1

Evaluation of Antiretroviral Therapy Followed by an Educational Intervention to Increase Appropriate Use in Zimbabwe

Tisocki Klara, Sibindi Siboniso, Maguma Hercules, University of Zimbabwe

Problem Statement: The inappropriate use of antiretrovirals (ARVs) can quickly lead to development of viral resistance, treatment failure, toxicities, and waste of financial resources. Objective: To evaluate physicians’ prescribing practices for ART for adult HIV/AIDS patients in Zimbabwe; and to design and pilot-test an educational intervention to increase the rational use of ARVs.

Design: Descriptive study based on retrospective data collection; and before/after study based on self-administered questionnaires.Setting and Population: Private physicians in Zimbabwe. Individual patient data were collected on the following: patients’ assessment prior to starting ART; prescribing patterns; monitoring for efficacy/safety; and clinical/virological outcomes. Intervention: The educational intervention comprised face-to-face training in appropriate use of ART supported by printed materials designed and tested in individual academic detailing visits to 13 physicians.Outcome Measures: Individual patient data analysis in the above four domains (assessment prior to ART; prescribing patterns; monitoring for efficacy/safety of therapy; and clinical, virological outcomes); changes in physicians’ knowledge about rational use of ARTs.

Results: 41% of patients had no record of any initial clinical evaluation and only 6% of patients had all of the recommended laboratory tests performed. Approximately half of the patients (56%) were initiated on triple therapy, and 34% on dual therapy. Thirty-eight percent of patients received regimens with incorrect doses. Sequencing of ART frequently occurred from triple to dual therapy, based mainly on the patient's financial status rather than on the efficacy or safety profile of regimens. Opportunistic infections and HIV-related malignancies were used primarily to monitor efficacy. Unfavorable clinical/immunological outcomes were frequently present in patients receiving dual or monotherapy. Evaluation of the effect of the educational intervention showed an average 27.15% increase in knowledge, as evident from comparison of pre- and post-intervention questionnaires. The highest increases were found in knowledge on drug interactions and adverse effects of ART.

Conclusions: Irrational prescribing of ART by private practitioners, leading to poor outcomes, were detected in the descriptive phase of this study. Independent academic detailing supported by practical printed information can be useful for improving use of ART and for the dissemination of evidence-based clinical guidelines.

2

BACKGROUND & SETTINGS

• Zimbabwe has one of the world’s highest HIV infection rate.

• In the late 1990s physicians in Zimbabwe started to prescribe ARVT to private sector patients with widely varying standards.

• ANTIRETROVIRAL THERAPY (ARVT) can dramatically reduce HIV/AIDS related morbidity and mortality– BUT it has narrow therapeutic margin i.e.

unless it is initiated, monitored, maintained and adjusted correctly, benefits may barely outweigh potential risks.

• POTENTIAL PROBLEMS OF ARVT in case of irrational prescribing include:– subtherapeutic effects and emergence of

viral resistance treatment failure, • Length of desired outcomes in individual

patient is reduced • Efficacy of ARVs within the population is

reduced

– unnecessary toxicity, – wastage of limited financial resources

• Affecting heavily surviving family members

3

OBJECTIVES

I. To examine standards of providing ARVT in Zimbabwean patients receiving treatment in the private health sector by investigating:

• initiation,

• monitoring and

• evaluation of ARVT and

• relevant patient outcomes

II. To design and pilot-test an educational intervention promoting the rational use of ARVs by increasing the physician’s knowledge about evidence-based and rational use of ARVs

4

METHODS 1.

Objective I. Examine patterns of ARVT

Design: Descriptive study based on retrospective data collection

Subjects: 14 physicians prescribing ARVT in main urban centers (Bulawayo, Harare) identified by a screening questionnaire

Data collection: January – February 2001• individual patient data was retrospectively

extracted from medical records of 39 patients.– Inclusion criteria: above 18 years, received at

least one ARV for at least a six months; data available for the last 12 months.

– Exclusion criteria: ARVT given for prevention of mother to child transmission or for post exposure prophylaxis .

Data Collected: – Clinical, laboratory and virological evaluation

before and during ARVT

– Initial ARV regimen and consequent changes

– Monitoring for efficacy and safety

– Clinical and immunological outcomesSee yellow data collection sheets in right corner.

Data analysis: descriptive statistics

5

METHODS 2.Objective II. Promote rational use of

ARVs by increasing physicians’ knowledge

Design: Pilot-test an educational intervention with pre- and post intervention assessment of effectiveness

Intervention: Academic detailing combined with distribution of concise printed materials– Single, structured face-to-face meeting

conducted by specially trained pharmacist in physician’s surgery

– Concise information booklet summarising evidence-based clinical guideline recommendations complemented with laminated desktop info-cards See material in left corner of poster

Subjects: 13 Physicians prescribing ARVT inthe private health sector (Harare)

Assessment: Multiple choice questions randomly divided into pre and post tests that were administered two weeks before and two weeks after the intervention

Data analysis: comparison of pre and post intervention scores

6

CLINICAL EVALUATION BEFORE STARTING ARV

Clinical evaluation No. of patients n=39

1, 2, 3 and 4 7 (18%)

