the
treatment of NTM.
Methods: Individuals failing or intolerant of standard anti NTM therapy were
eligible for treatment with LA. LA was infused intravenously at a dose of 20
mg/kg on alternate days for 2 weeks, followed by a fortnightly maintenance
therapy at the same dose.
Results: 9 patients have received LA for this indication - 8 for MAC/1 for M.
kansasii. One patient failed to re-attend after 3 doses and subsequently died,
one patient developed renal failure and one an anaphylactic reaction to LA. Of
the remaining 6, 5 responded microbiologically (conversion to negative blood
culture) and all 6 clinically to LA. All received maintenance therapy - one died 2
months later, secondary to non-mycobacterial disease, and one elected to stop
maintenance therapy after 6 months, and remains disease free 6 months later.
The remaining 4 all relapsed 0.5-5 months post induction. All were subsequently
successfully re-induced (3) at doses between 30-40 mg/kg 1 alternate days; or
had their maintenance therapy increased to 30 mg/kg 1 (1). One other patient
developed renal failure on LA, but this responded to cessation of NSAID drugs.
No other toxicities were noted.
Conclusion: NTM is a serious condition in HIV disease with few available
treatments. LA was successful in treating 6/9 patients with NTM, with one patient failing to re-attend, and one each developing anaphyloxis and renal failure.
When used as maintenance treatment relapse is common, but individuals may
be successfully re-induced at higher doses.
| 22171 Skin test reactivity to Mycobacterium avium sensitin
(MAS) in HIV+ persons with and without disseminated
MAC and highly active antiretroviral therapy (HAART)
Lorraine Alexander1, C.R. Horsburgh, Jr.1, J.L. Lennox1, C.F. von Reyn2.
1Emory University School of Medicine 69 Butler Street Atlanta GA 30303;
2 Dartmouth College Hanover, NH, USA
Objectives: to determine if anergic HIV+ persons whose CD4 counts rise with
HAART recover previous delayed-type hypersensitivity (DTH) and/or acquire DTH
to mycobacterial antigens after an episode of disseminated M. avium complex
(DMAC) or tuberculosis (TB).
Design: Cross-sectional study.
Methods: Patients were identified at an urban HIV clinic in the southeastern
US. DMAC was defined as isolation of MAC from blood. HAART+ were defined
as persons whose CD4 count had been below 50 cells/mm3 and was now >100
cells/mm3 on therapy. HAART- were persons not on HAART and having less
than 50 CD4 cells/mm3. Controls were HIV+ persons with similar demographic
characteristics. Dual skin testing was performed with PPD and MAS. PPD+ was
>5 mm in HIV+ and >10 mm in HIV-; MAS dominant reaction was >5 mm with a
contemporaneous PPD reaction at least 5 mm smaller than the MAS.
Results:

22172 1 Manifestation of mycobacterial infection after initiating of
highly active antiretroviral therapy (HAART)
Christian Hoffmann1, H.A. Horst', 0. Degen2, J. Van Lunzen2, H.J. Stellbrink2
'HIV-Ambulanz in Staedt, Krankenhause Kiel, Chemnitzstrasse; 2 Med
Kern/Poliklinik, Univ. of Hamburg, Geramy
Objectives: Initiating of HAART results in dramatic decreases in HIV viral load
(VL) with concomitant restoration of cell mediated immune function. However, this
may lead to a marked inflammatory reaction and to altered clinical manifestations
of preexisting latent infections.
Design/Methods: A retrospective analysis identified 5 pts. (4 males) with mycobacterial lymphadenitis (ML) during the first 8 weeks after initiating of HAART.
ML was defined as adenopathy with detection of acid-fast bacilli (AFB) and/or
histologically caseous necrosis and granuloma (CNG).
Results: Median CD4+-count of the 5 pts. was 25 cells/pl, and median VL
was 102.250 RNA copies/ml. 4/5 pts. were naive to antiretroviral therapy. ML
occurred within 10 to 54 days after initiating of HAART. At this time, all pts.
showed fever, weakness and splenomegaly, and 4/5 pts. developed anemia with
Hb <10 g/dl. Adenopathy was cervical (3/5), submandibular (2/5), mediastinal
(3/5), and preauricular (1/5). One pt. showed severe hemophagocytic syndrome
which was confirmed by bone marrow biopsy. As of 1998, all pts. are alive and 4/5
show substantial clinical improvement after start of anti-mycobacterial therapy.

