Cotrimoxazole prophylaxis reduces death rate by almost 60% in adults taking ART in low and middle-income countries

Cotrimoxazole significantly
reduces death among adults on ART in low and middle-income countries, according to a systematic review and
meta-analysis published in the October online edition of the Bulletin of the World Health Organization.

Pooled analysis of seven
studies showed that cotrimoxazole prophylaxis reduced the incidence of death by
close to 60% (0.42, 95% CI: 0.29-0.61).

However, further research is
needed to determine the optimum length of time for cotrimoxazole treatment in
HIV-infected adults on ART. An on-going
randomised double-blind placebo controlled trial involving 2000 individuals in
Uganda is looking at this question, with results anticipated in 2014.

These findings together with those
from a recent cost-effectiveness model lend further support to the World Health
Organization’s (WHO) recommendations to scale up the use of cotrimoxazole in
HIV-infected individuals starting or on ART.

Widespread implementation
will importantly help reduce the high early death rate among HIV-infected
individuals in low- and middle-income countries.

Those in low-income countries
present at a more advanced stage of illness compared to those in high-income
countries. Yet even when adjusting for differences in CD4 cell count at
baseline death in the first few months remains higher among those in low-income
countries. 

Cotrimoxazole is a cheap ($7
for each patient per year), widely available antibiotic, easy to use with no
adverse side effects. Studies have suggested it is effective against common
causes of death and risks of disease including malaria in people with HIV
regardless of whether they are on ART or not.

Common causes of death among
those on ART in low- and middle-income countries include sepsis, tuberculosis,
meningitis, encephalitis, PCP, Kaposi’s sarcoma and diarrhoea.

Cotrimoxazole is a
potentially important intervention in helping reduce the high early death rate
of those starting or on ART.

In high-income countries it
is given to those who present late for care primarily to prevent pneumocystis
jirovecii (carinii) pneumonia (PCP). It is used in low- and middle-income
countries for a wide range of bacterial and fungal infections and is not
limited to those with advanced HIV.

.

WHO recommends its use in
adults with WHO HIV clinical stage 2, 3 or 4 in settings with a limited health care
infrastructure. Where HIV prevalence is high, however, the recommendation is
for all HIV-infected adults to be treated since it reduces disease regardless
of disease stage or CD4 cell count and makes distribution easier.

The authors undertook a systematic
review of the effect of daily cotrimoxazole prophylaxis on death and disease in
people on ART aged 13 or over.

In December 2010 they
searched PubMed and Embase databases for randomised controlled trials and
prospective and retrospective cohort studies comparing death and disease in
HIV-infected individuals on cotrimoxazole and ART and on ART alone.

Selection, confounding and measurement
bias was assessed. There was no evidence of publication bias.

Significant increased
survival was seen when cotrimoxazole was continued at the start of ART, was
begun at the same time as when ART was started or when starting cotrimoxazole
when the patient was stable on ART.

Despite cotrimoxazole being
widely available, cheap, safe and effective in helping reduce the high early
death rate among people with HIV in low- and middle-income countries, its use
remains limited.

The authors suggest reasons
include: delays in the dissemination of the recommendations for its use; drug
procurement and supply problems; poor health care infrastructure for managing
patients before ART as well as inadequate monitoring and evaluation.

They suggest in addition to
resolving these issues getting more adults on cotrimoxazole can be achieved by
making its benefits known and using indicators to monitor its use globally and
at the individual treatment programme level.

The authors highlight WHO’s
priority (with UNAIDS) outlined in the Treatment 2.0 initiative of identifying,
retaining and caring for people earlier in the course of HIV infection to
improve both clinical and programme outcomes. They note currently over 50% of
people are lost to care between diagnosis and starting ART.

They propose that providing
free cotrimoxazole could help keep people in care and look at the individual’s
ability to adhere to treatment as well as improve the survival of those not on
ART.

Reduced early death rates as
well as better retention could be further improved if intensified tuberculosis
case-finding took place at every health visit and isoniazid given to those with
tuberculosis without a cough, night sweats, weight loss or fever, the authors
add.

Limitations include most
studies had a short follow-up and none considered the effect on adults with a
high baseline CD4 cell count; none looked at adherence to cotrimoxazole and
ART; no study reported the cause of death so the exact mechanism by which cotrimoxazole
improves survival is unclear. 

The authors conclude
“although the data…were limited and results from an on-going trial…awaited, our
findings support current WHO recommendations that the use of cotrimoxazole
should be scaled-up in HIV-infected individuals starting or getting ART.”

References