1, 3 and 4 4 (10%)

4 only 3 (8%)

1 and 3 3 (8%)

3 and 4 6 (15%)

No evidence of 16 (41%) any clinical evaluation

Key:

1 = weight

2 = chest x-ray

3 = examination of the oropharyngeal mucosa

4 =examination of skin and lymph nodes

Important observations:

• Only 18% patients received full clinical evaluation as recommended

• 41% had no records of any clinical examination

• Complete laboratory examinations incl. CD4, TLC, VL, LFT, FBC was performed in only 2 patients (6%)

7

INITIAL AND CURRENT ARVT REGIMEN

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

2NRTI + 1PI 2NRTI +1NNRTI

1NRTI + 1PI 2NRTI' DDI + HYU

% o

f pat

ient

s

Initial regimen

Current regimen

Important observations: • Patients were frequently switched to dual

therapy with NRTI+PI or 2NRTI combinations or to quasi monotherapy with DDI+hydroxyurea

8

PRESCRIBING OF ARVs

Incorrect dose of ARVs was found in total of 15 patients (38%), examples:– AZT (67% of effective dose prescribed ),

occurred in 7 pts.– underdosing of SQV (22% of effective

dose prescribed) occurred in 2pt. – Double dose of DDI

• Interactions:– co-administration of Indinavir and

Rifampicin

• Irrational combinations i.e. – AZT + hydroxyurea, 3TC+ hydroxyurea

• irrational first-line therapy i.e. – Didanosine + hydroxyurea combination

• irrational sequencing i.e. – Patients were frequently switched from

triple to dual then monotherapy– DDI+ HYU was the current therapy for 7

pts. (18%)

9

CLINICAL AND IMMUNOLOGICAL OUTCOMES

OUTCOME No. of Pt. DRUG REGIMEN

1, 7 and 3 8 (21%) 2NRTI's + 1PI or 2NRTI's+1NNRTI

1 and 4 8 (21%) 2NRTI's + 1PI1NNRTI+1PI;1 NRTI + 2NNRTI

1 only 2 (6%) 2NRTI's + 1PI2 and 4 1 (3%) DDI and HYU6 and 3 2 (5%) 2NRTI's and 1PI4 only 6 (15%) 2NRTI's4 and 5 12 (15%) DDI and HYU,

2NRTI's

Key: 1 = Undectateble viral load; 2 = High viral load, 3 = CD4 count>350cells/mm3 4 = CD4 count <350cells/mm3

5 = Clinically unwell with OIs 6 = Low viral load <10000cop/ml, 7 = clinically well

Important observations: • Desired outcomes (undetectable VL, high

CD4, clinically well) was found generally in pts on triple ARV regimens

• Dual or monotherapy often resulted in poor outcomes in spite of ARVT

10

EDUCATIONAL INTERVENTION

• Structured academic detailing was developed delivering key messages regarding:– Goals of and starting ARVT – Choices for ARVT and potential drug

interactions– Monitoring adherence and side effects – When to change therapy– Use of hydroxyurea in ARVT– Use of antiretrovirals for PMTCT

• Single face-to-face academic detailing session lasted approx. 30 to 90 min. were delivered to 15 physicians. Some physician requested a second visit from the pharmacist.

• This was combined with printed educational material to facilitate access to information and re-inforce key messages

• Assessment of the effect of the educational intervention (based on 10 phsysicians completeing the full study) showed an average 27.15% increase in knowledge og physicians.

• The highest increases were found in knowledge on drug interactions and adverse effects of ART.

11

DISCUSSION• Though small in numbers, Zimbabwean patients

living with HIV/AIDS trying to access ARVT in the private health sector.

• In spite of continued use of antiretrovirals in majority of patients immunological and clinical outcomes were poor, possibly due to irrational choices and poor monitoring

• ARVT has rapidly evolved in the last decade and physicians were often poorly informed about the latest evidence-based clinical guidelines and on how to optimize ARVT.

• In addition, the high cost of the therapy often forces patient-physician decisions towards irrational choices or sequencing in ARVT.

• Academic detailing delivered by pharmacist and combined with evidence-based information on ARVT from reliable, independent sources was well received and appreciated by physicians.

• Locally generated information can be well-focused and specific for ARVs available on the market in Zimbabwe.

12

SUMMARY• Wide variations were found in prescribing,

monitoring and evaluation of ARVT in the private health sector in Zimbabwe.

• Consequently, patient outcomes were also varied considerably, with poor results for the majority.

• Academic detailing by the pharmacist combined with provision of printed information increased physician’s knowledge on ARVT.

RECOMMENDATIONS• Comprehensive training of prescribers is

urgently needed in order to achieve maximum possible benefits while minimising risks from ARVT.

• Pharmacists providing locally developed and focused information can be valuable resource in prescriber’s education.

• Reduction in prices of ARVs and necessary tests is stills needed. Even though international public procurement prices fell dramatically this often does not translate into real affordability for patients in the private health sector. High prices can continue to force irrational choices or poor adherence defeating the main goals of ARVT.