PROGRAMME MONITORING

Robin Wood, BSc, B.\!, DT.HI:-H, .IHId, FCP (S.4)

Linda·Gai! Beller, .IIB ChB, FCP (SA), DT.HI:-H, PhD

HIV Research l.:nit, Departme711 of .\ledicine, c.;nit:ersity of Cape TO'C.:n

A proposed register documenting entry criteria and

recording ARV scheduled therapy would allow an overall
audit of programme performance in a similar fashion IQ
that of tne TB register. Incorporation of the national ID

number in conjunction with national death registration

data would allow calculation of the sUNival of patients

entering the programme on an 'intention to treat' basis

[Fig. 1).

There is a urgent need to establish a minimum data set

required to allow evaluation and comparison of ARV
projects in Africa.

programme will need to be of a similar magnitude to that

of the TB treatment programme and will face similar
challenges as high levels of adherence to potentially toxic

drugs are required for a prolonged period of time. The TB

control programme utilises a standard two-scheduled

approach to drug therapy, which simplifies the operational
implementation necessary for a large national programme.

ART TREATMENT REGISTER

The national TB register allows performance assessments to

be made of individual clinics and ultimately the programme

as a whole. Similarly, an ART scheduled approach would

simplify training and education of medical personnel and
would result in predictable patterns of toxicity and of

resistance. A predetermined standardised sequence of drug

combinations would also limit the number of drugs to be

procured and managed.

Comparison of these data with modelled survival of

patients determined by baseline characteristics at entry to

the programme would allow calculation of life-years

gained by the programme. A national ART programme

would utilise large quantities of relatively expensive drugs,

and the financial burden of poor drug accountability could

seriously undermine such a programme. The ARV treatment

AFFORDABLE NATIONAl HAART PROGRAMME

Examples of highly successful ARV programmes in

countries at a comparable stage of developmen to

sout ern African countries, and with similar socioeconomic

challenges, are the ARV (HAART) programmes incorporated

into tne Brazilian public health care system' and the pilot

projm instituted in rural Haiti, the poores country in the

Western hemisphere:

A concern that widespread, unregulated access to
antiretroviral (ARV) drugs in sub-Saharan Africa could lead

to the rapid emergence of resistant viral strains, spelling

doom for the individual, curtailing future treatment

options, and leading to transmission of resistan' virus, has

been voiced.' This pessimistic perception 0' the outcome of

HAART programmes in resource-poor settings is not
inevitable, if a well-organised national treatment plan is

developed.

Highly active antiretroviral therapy (HAART) has greatly
improved the prognosis of HIV-infected individuals in

a' uent countries, resulting in a marked drop in AIDS-

related mortality'·' In order to extend the benefits to
resource-poor countries, the World Health Organisation

[WHO) has called for expanded access to ART.'

Des ~lartin, .IfB ChB, .I'L\!,d, DT.I!&H, DPH

Uni',:miO' oJ tlu 1f'il"..::acmTand and HIV ClnlU;i.ans Societ)'

Penny Penhall

HW Clinicians S0ci2ty

PERCEPTIONS OF SOUTHERN AFRICAN AND OTHER
RESOURCE-POOR SffilNGS

NATIONAL ANTIRITROVIRAL TREATMENT
REGISTER - A NECESSITY?

Wi:n 360 000 estimated AIDS cases in South Afcca·' an ART

In ongoing discussions surrounding the roll-out of ARVs by

the state, cost is often mentioned as one of the 'problems:

In fact, a costing model of a rationed national HAART

programme has recently been shown to be affordable

within present South African budgetary constraints' and

elements of civil society are now demanding increased
access to HAART in the puolic health sector.;

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Fig, 1, Proposed web-based ART register.



Tilt SOUTlltRN MRICAN JOURNAL Of IIIV MEDICINE ------------

register at any institution could be reconciled against drug
purchases by that institution for drug accountability
purposes and to identify and avoid 'drug seepage: Specific

questions such as impact of prior exposure to mother-to-
child transmission preventive therapy on subsequent

response to ART could be answered by analysis of the
register database. Blood sampled at the time of failure of
the first schedule could also be stored for national viral

genotyping surveys, which could give information on
patterns of viral resistance, which in turn would allow

scientifically based changes in scheduled drug choices.

An ART register would need to be a standardised form that

could be in either paper- or web-based formats. As ART will

be provided at health care facilities other than TB clinics
the administration of the register would need to be the

responsibility of organisations such as the national or
provincial AIDS directorates.

