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OPINION
HOW SHOULD WE CARE FOR PATIENTS WHO ARE NOT YET ELIGIBLE FOR ART?
Tom H Boyles1,2,
MA, BM BCh, MRCP, DTM&H, MD
Lynne S Wilkinson1,3,
BA, LLB
1Madwaleni Hospital, E Cape
2Division of Infectious Diseases and HIV Medicine, Department of Medicine, Groote Schuur Hospital and University of Cape Town
3Médecins Sans Frontières, Cape Town
In 2009, there were an estimated 5.6 million people living with HIV in South Africa.1
Based on a threshold of CD4 <350 cells/µl, it is estimated
that around 46% of patients are not yet eligible for antiretroviral
therapy (ART).2 The Department of Health guidelines from 20103
have limited recommendations for the care of patients not eligible for
ART. There is no guidance on how to develop a package of care or how
roles should be assigned between different cadres of staff. It is
unclear whether pre-ART care services are currently being offered to
large numbers of patients, and it is our opinion that comprehensive
guidelines based on effective models of pre-ART care are urgently
needed. We believe that this has the potential to reduce morbidity,
mortality and transmission and increase long-term retention in care in
South Africa.
Currently, rates of retention in pre-ART care are disappointing. A
recent review of studies from sub-Saharan Africa found that the median
proportion of patients lost to care was 59% between testing and receipt
of CD4 counts, 46% between staging and ART eligibility, and 68% between
ART eligibility and initiation.4
Based on the information available, only about 18% of patients who are
not yet eligible for ART when diagnosed with HIV remain continuously in
care until ART eligibility. Although some patients may enter care
elsewhere, others may only present again when unwell and some time
after becoming eligible for ART. The median starting CD4 count of
patients in South Africa remains well below the level at which patients
become eligible for ART,5
and loss to care of ineligible patients is likely to be an important
contributor to this. Low CD4 nadir is associated with poor clinical
outcomes7 and increased costs.8
In response, calls have been made for significantly improved adherence
to pre-ART care and monitoring of patients not yet eligible for ART to
achieve AIDS strategy goals and reduce the problem of late presentation
and initiation of ART.9
One reason for low retention in care in the pre-ART period may be
lack of availability of comprehensive HIV care services. Patients
simply asked to return for repeat CD4 testing after 6 months may be
less inclined to return than patients offered a comprehensive service
package upon diagnosis. Another reason may be a perception among
patients that ART is only necessary as a last resort when becoming sick
despite other attempts to remain well while living with HIV. The 2003
World Health Organization (WHO) recommendations for ART in
resource-limited settings were to start ART when the CD4 count dropped
to ≤200 cells/µl or the patient developed WHO stage 4 illness.10
This message was interpreted by many as ART only being necessary when
one becomes sick. Many people’s only experience of ART was seeing
it prescribed to sick and late-presenting patients, which served to
reinforce the misunderstanding. The 2010 WHO recommendations (adopted
by South Africa in August 2011) that all patients with a CD4 ≤350
cells/µl initiate ART11
were widely welcomed by campaigners. However, there was a word of
caution from Vuyiseka Dubula, the General Secretary of the Treatment
Action Campaign in South Africa, who explained: ‘... our
communities were made to believe we only needed ART when we were sick,
now we have a massive task ahead of us to change deeply entrenched
community perceptions’ (personal communication). It may take some
time for communities to buy into the importance of accessing ART early,
and engagement of patients not yet eligible for ART is an ideal forum
to begin.
Our own service model in the rural Eastern Cape province of South
Africa provides an example of how effective comprehensive HIV services
including pre-ART care can be delivered.12 Outcomes analysis of
1 803 patients initiating ART found that the 270 who had received >6
months pre-ART care started ART at higher CD4 counts than the cohort as
a whole (192 v. 123). Notably, receiving >6 months pre-ART care was
independently associated with clinically relevant outcomes including a
50% reduction in both mortality and loss to follow-up (LTFU) after
starting ART. This was an observational study with some selection bias,
as the pre-ART care group were included as a result of being adherent
to the pre-ART care programme for at least 6 months. This is more
likely to explain the differences in LTFU than those in starting CD4
count and mortality. Data from the private sector in South Africa also
show that patients receiving pre-ART care incur lower overall direct
costs.13
Our service model focuses on engaging patients in peer educator-led
community care groups immediately upon testing positive, regardless of
eligibility for ART. Groups are run on a weekly basis and are
decentralised to local primary healthcare clinics with patients usually
choosing to attend the group nearest their home. Meetings begin with
group education around a specific topic facilitated by a peer educator;
examples include the importance of ART adherence and the long-term
side-effects of ART. Each patient has a paper file held at the clinic,
and at each attendance the peer educators record weight and replies to
specific screening questions about tuberculosis and sexually
transmitted infection (STI), and ask whether there are any other
symptoms. Patients with weight loss or any symptoms are referred to the
clinic nurse on the same day. Pre-ART patients are prescribed
multivitamins or co-trimoxazole and counts of returned pills are used
to assess readiness for ART. Peer educators also provide one-on-one
counselling for patients preparing for ART.
