Dual therapy inadequate for resource poor countries

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at the Sixth International Congress on AIDS in Asia and the Pacific (6-10th October), Melbourne, Australia.

The urgent need for triple combination antiretroviral therapy for HIV infection in developing countries was highlighted in a session on opportunistic infections (OIs) at the Sixth International Congress on AIDS in the Asia and the Pacific (6th - 10th October), Melbourne, Australia.

Several studies presented today showed that people in Asian countries are often diagnosed when they have advanced HIV. For example, at the Preah Bat Norodom Sihanouk Hospital in Phnom Penh, Cambodia, more than 70% of HIV-infected patients in one study were diagnosed clinically upon presentation to hospital with symptoms of advanced HIV. More than three-quarters had a CD4 count of less than 50 and over 40% had a CD4 count below 10 (Chhin). Consequently, the prevalence of OIs was extremely high, with more than half of patients presenting with two or more concurrent opportunistic illnesses. The death rate among in-patients was 40%.

Glossary

cryptococcosis

A type of fungal infection usually affecting the membrane around the brain, causing meningitis. It can also affect the lungs and chest.

advanced HIV

A modern term that is often preferred to 'AIDS'. The World Health Organization criteria for advanced HIV disease is a CD4 cell count below 200 or symptoms of stage 3 or 4 in adults and adolescents. All HIV-positive children younger than five years of age are considered to have advanced HIV disease.

meningitis

Inflammation of the outer lining of the brain. Potential causes include bacterial or viral infections.

 

combination therapy

A therapy composed of several drugs available either as separate tablets, or as fixed-dose combination (FDC).

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

Dr Greg Rozycki conducted a retrospective, cross-sectional chart review of all patients attending the Preah Bat Norodom Sihanouk Hospital, between January 2000 and April 2001. He reported that cryptococcal meningitis was one of the most common opportunistic infections among this patient population. Of the 89 patients who met the study’s strict inclusion criteria (including documented HIV infection and a lumbar puncture performed on site), 49% died in hospital of cryptococcal meningitis. No factors were statistically associated with risk of death, although there was a trend to lower CD4 count among those who died (12.9 versus 43.5).

Dr Rozycki told the session that the high death rate indicates the need for increased use of antiretrovirals, earlier diagnosis of HIV infection and improved health care.

Dr Pimjai Satasit reported on opportunistic infections and use of antiretroviral therapy among HIV-infected patients in three public hospitals in Thailand. The most common OIs were tuberculosis, oral candidiasis, prurititic popular eruption, cryptococcosis and herpes zoster. This study showed the incidence of OIs among patients on antiretroviral monotherapy was 60% compared with a 10% incidence among people taking dual therapy. OI prophylaxis failed to reduce the rate of OIs among highly immune-suppressed patients.

Dr Rozycki told the session that these findings indicate the need for aggressive treatment prior to advanced disease and that “reconstitution of the immune system is the most cost effective way of preventing infection”.

Calls for access to antiretrovirals

The issue of access to antiretroviral treatment for people in developing countries has been a major theme of the congress. International AIDS Society President, Dr Stefano Vella, has called for developed countries to provide between US$7 to 9 billion to ensure triple combination antiretroviral therapy for HIV-infected people in developing countries.

“The ‘North’ of the world should take this financial burden,” Dr Vella said, “for drugs, and also for the infrastructure and capacity to deliver them.” He said that provision of antiretroviral therapy would ensure global security as well as humanitarian relief.

Dr Vella highlighted the recent falls in the cost of antiretrovirals to insist that provision of the drugs is possible. He said that a triple combination could be made available for US$300 per year per patient.

Accompanying such calls for provision of treatments globally, activists from the Coalition of Regional Networks, or the ‘Seven Sisters’, staged a treatments access demonstration on Sunday 7th October calling for access to affordable antiretrovirals for all HIV-infected people.

Two or three drugs?

Conference delegates from some countries, such as India, raised the question of the minimum standard of care within a context of high numbers of infected people and scarce resources during a ‘Meet the Experts’ session on Saturday 6th October. Discussion focused on whether patients in resource-poor settings could be treated with two antiretrovirals.

Professor David Cooper, of the National Centre in HIV Epidemiology and Clinical Research in Sydney argued strongly against such as strategy. He said that physicians in developed countries had been devastated by the short-lived benefits of dual therapy in among their patients during the early to mid-1990s. Dual therapy usually leads to drug resistance and treatment failure.

His commitment to triple therapy was supported by Celina D’Costa, Vice-President of the Indian Network of People Living with HIV/AIDS. Ms D’Costa refused to advocate for the short-term benefits of dual therapy and instead argued that all people living with HIV/AIDS should have access to the triple combination therapy and the sustained health benefits it provides.

One strategy Professor Cooper suggested for resource-poor settings was the commencement of triple combination therapy when the CD4 count fell to around 200. This is outside most current treatment guidelines (apart from those of the United Kingdom), but Professor Cooper said that existing data suggest that there is no survival advantage to commencing treatment earlier, although people who delay treatment until their CD4 count is 200 are at risk of opportunistic infections, some of which may be life-threatening.

References

Chhin S et al. Spectrum of opportunistic infections in hospitalized HIV-infected patients in Phnom Penh, Cambodia. Sixth International Congress on AIDS in Asia and the Pacific, Melbourne, poster Tuesday 1112, 2001.

Rozycki G, Chhin S et al. Etiology of meningitis among HIV infected inpatients in Phnom Penh, Cambodia. Sixth International Congress on AIDS in Asia and the Pacific, Melbourne, abstract 1352, 2001.

Satasit P et al. Opportunistic infections among HIV-infected persons and AIDS patients receiving antiretroviral in three hospitals of Ministry of Public Health. Sixth International Congress on AIDS in Asia and the Pacific, Melbourne, abstract 0422, 2001.