OUTCOMES

The major outcomes of a successful ART programme would

be a decrease in AIDS morbidity and mortality. While CD4

cell counts, clinical stage and viral load determine

prognosis of untreated patients, effective viral suppression
by ART is the major determinant of outcome on treatment"

National and international ART guidelines have been

developed and published, which give clear initiation criteria

and recommended therapy combinations and could be

used as a basis for scheduled drug choice.'·"

LESSONS FROM THE TB CONTROL PROGRAMME

To encourage the correct usage of ART, it has been

suggested that the ART programme be closely linked to and

managed within the TB control programmes of sub-

Saharan Africa.' ART canno~ however, be isolated from the

wider comprehensive approach to HIV and AIDS patient

care, including management of the psychosocial and other

medical complications, such as prophylaxis and treatment

of opportunistic infection.'·' It would not be practical or
prudent to burden the TB control programme with this

heavy responsibility. A scheduled ART approach could be a

useful method to enable wider, more equitable access to

ART within our existing health infrastructure, and an ART

register would be a tool to monitor the overall performance

of such an expanded access programme. While expanded

access to ART should not be the responsibility of the TB

clinics, there may be important lessons to be learned from

the programmatic methodological approaches of the

national TB control programme.

PROTOCOL OUTUNE

The proposed register would be web-based with password-

protected access from registered PCs only. Entry of the
individual national identity number would lead to an

allocated site registration number, which would be used in
all future communications. The proposed format of the

register is shown in Fig. 1, and all data entry will be by
'point and click' menus. Baseline data will be entered

including age, sex, WHO stage and staging conditions,
baseline CD4 count and the initial treatment schedule

chosen by the practitioner. Subsequent changes in
treatment regimens would be categorised as due to

toxicity, drug intolerance or viral failure together with
dates of changes. The present drug regimen will be shown

in an automatically updated regimen box.

Blood samples for genotyping will be stored at each change

of therapy triggered by viral failure. Automatic e-mail

requests for patient status will be generated to confirm
whether subjects are still actively followed up or lost to

follow-up. Funding has been sought to perform genotype-

resistant pattern at the time of first failure of the second
regimen. It is intended that these data be made available to

the clinician for clinical decision-making.

REGISTER OUTPUTS

The register is intended to act as a pilot audit of current

ARV clinical practice and to develop a tool for monitoring

increasing widespread access to HAART. The primary aim is

to assess the overall prognosis of subjects initiating HAART
treatment in South Africa by establishing 'intention to

treat' survival. Secondary end points include length of time

on first non-nucleoside reverse transcriptase inhibitor

(NNRTI)-based regimen in clinical practice, time to first

virological failure and comparative tolerability of different
starting regimens. Initial viral resistance genotype data will

be made available for longitudinal population surveillance

of circulating pre-treatment resistant mutations.

Subsequent genotypic data will reflect viral response to

present drug pressure and aid clinicians' therapeutic

choices after failure of the protease inhibitor (PI)-based

regimen.

PARTICIPATION

It is envisaged that members of the SA HIV Clinicians

Society who are experienced treaters participate in the

programme by entering the password-protected Internet

site from registered Pes. As indicated above, the entry of
the individual national identity number would lead to an

allocated site registration number, which would be used in

all communications.

Participating medical practitioners would be required to

recruit drug-naive patients and be willing strictly to follow

the current HIV Clinicians Society guidelines. The initial

regimen would be an NNRTI-based regimen and the

MAY 2003



GUIDELINES

Gayle G Sherman, ME BCh, DCH (SA), DTM&H, MMed (Haem)

Department of Molecular Medicine and HamullOfggy.Johannesburg Hospiuzl. Nazional Health Labararory Service and University of cbe

Wi",,,,umand, ]oiuznmJlnng

INFANT HN DIAGNOSTIC GUIDELINES TO
FACILITATE ADOPTION

!>errings: Guidelines for a Public Health Approach. Geneva: WHO, 2002-
5. Harries AD, Nyangu1u os. Hargreaves NJ, Kaluwa 0, Salaniponi FM. Pr~enting

antiretroviral anarchy in sub-Saharan Africa Lancet 2001; 358: 410-414.
6. lrli GC, Vitoria MA. Fighting against AIDS: Tn/:' Brazilian ~jence. AIDS 2002; 16:

2373~238J.

