Debates about whether to start treatment at a CD4 count of 350 in developing countries ignore the fact that current programmes are doing very badly at retaining patients in care after diagnosis or starting people on treatment before they become seriously ill, Dr Francois Venter, President of the South African HIV Clinicians Society told the Fifth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention on Monday.
Speaking during a conference symposium on when to start treatment, Dr Venter pointed out that the current average CD4 count at which patients start treatment in South Africa is 87 cells/mm3.
Despite a huge increase in the number of people who undergo HIV testing – up to one-quarter of South African adults took a test in the past year, according to 2009 research by the Human Sciences Research Council – the average CD4 count at which patients in his Johannesburg clinic start treatment has not moved above 80 to 100 cells since 2004, Dr Venter said.
“We are still doing a terrible job of retaining patients in care, and we need to start looking harder at retention in care,” he said. “Are you delivered into a package of care that looks after you [after diagnosis]?” he asked.
A large number of patients were dying while waiting for the results of diagnostic tests and while undergoing treatment-preparation counselling, or during acute opportunistic infections.
“Around half of patients in my practice start antiretroviral treatment during or just after treatment of an acute OI,” said Dr Venter, but clinicians still lack definitive information about the most appropriate time to start antiretroviral treatment in conditions such as cryptococcosis, the second most common opportunistic infection in southern Africa, and there is limited awareness of data from the recently halted SAPIT trial, which shows that antiretroviral treatment should not be delayed in TB patients until the completion of the TB treatment course.
He also expressed concern about the implications of recent findings on the inflammatory effects of HIV infection for developing countries. “Cardiovascular disease is not usually seen as an African problem, but death-certificate analysis in South Africa recently revealed that diabetes and hypertension were among the most frequent causes of death.”
Similarly, South Africa is seeing overlapping epidemics of HIV and obesity. Potent cardiovascular risks may lead to a high rate of cardiovascular disease in people with HIV, Dr Venter argued. He also drew attention to the high rate of liver disease and hepatitis virus infection in the developing world, to data showing that uncontrolled HIV replication exacerbates liver damage, and to the high frequency of kidney disease in African-Americans with advanced HIV infection (people of African origin appear to have a high risk of HIV-associated kidney damage).
“The thing that filled me with fear [looking at the data on inflammation and HIV] was renal disease. Kidney transplants, dialysis, even prophylactic drugs to deal with proteinuria are difficult to obtain and expensive in this region.”
However, the priority group for earlier treatment is pregnant women, said Dr Venter. “Treating mothers is much easier than treating children”, although implementation challenges such as defining the best antiretroviral regimen for use in pregnant women remain.
Eighty-four per cent of maternal deaths and 47% of postnatal infant infections occur at CD4 counts below 350, he noted.
“We could meet the Millenium Development Goal 5 on reducing maternal mortality by raising the threshold to 350 for pregnant women.”
However, one of the major obstacles to early treatment in the developing world is the current reliance on d4T (stavudine) in first-line treatment.
Dr Venter said that when he conducted an informal survey of colleagues treating large number of patients on when they would choose to start treatment, significant reservations about earlier treatment using d4T were expressed.
At a satellite meeting organised by Médecins sans Frontières, Dr Venter warned that activist demands for the better-tolerated drug tenofovir (Viread) to replace d4T in South Africa’s first-line regimen needed to be considered in the light of poor progress towards delivering treatment to those in urgent need. “A lot of our patients are dying without even having access to d4T.” He also warned that South Africa’s national treatment programme “is pretty much committed to staying with d4T for the next three to four years”.
He called for prospective research to quantify the effects of lower doses of d4T in the region, and Dr Graeme Meintjes of GF Jooste Hospital in Cape Town told the satellite meeting that the incidence of lactic acidosis and hyperlactataemia had fallen dramatically since the adoption of a 30mg adult dose of d4T in 2006.