Pt. HAART CD4+-increase VL-decrease

Histological confirmation

M/60 AZT/3TC/SQV
M/56 AZT/3TC/SQV
M/53 AZT/ddC/NLF
W/44 d4T/3TC/IDV
M/52 AZT/3TC/NLF

22-160
12-239
119-NA
150-224
25.82

32.500- -25 M. genavense (submandibular)
150.000 -1.200 AFB, not classifiable (submandibular)
54.500-NA CNG (spleen)
NA-50 M. avium (mediastinal)
365.000- -400 M. tuberculosis (mediastinal)

Suspected
Conclusion: Mycobacterial infection after initiation of HAART may represent
an activation of the disease with a subsequent tissue suppuration and granuloma
formation due to a marked T-cell or macrophage-mediated and antigen-specific
inflammatory reaction. Therefore, patients with severe immune dysfunction should
be monitored very carefully, in particular during the first weeks after initiating of
HAART.
[22173 Is a response to amikacin therapy predictive of MAC
infection?
Ann Sullivan, M. Hannan, B. Azadian, M. Nelson, B. Gazzard. St Stephensen
Centre, Chelsea and Westminister Hospital, 369 Fulham Rd, London, SW10
9NH, England
Objectives: 1. To examine the role of amikacin in the management of presumptive MAC infection. 2. To identify factors predictive of subsequent isolation of
mycobacteria and, in particular, to determine if clinical response to amikacin
therapy was a predictor of disease.
Design: Retrospective case note review
Methods: All HIV-1 positive patients who received intravenous amikacin therapy for a presumptive diagnosis of MAC between October 1994 and September
1997 were included. 4 patients were excluded on the basis of an alternative
diagnosis. The case notes and computer data base were reviewed. Clinical presentation, laboratory results, drug therapy and response to amikacin therapy were
recorded.
Results: 65 patients received amikacin for presumptive MAC infection of
whom 17 were subsequently proven to have nontuberculous mycobacterial infection (NTM). 61 were men and 4 were women. Mean age was 37.8 years. Patients
with NTM infection had a lower CD4 cell count than those with no causative
organism found (median CD4 5 vs 16 cell/ml p = 0.01). A similar percentage
in both groups had AIDS (88 vs 90%). There were no differences in clinical
presentation or laboratory results. A similar percentage in each group responded
to treatment (81 vs 63%) and became afebrile on therapy (60 vs 50%), although
the afebrile response time showed a trend to being longer for the NTM group
(7.4 vs 4.3 days, p = 0.07). Of those patients whose pre-treatment culture was
positive 12 (71%) had subsequent negative cultures. The survival for both groups
was the same (1 yr).
Conclusion: In patients with a clinical picture consistent with MAC infection
response to amikacin therapy was similar irrespective of whether MAC infection
was subsequently proven. Although clinical response to amikacin therapy cannot
be used to predict subsequent MAC isolation it does produce a good clinical
outcome. Response to therapy should not result in commencement of long term
oral anti-MAC therapy unless confirmed by blood culture.
22174] Mycobacterium avium intracellulare complex infection in
HIV-infected children
Anna Maccabruni1, D. Caselli2, L. Arlandi3, I. Pacati3, B. Castiglioni3,
G. Michelone3. 1Pavia Policlinico S. Matteo Institute of Infectious Diseases Via
Taramelli 5; 2Pediatric Department Policlinico S. Matteo Pavia; 3lnstitute of
Infectious Diseases University of Pavia, Italy
Infection with nontuberculous mycobacteria included in Mycobacterium avium
complex (MAC) has been reported with increasing frequency among adult and
pediatric patients with HIV infection. Advanced HIV-related immunodeficiency is

Group
DMAC, HAART
DMAC+, HAART+
DMAC, HAART+
TB+, HAART+
Controls

MAS dom/Total (%)
0/39 (0%)
6/10 (60%)
4/11 (36%)
0/3 (0%)
51/134 (38%)

PPD+/total (%)
0/39 (0%)
0/10 (0%)
4/11 (36%)
1/3 (33%)
17/134 (13%)

p - 0.001 p < 0.02
Conclusion: These results suggest that rises in CD4 counts after HAART
result in restoration of DTH to mycobacterial antigens to the degree that would
have been expected before HIV-induced anergy. However, at least some persons
with TB or DMAC did not acquire DTH to organisms with which they had been
infected.