New data released by the international medical humanitarian organization Médecins Sans Frontières (MSF) at the 14th Conference on Retroviruses and Opportunistic Infections (CROI) in Los Angeles this week demonstrates good clinical outcomes for second-line antiretroviral therapy (ART) in resource-poor settings.
Newer medicines needed for second-line regimens, however, remain unaffordable and largely unavailable in affected countries, and adapted diagnostic tools needed to appropriately monitor lifelong treatment are missing.
MSF presented a study of 352 adult patients from 50 MSF-supported ART projects in 22 countries who had been on first-line treatment for at least six months and then needed to switch to a second-line regimen either because of a drop in CD4 count or a clinical event. The second-line regimen included a new drug class, a protease inhibitor, and at least one change in the nucleoside component. The median follow-up period was seven months. Overall probability of survival was 86 per cent at 12 months, and median CD4 gain +131 at 12 months.
"Our outcomes tell us that second-line AIDS therapy is working for people living with AIDS in resource-poor settings," said Dr. Alexandra Calmy, HIV/AIDS Advisor at Médecins Sans Frontières Campaign for Access to Essential Medicines, speaking at a press conference at CROI. "This despite several obstacles, like the lack of access to the best regimens and the fact that patients tend to go on second line late in the course of the disease."
According to the MSF study, there was a switch rate to second-line treatment of 4.4/1,000 patients per year, indicating that patients in resource-poor settings tended to stay on a first-line regimen much longer than in developed countries.
"Patients might die before they even get a chance to switch to a second-line regimen," Dr. Calmy added. "We simply lack the diagnostic tools to efficiently diagnose treatment failure early enough. And doctors are reluctant to switch to second line because it is the last therapeutic option and they are afraid to burn the two treatment lines available by switching patients unnecessarily."
While the needs for a second-line regimen are likely to increase in the coming years, medicines used for second-line therapy are mostly unavailable or unaffordable in developing countries. For example, the heat-stable form of the boosted protease-inhibitor lopinavir/ritonavir, marketed as Kaletra by Abbott Laboratories, is only sold in high-income countries [US, Europe, Australia] because Abbott has taken few steps to make it available in any resource-poor country except South Africa.
The company's price for middle-income countries such as Thailand is unacceptably high. The technology required to monitor the viral load in patients' blood is also extremely expensive and not very accessible in developing countries. Without viral load testing, determining the moment at which patients need to be switched to a newer regimen is difficult and relying on clinical symptoms or immunological failure is often too late.
MSF currently provides ART to more than 80,000 patients in over 30 countries. In one MSF project in Khayelitsha, South Africa, where regular monitoring with viral load testing is available, 20 per cent of people needed to be switched to a second-line regimen after being on treatment for five years, according to data presented at CROI by Dr. Gilles van Cutsem, from MSF in South Africa.
"We need newer medicines and viral load tests rapidly and at a large-scale because we know that we're going to be seeing a growing number of people who need to switch regimens in our projects," said Dr. Laurent Ferradini, also of MSF, who presented the first study based on virological indicators on the efficacy of second-line ART in Cambodia. "But the medicines we now use in second-line regimens are used as a final, salvage-therapy option. What will we do once people start to again fail on this regimen?"
Regimens that consist of newer medicines can cost between 10 and 50 times more than today's standard first-line therapy. Beyond price, many newer medicines are marketed under monopoly-like conditions, as was the case for first-line drugs in the late 1990s.
Competition among multiple manufacturers, including generic producers is what helped bring prices of first-line therapy down by 99% and increase availability. But due to increased patenting in key generics producing countries such as India, sources of affordable medicines are increasingly drying up.