7. Farmtt P, ~nd(e F, Mukherjee 15, ~r aL Community-based approach~ to HIV
uea!metlt in (~urct·poor settings.. Lona:r200l; 358: 404-409.

a Soulle A. Kenyan C. Skordis J, Wood R. Rationing HAART Part I: An ~Iotation of
the rosts of a limited public sector antiretroviral ueatmem programm~ in South
Africa. SAf, MN)2002; 92: 811-817.

9. BredeU COnsetlSUS Statement on the Irrperative to Expand Acttss to AntireuoviraJ
Medicin~ fur Adults and O1ildren with HfV{A1DS in South Africa. NovefflOO- 2001.
National Tret1tmenr Congress Resourct Docum~nr Numb~r 12. Cape Town:
Treatment Action Campaign.

10. Report on the global HIVIAlDS epidemic. Joint United Nations Programme on
HN!AlDS (UNA/oSj. Geneva: UNAIDS, July 2002.

11. Egger M, May M, Chene G, et al. Prognosis of HIV-1-infe<:ted patients starting
highly active antiretroviral tIlerapy: a collaborative analysis of prospective studies.
Lancer 2002; 360: 119-129.

12. Southern African HIV Clinicians Society. Clinical Guidelines: Antiretroviral Therapy
in Adults. June 2002 vtrsion. Sourhern African Journal of HN Medicine 2002; July
(Issue 8): 22~29.

The qualitative HIV polymerase chain reaction (PCR) test is

highly specific for HIV infection, but sensitivity varies with

the age of the infant' The PeR identifies approximately

50% of infected infants at or just after birth and> 95% at

3 - 6 months of age" More recent evidence suggests that

HIV PCR tests performed at ~ 1 month of age have a
sensitivity of ~ 95% and specificity of > 99<\'0.' The Roche

Amplicor Kit (Roche Molecular Systems, Somerville, NJ)

------------- THE SOUTHERN AFRICAN JOURNAL OF HIV MEDICINE

1. Morcroft Po, \/tlla 5, Benfield n.. eta/' Changing mortality across Europe in patients
infected with HN-1. Lancet 1998; 352: 1725- 1730.
Moore Ro, Chaisson RE. Natural history of HIV infection in the era of combination
antiretroviral therapy. AIDS 1999; 13: 1933-1942

3. Palella FJ, DeJaney KM, Moorman AC, er 01. Declining morbidity and mortality among
patients with advanced human immunodeficiency virus in~tion. N EnglJ MM
1998; 338: 853-860.

4 World Health Organisation. Scaling Up Anrirecrovirol Therapy in R~Itt-Lim;red

subsequent or second-line regimen would be PI-based.

REFERENCES

Any interested treaters who would like to participate
should e-mail the managing editor of the Southern African
Journal of HIV Medicine at Igbekker@cormack.uctac.za,

expressing the number of patients likely to be treated at
their site in the next year.

South Africa is currently estimated to have 300 000

HIV/AIDS orphans, and the figure is likely to increase to

2 million by 2015.' Facilitating adoption of children

affected by HIV provides a highly effective strategy for

addressing the HIV/AIDS orphan crisis, albeit on a very

small scale. The legal and ethical issues surrounding HIV

testing of abandoned children for the purposes of adoption
are not addressed here.

These guidelines were contributed to and are endorsed by:
Or Ashraf H Coovadia
Department of FlJediorrics, Coronation Hospital, and University of the Witwatersrand
Or Mark F Cotton
FlJediatric Infectious Disease Unit Tygerberg Children's Hospito( University ofSte/lenbosch
Or Glenda E Gray
Perinatal HIV Research Unit Chris Hani-Barogwanath Hospital and University of the Witwatersrand
Professor Gregory 0 Hussey
School of Child and Adolescent Health, University of Cape Town
Or Leon J levi n
Puediatn·cian in pfNate practice
Or Tammy M Merers
Department of FlJediatrics, Chris Hani-Baragwanath Hospital and University of the Witwatersrand
Professor Lynn Morris
AiDS Unit National Institute for Communicable Diseases and University of the Witwatersrand
Or Adrian J Puren
National Institute for Communicable Diseases and University of the Witwatersrand
Or Wendy 5 Stevens
Department of Molecular Medicine and Haematology. National Health Laborotory Service and University of the Witwatersrond
Or Lynne M Webber
Department ofMedical Virology, University of Pretoria

MAY 2003