Systematic Review and Meta-Analysis of Secondary

Prophylaxis for Prevention

of HIV-related Toxoplasmic Encephalitis Relapse
Using Trimethoprim-sulfamethoxazole

Presented By:
dr. Ahmad Syaukat

Supervisor:
dr. Andika Okparasta, Sp.S(K)

Neurology Department
Medical Faculty Of Universitas Sriwijaya
Dr. Mohammad Hoesin General Hospital Palembang
2022
 Journal Reading
Available at Pathogens and Global Health
 BACKGROUND
Systematic literature and • There is a relative efficacy of TMP-SMX for the
meta-analysis by treatment of toxoplasmic encephalitis in
Hernandez et al. patients with AIDS

The aim of this study was to conduct a systematic literature

review and meta-analysis to estimate relapse rates associated
with TMP-SMX in secondary prophylaxis following
improvement of an episode of TE.
 02
METHODS
 Search strategy

Guideline used
PRISMA

Database Study eligibility

PubMed, Embase, and Assessed by two independent
CENTRAL reviewers
 Search Strategy
Inclusion : Exclusion :

• Studies with data findings on patients • Studies in primary prophylaxis

with HIV infection or AIDS, receiving • Review articles, letters to the editor,
secondary prophylaxis with TMP-SMX comments, case reports, and
after resolution of a prior TE event. preclinical studies
• Studies that reported relapse
outcomes during maintenance
treatment
• Published in peer-reviewed journals
• English, Spanish, Portuguese, German
or French.
 Data extraction
Extracted • First author, publication year, study design,
demographics, acute and maintenance treatment
data regimens, number of patients evaluated for relapse,
included: incidence of relapse, and time of follow-up.

Meta- • Consisted of six studies representing 235 patients

analysis receiving TMP-SMX as a secondary prophylaxis for TE
 Quality assessment
The quality assessment tools from the National Heart,
Lung, and Blood Institute of the NIH for quality
assessment of Observational Cohort and Cross-
Sectional Studies and Controlled Intervention
were used to assess the quality of included studies
 Statistical analyses
The primary outcome →
The estimate of
Rate of relapse Relapse rates were
heterogeneity was
associated with TMP- transformed using the
quantified by the I2
SMX maintenance Freeman-Tukey method
consistency score.
therapy.

The data was pooled The analysis was

using both fixed-effect performed using
and random-effects StatsDirect statistical
meta-analysis models. program version 2.8.0
 03
RESULTS
 Characteristics of studies
6 were extracted
663 were excluded
38 were excluded for this study (1
based on abstract
707 initial because it didn’t RCT, 4 prospective
screening &
identified study meet inclusion cohort & 1
removal of
criteria retrospective
duplicates
cohort

• No substantial differences were found in administered doses of TMP-SMX

for both the acute and maintenance treatment phase across studies, except
for Chaddha et al.
• The follow-up for pre-HAART studies was considerably shorter than the
follow up forpost-HAART
Quality
assesment
• The quality of 6 studies was
rated as fair, with a risk of
bias due to lack of blinding,
• This condidered sufficient
qualityto be included in the
meta-analysis.
 Meta-analyses
The combined TMP-SMX relapse rate was 16.4% (95%CI = 6.2% to 30.3%) using a
random-effects models.

In a sub analysis in which only the pre-HAART studies (n = 4) were included, the
relapse rate was 14.9% (random effects; 95% CI = 3.7% to 31.9%) with I2 = 79.4%
(95% CI = 11.7% to 90.4%).

Analysis of two post-HAART studies indicated a relapse rate of 19.2% (random

effects; 95% CI = 2.8% to 45.6%), I2 values unassessable due to limited number of
studies (n = 2)
Forest Plot from the combined analysis of pre- and post-HAART studies
 TMP-SMX maintenance therapy relapse rates based on
proportions meta-analysis for aggregate Pre- and Post-HAART
and individual HAART periods
 04
DISCUSSION
Pyrimethamine plus sulfadiazine is the preferred
regimen in secondary prophylaxis and
pyrimethamine plus clindamycin is the preferred
second-line treatment in most guidelines.
TMP-SMX and other antibiotic alone and in
combination are listed as alternative regimens.
 A previous
This study
investigation
• This might reflecting the licensed
indication of pyrimethamine for the
Regiment Regiment
relapse rates of relapse rate of treatment of toxoplasmosis.
19.2% 16.2% • This results use independent
proportions test so we can’t directly
Fixed effect
Identified data compare the rates of relapse
of six studies
models of
including 235
11.1%
patients
 This study showed
In that pre-HAART large heterogeneity
On this basis the
relapse rates were and a limited
random effect
not observed to be number of post-
results were
higher than the HAART evaluations
presented
post-HAART using TMP-SMX
(n = 100)

Poor adherence to TMP-SMX secondary prophylaxis seem to be

the most probable cause of TE relapse.
 • A wide range of study designs to reflect real-world outcomes for the
management of secondary prophylaxis
Strength: • Adding dimension to the results reported by Hernandez.,
• Informing relapse rates for TMP-SMX

Limitations: • Cautious interpretation is necessary due to the heterogeneity observed.

Future • Larger randomized clinical trials are important to obtain a conclusive

answer regarding relapse rates associated with TMP-SMX for secondary
studies: prophylaxis of HIV-related TE.
THANK YOU
Any questions?