Groups are fully integrated between those on ART and those who are
not yet eligible. This approach has allowed groups to grow quickly and
may have reduced HIV-related stigma in the community. Depression is
common following a diagnosis of HIV and may be worse in areas with high
levels of stigma.14 Depression is associated with both reduced linkage to care and impaired adherence to ART,16 but can be effectively treated with interpersonal support group therapy.17
The formation of community support groups of patients who have
disclosed their HIV status to the group may prevent depression and
improve retention in care in newly diagnosed patients. Incentives to
remain in long-term pre-ART care include the provision of prophylactic
medication such as isoniazid preventive therapy (IPT), access to
screening services such as Pap smears, and inclusion in the social
activities associated with joining a community group.
Until universal ART coverage is achieved in South Africa it is
likely that resources will predominantly be concentrated on ART
delivery, and it is important that pre-ART services are delivered in
the most resource-efficient way. In our service model the majority of
tasks are performed by lay counsellors. Referrals to nurses are only
made for specific clinical reasons (Fig. 1). While our care groups are
run on clinic premises, it would be preferable to move them out of the
clinic altogether and into the community. Innovative approaches to
community-led pre-ART care could be adapted from successful community
ART models, which have been shown to reduce the burden on healthcare
facilities and achieve higher rates of retention in care.18
The WHO recommends at least 6 months of IPT for all HIV-positive
adolescents and adults with latent tuberculosis, whether or not on ART.19 By the end of 2009, only around 85 000 people with HIV had received IPT, representing <0.3% coverage worldwide.20
ART-ineligible patients are a large group who could be targeted to
increase IPT coverage. IPT is an ideal component of pre-ART care as it
provides a tangible treatment option and allows monitoring of adherence
issues. Distribution of free co-trimoxazole has been shown to decrease
loss to follow-up in patients not yet eligible for ART,21
and it is likely that IPT would have a similar effect. Prescribing IPT
in the pre-ART period reduces the risk of overlapping drug toxicities
and high pill burden once ART is commenced. Additional benefits are
that active tuberculosis must be ruled out before prescribing IPT,
which increases active case finding.
Proven HIV prevention interventions to be included in pre-ART care
include treatment for sexually transmitted infections after symptom
screening by lay counsellors,22 condom promotion and distribution,23 contraception24 and pregnancy planning services.25
Initiating ART at CD4 counts >350 cells/µl for patients in
serodiscordant couples is a highly effective prevention strategy26 that could be implemented more easily if patients were retained in active pre-ART care.
Improved patient preparation has been shown to improve retention in care rates on ART.27
Patients who are ineligible for ART at the time of diagnosis may
benefit from extended ART preparation, giving them extra time to adjust
to the need for lifelong therapy and to attend multiple group education
sessions. Early preparation and retention of ineligible patients also
allows programmes to respond quickly to changes in eligibility criteria.
There are many challenges to providing comprehensive HIV services
and more data are required to inform us of the cost and benefits. It is
unlikely that a single model will be appropriate for all settings, and
consultation with patients should guide local programme models. Our
experience suggests that important features in any setting will be
delivering services close to people’s homes or jobs, integrating
services with those of patients already on ART, and task shifting to
appropriate cadres of staff. Our opinion is that no time should be
wasted in integrating active management of patients not yet eligible
for ART into programme models. We believe this can have a major public
health impact by reducing morbidity, mortality and transmission and by
increasing long-term retention in care. Furthermore, this can be
achieved without overburdening an already stretched healthcare service.
The authors declare no conflicts of interest.
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Fig. 1. Service package delivered in pre-ART services by various cadres of staff.