of death and illness remained 'substantial' even at higher CD4 cell counts
among people receiving antiretroviral therapy in lower-income settings, and much
greater efforts to get people onto treatment earlier will be needed to reduce
this burden in people living with HIV, according to findings of an
international review of treatment outcomes in seven countries published in the Journal of Acquired Immune Deficiency
analysis pooled data from 13 cohorts in five sub-Saharan and two Asian
countries, comprising close to 4000 adults who received ART between 1998 and
found that, although patterns of mortality according to current CD4 cell count
were similar to those seen in Europe and North America,
people living with HIV in lower-income settings remain at higher risk of
developing AIDS-defining illnesses at all CD4 counts when compared to their
counterparts in European cohort studies.
half of all the AIDS-defining events in these cohorts were cases of pulmonary
or disseminated tuberculosis (TB), which may occur at CD4 cell counts above 200. TB
is less likely to develop in people with higher CD4 cell counts, and for this
reason there has been strong advocacy for earlier antiretroviral treatment in
order to limit cases of TB in settings where TB transmission is endemic and
where a high proportion of people are likely to be latently infected with TB.
in 2009, the objective of the ANRS 12222 collaboration is to describe
CD4-specific rates of death and disease among people with HIV in resource-poor
authors pooled available data from cohorts of HIV-infected adults on ART in
five sub-Saharan African (Benin,
Burkina Faso, Cameroon, Ivory Coast and Senegal)
and two Asian (Cambodia and Laos)
countries to estimate CD4-specific rates of death and AIDS-related disease.
cell count is the most important predictor of HIV-related death and disease.
Incidence rates of death and disease by CD4 cell count for people on ART in
resource-poor settings have mostly been estimated in the low CD4 cell count range
based on pre-ART CD4 values.
on rates of death or illness according to on-treatment CD4 counts is limited,
and more complete information could demonstrate the extent of the burden of
illness and death that is not being prevented as a result of current recommendations
this analysis, cohort eligibility was based on initial study procedures
including: repeated CD4 cell count measurements; a follow-up period on ART; and
an active strategy to retain patients. Within the eligible cohorts inclusion of
patients comprised: being 18 years of age or above at enrolment; having at
least one CD4 count measurement available; and followed-up at least one day on
cell count strata considered were: under 50, 51-100, 101-200, 201-350, 351-500,
501-650 and over 650 cells/mm3.
incidence rates of death, of AIDS, or a combined criterion of death or AIDS and
of loss to follow-up per 100 person-years were estimated by dividing the number
of first events [since starting ART] happening within a specific CD4 stratum
divided by the time spent within the stratum.
the 3917 adults (2318 in Africa and 1599 in Asia)
with a cumulated follow-up of 10,154 person-years, two-thirds were female, the
median age was 34 years and median CD4 cell count before ART was 148 cells/mm3.
third was in the 201 to 350 cells/mm3 stratum and close to a half in
the over 350 cells/mm3 stratum. Median follow-up was 2.3 years and
the median number of CD4 counts for each person was six.
rates in the under 50, 51-100, 101-200, 201-350, 351-500, 501-650 and above 650
cells/mm3stratum were 20.6, 11.8, 6.7, 3.3, 1.8, 0.9 and 0.3 per 100
person-years, respectively. The corresponding AIDS-defining disease rate by CD4
count was 50.5, 32.9, 11.5, 4.8, 2.8, 2.2 and 2.2 per 100 person-years,
most frequent AIDS-defining events included: pulmonary tuberculosis,
disseminated tuberculosis, recurrent bacterial pneumonia, cryptococcosis, CMV
infection, toxoplasmosis, oesophageal candidiasis, Kaposi’s sarcoma, wasting
syndrome, non-tuberculosis mycobacteriosis and systemic mycosis.
to follow-up decreased with increasing CD4 counts (4.9, 6.1, 3.5, 3.1, 2.9, 1.7
and 1.2 per 100 person-years, respectively) with no significant difference
between the first and following years.
rates among males have been reported as consistently higher than among females.
Three-quarters of patients included in the studies from resource-rich settings
were male, while in their analysis two-thirds were female, note the authors.
main limitation was the relatively small sample size especially among those
with counts under 100 cells/mm3. This also prevented analysis of the
major determinants of death and disease for example, gender, age and time on
ART beyond the first year. The authors suggest data in larger and longer-term
cohorts would be useful.
authors propose three recommendations drawn, directly and indirectly, from
economic crisis and its impact on HIV/AIDS funding national AIDS programmes
must not be swayed from implementing the World Health Organization (WHO) 2010 recommendations
of raising the threshold of starting ART in asymptomatic patients from 200
cells/mm3 to 350 cells/mm3. In the near future – as in
resource-rich settings – starting ART above 350 cells/mm3 should be
means necessary to improve diagnosis and treatment of opportunistic infections
in patients on ART include laboratory equipment, training, mentoring and
supervision of healthcare workers, accessibility to preventive and curative
drugs and education of patients.
- Scheduling of
clinical visits must take into account not only the time on ART but also the
current CD4 cell count, a finding that further supports the need for
immunological monitoring in patients on treatment.
conclude: “Death and AIDS rates remained substantial after starting ART even in
people with high CD4 cell counts. Ensuring earlier ART initiation and
optimising case finding and treatment for AIDS-defining diseases should be seen