International Seminar on Access to Treatment for HIV in Developing Countries  5-6 June 1998 London, UK

Dr Rachel Baggaley
Office of HIV/AIDS/STD
WHO, Geneva, Switzerland
 
Introduction: Needs of people with HIV
The needs of people with HIV are varied and need to be addressed. These include medical, psychological and social welfare needs.

Care for people with HIV
Care for people with HIV needs to be seen in the context of a continuum of care from the hospital through the local clinic and to the home. It should include the needs of the patient and his/her family and dependants where appropriate.

Chemotherapy for HIV
There are several types of chemotherapy for HIV. Preventive therapy for diseases such as TB, PCP, cotrimoxazole for pneumonia/sepsis have been effective in reducing morbidity. In addition, screening and treatment for infections, including sexually transmitted diseases, TB, or cervical screening is important as well as the treatment of OIs and HIV associated infections & tumours.

Antiretroviral (ARV) therapy is the first breakthrough in the treatment of HIV disease and in industrialized countries has been shown to prolong the lives of people with HIV.

ARVs may also be given as post exposure prophylaxis (PEP), where an individual, often after an occupational accident involving percutaneous exposure to infected blood is given a short course of ARVs immediately after exposure.

In the prevention of mother-to-child transmission, several different regimes are available, all of which administer zidovudine (ZDV or previously called AZT) to the mother in the last part of pregnancy, during labour and in some cases post labour. In most of the trials to date, women have been counselled not to breast feed.

ARV therapy is now widely used in industrialized countries to treat asymptomatic and symptomatic HIV disease, as the therapy lowers viral load and increases CD4 cell count. It has been shown that it can prevent and delay the onset of HIV symptoms, relieve current HIV symptoms, and return the individual to a better level of health, overall.

Advantages and disadvantages to ARV treatment
Advantages include a longer life, disappearance of symptoms, improved quality of life and delayed disease progression. As a result, there is decreased risk of hospitalization with the control of viral replication. On the other hand, ARV treatments can mean taking difficult regimen or suffering adverse reactions to the drugs. The development of drug resistance is being increasingly reported especially if people do not adhere strictly to their treatment regimens.

Administering ARV treatments has to be accompanied by counselling and it is important not to raise false hopes for terminally ill patients who may not respond, or in people who will not be able to continue to afford treatment. There are already many anecdotal examples of people in low income countries being supplied with a few weeks of ARVs and not being able to find funds to pay for any further treatment.

Cost is a major barrier to their widespread use in resource poor settings. The drugs alone are very expensive and the other medical services which are also required (trained doctors, expensive and complex blood tests, etc.) may not be easily available.

Current ARV options

• monotherapy: Monotherapy is no longer used to treat HIV disease since it is considered to be ineffective in the long run. Previous to the development of combination therapies, ZDV was previously used in monotherapy treatment. Monotherapy is currently only prescribed for use in lowering transmission rates from mother to child transmission and for post exposure prophylaxis.
• double therapy - 2 NRTIs (nucleoside reverse transcriptase inhibitors): Double therapy administers two drugs. Double therapy has inferior clinical and virological improvement, however, the dose regimes are easier to follow (thereby improving adherence) adverse effects are less common, and it is significantly cheaper than tri-therapy (including protease inhibitor) regimes.
•  tri- therapy/ 4 drug therapy / HAART: These forms of therapy either include at least one Protease Inhibitor (PI) or two NRTIs and one NNRTI (non-nucleoside reverse transcriptase inhibitor).

ARVs for HIV disease: economic considerations
Individual costs: Who will pay for the drugs? These medications are very expensive and need to be in constant supply - if treatment is interrupted resistance to ARVs may develop quickly. ARVs require careful monitoring, using expensive tests which require trained laboratory staff and sophisticated laboratory equipment.

Country costs: The costs to the country need to be calculated. Is the current healthcare infrastructure able to incorporate the needs of ARVs or will it require significant strengthening (or in some cases new creation) of the current system?

Affordability as % of drug budgets:  The World Bank ¹ has established the following variables to help determine the affordability of ARV therapy in relation to the current healthcare system.

• HIV seroprevalence
• known HIV seroprevalence
• economy
• fertility (this helps to determine mother to child transmission rates)
• health spending (public sector/private sector)
• drug prices
• current infrastructure
• current health care staff and training levels

Financing options

1. Public financing: in developed countries, the public sector normally covers 66% of drug costs. However in developing countries, this amount is usually below 20%.

