Recurrence or Worsening of AIDS-defining Opportunistic Infection (OI)

Recurrence or Worsening of AIDS-defining Opportunistic Infection (OI)

Recurrence or Worsening of AIDS-defining Opportunistic Infection (OI) due to Immune Reconstitution Inflammatory Syndrome (IRIS)
During Initial HAART Among a Clinic-Based Population
Poster #H-2332

Harborview Medical Center
325 9th Avenue, Box 359931
Seattle, WA, 98121
206-744-3631
[email protected]

Achenbach C and Kitahata M -- University of Washington, Seattle, WA, USA

Methods
Study type: Single center retrospective observational study conducted
among all patients in the University of Washington HIV Cohort
Patients Included:
18 years of age with CDC AIDS-defining illness
Non-infectious (wasting, dementia, lymphoma, cervical CA) and
chronic or recurrent infections difficult to classify as IRIS (recurrent
pneumonia, chronic HSV ulcer, salmonella septicemia) were excluded
OI stable or improving prior to initiation of first HAART
1 log copies/ml decline in HIV viral load
Recurrence or Worsening of OI Assessment:
During the first 12 months of HAART, records for every patient were
reviewed for recurrent or worsening signs or symptoms of prior OI
Definition of IRIS: Recurrence or worsening of OI with an atypical
inflammatory reaction based on examination, radiography, and/or
laboratory results
Statistical analyses: We performed univariate comparisons of
demographic and clinical characteristics between patients with and
without IRIS using Chi-square and Wilcoxon rank sums. Comparisons were
also made between those with recurrence or worsening due to IRIS versus
other reasons
Results

201 patients with 272 prior OIs initiated HAART between 1/96 and
12/07 (Tables 1 and 2)
Median time from OI diagnosis to HAART initiation was 2.7 months
(range 0-50)

Table 1. Demographic and clinical characteristics overall and of patients with and
without IRIS
Characteristic

Overall
(N=201)
N (%)

IRIS
(N=29)
N (%)

No-IRIS
(N=172)
N (%)

P-value

84 (42)
117 (58)

13 (45)
26 (55)

71 (41)
101 (59)

0.72

Male
Female

175 (87)
26 (13)

26 (90)
3 (10)

149 (87)
23 (13)

0.65

135 (67)
66 (33)

20 (69)
9 (31)

115 (67)
57 (33)

0.82

Among IRIS patients, 10 (34%) were hospitalized, 6 (21%) had
persistent symptoms and 2 (7%) died

Race
White
Non-white
HIV transmission risk factor
IDU
Other

57 (28)
144 (72)

7 (24)
22 (76)

50 (29)
122 (71)

0.59

CD4+ cell count nadir (cells/mm3)
<50 50 127 (63) 74 (37) 16 (55) 13 (45) 111 (65) 61 (35) 0.33 HAART started NNRTI PI Boosted PI PI + NNRTI 63 (31) 60 (30) 56 (28) 22 (11) 9 (31) 6 (21) 13 (45) 1 (3) 54 (31) 54 (31) 43 (25) 21 (12) 0.10 56 (28) 145 (72) 13 (45) 16 (55) 43 (25) 129 (75) 0.03 89 (44) 112 (56) 15 (52) 14 (48) Table 2. OIs diagnosed prior to HAART initiation OI N (%) PCP Candida esophagitis KS (visceral) KS (mucocutaneous) TB CMV Cryptosporidiosis MAC Toxoplasmosis Cryptococcus HSV esophagitis PML Histoplasmosis Isosporiasis 74 (27) 64 (24) 7 (2) 35 (13) 28 (10) 16 (7) 14 (5) 12 (4) 9 (3) 7 (2) 2 (1) 2 (1) 1 (0.5) 1 (0.5) Both deaths had KS (one visceral and one MC) and 4/6 (66%) of persistent disease had MC KS 17/201 (8.5%) patients had another reason for recurrence or worsening (Table 3): 8 with new different infection and 9 with usual recurrence of OI (absence of atypical inflammatory reaction) Characteristic IRIS (N=29) N (%) Other (N=17) N (%) P-value 74 (43) 98 (57) 0.38 KS (mucocutaneous) KS (visceral) TB MAC PCP CMV Candida Esophagitis Cryptococcus Cryptosporidiosis 12 (40) 2 (7) 5 (17) 3 (10) 4 (14) 1 (4) 1 (4) 1 (4) 0 (0) 0 (0) 0 (0) 1 (6) 1 (6) 5 (29) 0 (0) 7 (41) 1 (6) 2 (12) 0.001 16 (55) 13 (45) 13 (76) 4 (24) 0.14 9 (31) 20 (69) 10 (59) 7 (41) 0.06 0 (0) 17 (100) 0.03 Event Duration (days) <60 60 On OI treatment at HAART initiation Yes No CD4+ cell count nadir (cells/mm3) <50 50 Time from HAART initiation to IRIS (days) OI Diagnoses Time from OI diagnosis to HAART initiation (days) <60 60 Hospitalization during IRIS was greatest for those with PCP (3/4, 75%) and TB (3/5, 60%) Table 3. Comparison of clinical characteristics between those with recurrence or worsening due to IRIS versus other reasons Boosted PI-based HAART Yes No 23/29 (79%) of IRIS events in 6 months (Figure) IRIS was most frequent in patients with KS (14/42, 34%), MAC (3/12, 25%), TB (5/28, 18%), and Cryptococcus (1/7, 14%) (Tables 2 and 3) Sex Figure. IRIS events per OI and time from HAART initiation to event Recurrence or worsening occurred in 46/201 (23%) of patients with 29/201 (14%) due to IRIS Median time from initiation of HAART to IRIS was 10 weeks (range 0.7 56) Age <45 45 Results (cont.) OI Recurrence or Worsening on HAART Percentage of IRIS Events Background There is uncertainty regarding the frequency, predictors, and outcomes of IRIS events Prior studies on IRIS have been limited to convenience samples of selected OIs (usually TB, MAC, and/or cryptococcus) We explored IRIS, in a clinic population, among all patients with any prior OI who were started their first HAART regimen 7 (24) 22 (76) Summary of Results 14% of all patients with a prior OI experienced IRIS on their first HAART regimen The majority of IRIS events occurred early in HAART (< 6 months) for all diagnoses One-third of IRIS events led to severe disease requiring hospitalization KS-IRIS was notable for the following: 1/3 of cases occurred late in HAART treatment Led to 2/2 deaths and 2/3 of persistent disease A greater proportion of IRIS patients were treated with boosted PI-based HAART regimens Conclusions In a clinic population of all patients with OIs who initiated HAART, we observed IRIS to be a severe condition leading to hospitalization and, occasionally, death The type of HAART used and resulting dynamics of HIV suppression or immunologic reactivation are likely important factors for the development of IRIS Further investigation of immunologic markers prior to IRIS might help predict this serious syndrome

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