Achieving full coverage of
cotrimoxazole prophylaxis during the first six months of antiretroviral therapy
would be a highly cost-effective way of reducing early death among those with
advanced HIV infection in sub-Saharan Africa, researchers report in the advance
online edition of the Journal of Acquired
Immune Deficiency Syndromes.
The researchers developed a
decision-analytic model from a health care perspective to compare costs and
outcomes. Full cotrimoxazole prophylaxis coverage at an estimated additional cost
of $3.29 for each person on ART prevented an additional 22 deaths compared to
the base-case scenario (from 94 to 72 deaths per 1000 patients) at a cost of
$146.91 for each death prevented over the first six months.
Potential cost savings for specific
opportunistic infections (OIs) prevented by cotrimoxazole prophylaxis were also
Prevention of 45 new malaria
episodes per 1000 persons treated would save between $69.95 and $203.32 per
case averted, while prevention of 22 severe bacterial infections per 1000
persons would save between $68.62 and $126.71 per case averted. Prevention of
four new cases of pneumocystis pneumonia would save between $75.69 and $88.41per
An intervention is considered very cost-effective by the World Health Organization if the incremental cost per life-year saved is no greater than the GDP per capita; in the case of the poorest countries in Africa this was calculated at $1695 in 2005. This analysis is not strictly comparable because it calculates cost savings in deaths averted.
Over the past decade the increasing
availability and access to ART in resource-poor settings has resulted in
reductions in AIDS-related deaths.
Yet, in sub-Saharan Africa people
continue to present for care at an advanced stage of illness resulting in high
rates (8-20%) of early death after starting ART compared to North America and
Europe. Common causes of death include tuberculosis, pneumonia and diarrhoeal
In North America and Europe
it is common practice to give cotrimoxazole prophylaxis to those who present
for care with advanced HIV, primarily to prevent PCP. Its use in African
settings, however, appears to protect against a wider range of infections and
is not restricted to those with advanced HIV.
Recent studies in sub-Saharan
Africa, while not randomised, have shown a consistent reduction in death where
people on ART got cotrimoxazole compared to no cotrimoxazole, note the authors.
In particular cotrimoxazole has been shown to reduce the risk of tuberculosis
and of malaria in people taking antiretroviral therapy. A meta-analysis of seven studies shows that cotrimoxazole prophylaxis reduced the death rate in people taking antiretroviral therapy by almost 60%.
CTX, a relatively cheap
antibiotic, has been shown to be cost-effective and cost-saving among those not
on ART, and cost-effective when provided to all HIV-infected adults in a
treatment setting where ART was available for those with advanced illness.
The authors noted there have
been no cost-effectiveness analyses of cotrimoxazole provision and starting ART.
So they chose to look specifically at the effect of cotrimoxazole on reducing
death rates among those with advanced HIV illness in resource-poor settings
during the first six months on ART.
Six months was chosen because
studies have shown the risk of death to be the greatest during this time. Additionally
the DART trial showed the effect of cotrimoxazole on reducing death might
lessen over time with no further benefit after 72 weeks of ART.
Because cotrimoxazole is
already provided in a number of settings the authors chose to estimate the current
average rates of cotrimoxazole administration and compare it with close to full
coverage (65% and 97%, respectively) to look at the potential benefits of
increasing cotrimoxazole coverage in reducing deaths and OIs. Those allergic to
or intolerant of cotrimoxazole were excluded.
So the decision-analytic
model was developed to look at the additional cost, deaths and cases of OI
prevented and the incremental cost-effectiveness ratio (ICER).
The ICER was estimated as the
difference in health care utilisation costs at base-case and full coverage scenarios
divided by the difference in outcomes.
Health care costs (for people
getting ART) included routine outpatient visits and drugs (ARVs and cotrimoxazole).
Total cost was estimated as the total drug costs and six months outpatient care
assuming one routine visit.
The authors note the
difficulty in determining cost-effectiveness when using death as an outcome
measure. So their findings are not applicable to a willingness to pay (WTP)
context. That is, the maximum amount of monies a person is willing to pay to
achieve the desired result.
However, these findings are
comparable with studies looking at life-years saved/gained as the outcome
measure to show the effectiveness of cotrimoxazole for people with HIV. Studies
showing cotrimoxazole cost-effective among adults with HIV had ICERs ranging
from $150 to $1180 for each year of life gained compared to no cotrimoxazole.
Generic cost information for
ARVs and OI drugs were used since median costs for such goods are traded on the
international market so costs would be consistent across settings, note the
Outpatient and inpatient costs
were more difficult to generalise so the authors chose region-specific costs to
reflect a variety of low-income settings in sub-Saharan Africa; so limiting the
findings to comparable settings.
Other limitations include the
absence of randomisation among the studies that informed the assumption about
death rates and use of cotrimoxazole, the authors add. Ethically a randomised
trial is highly unlikely. However, they add the reductions in death were fairly
consistent but may not be generalizable to other settings where rates of OIs
The authors did not look specifically
at a common issue in many HIV treatment settings of drugs meant for people with
HIV being used for other conditions. This results in frequent stock-outs of cotrimoxazole
so increasing the costs and cost-effectiveness.
However, in further analysis
the authors doubled the base-case drug costs and the resulting favourable ICER
meant that a considerable supply of cotrimoxazole could be used for other
conditions but would still be cost-effective for ART patients.
They conclude “if [high cotrimoxazole
coverage] is achieved, expansion of access to cotrimoxazole during ART
initiation could have an important impact on the effectiveness of on-going HIV