2. Health insurance: In Latin America 35% of the population is covered by private health insurance. In Asia, the figure is 10% and in Africa, only 8% of the population is covered by health insurance. In addition, whether these insurance plans will cover HIV treatment and/ or prescription costs varies greatly from plan to plan and country to country.

3. Out-of-pocket payment:  50-90% of drugs are bought by households. Government services are beginning to depend more on user fees to fund health care.

4. Voluntary and other local financing: PLHA solidarity funds, especially north-south, are sometimes used by PLHA in the south to buy drugs. Drugs are also donated.

5. Donor financing: Donor focus for health is directed more at the health sector in general and less on particular diseases. For HIV, prevention is the main focus with less funding available for drugs.

6. Development loans: There has been an increase in World Bank health and pharmaceutical lending, but this is generally considered to be an interim measure.

ARVs for prevention of mother-to-child transmission: Summary of CDC Thailand Study

The regimen 

• 300 mg ZDV orally from 36 weeks gestation until the onset of labour.
• 300 mg every three hours from the onset of labour until delivery.
• All women were advised not to breast feed and were provided with infant formula.

Enrolment characteristics
The median age of women involved was 24 years and the median CD4 count was 424 cells/uL.

Adherence
The median duration of antenatal treatment was 24 days and the median number of labour doses was three. 99% of women took at least 90% of pills in the antepartum period and 99% took at least one dose during labour.

Results
Fifty-two of the 391 children were infected: 17 in the ZDV arm and 35 in the placebo arm.

The Kaplan-Meier estimates for transmission risk in the ZDV and placebo arms were 9.2% (95% confidence interval, 5.0%-13.5%) and 18.6% (95% confidence interval, 13.0%-24.0%), respectively, representing a 51% reduction in transmission risk (95% confidence interval, 15% - 71%).

The Thailand results demonstrate that a short course of twice-daily oral ZDV used from 36 weeks gestation until delivery was safe and reduced the risk for mother-infant HIV transmission by approximately one half. Following the release of the results, Glaxo Wellcome has announced a major reduction in the price of ZDV for use in prevention of mother-to-child transmission in developing countries, increasing the likelihood of this intervention being implemented.

There are several notes of caution, however, before basing further programmes on these results. This was only one trial with a high adherence rate. The medical infrastructure needed to deliver the medication and services was already in place with good staffing levels. In addition, bottle feeding is acceptable and not stigmatising in the Thai culture. No study has, as yet shown ARV s to lower mother to child transmission in a breast feeding population.

Mother to child transmission - general considerations
Guiding principles for setting up ARV services in maternal health services have minimum requirements and the costs for these requirements need to be evaluated.

ARVs for prevention of HIV transmission after occupational exposure
At what levels of risk the worker(s) need to be exposed to before accessing ARVs needs to be established ahead of time. Precise procedures and steps need to be established ahead of time, before a prophylaxis is needed. The costs of these procedures should be calculated.

Access to ARVs presents political, social, ethical, economic and medical challenges.
The national and local health systems must have capacity to diagnose and monitor these therapies and their proper use requires education of providers and patients. The treatment regimens are complex, and dangerous side effects and drug interactions are common. In addition, many of the priority drugs are extremely costly and not available from international low-cost suppliers. Improper use of ARVs lead to ineffective treatment and resistance.

Treatment effectiveness relies on continuum of care and social support network. The barriers to access are social, political, ethical, and not simply medical and economic. These barriers must be addressed before one can have an effective programme.

Discussion:
Dr Baggaley confirmed that WHO's minimum requirements for ARVs are guides to the minimum requirements for the health system before ARVs should be provided and not tied to funding.
 
 

References:

¹ Prescott, World Bank Confronting AIDS, A World Bank policy research report.  OUP, New York  1997.

² Comparing costs/DALYs from studies in industrialized and developing countries will reveal differences that have nothing to do with the "generic" cost effectiveness of an intervention, but will reflect differences in the relative price of labour etc. between the two countries.

³ Masergh G., Haddix A., Steketee R et al Cost effectiveness of short course zidovudine to prevent perinatal HIV 1 infection in a sub-Saharan African developing country setting. JAMA 1996 276:139-145

⁴ Marseille E., Kahn JC., Saba J., Cost effectiveness of antiviral drug therapy to reduce Mother to child transmission of HIV in sub-Saharan Africa AIDS 1998 12 939-948

⁵ See GLOBALRx Inc.

⁶ Allen S., Serufilira A., Bongaarts P., et al Confidential HIV testing and condom promotion in Africa  JAMA 1992 268 (23) 3338-44

⁷ Floyd & Gilks 1998 Guidance Modules on antiroviral treatments WHO/ASD 1998