Resistance to anti-HIV drugs in Uganda developed due to drug supply problems

Some HIV-infected patients in Uganda who self-paid for their antiretroviral medications experienced interruptions in drug supply due to either financial demands or supply logistical disruptions.

These treatment interruptions led to the development of resistance to antiretroviral medications in patients.

These findings by a team led by researchers at the Infectious Diseases Institute at Makerere University, Kampala, and UCSF are reported in the April 22, 2007 issue of the journal "AIDS."

"We have found the concern is not about the occasional missed dose, most of the patients had near perfect adherence and full suppression of the virus, but about supply interruptions that led to longer multi-day treatment interruptions allowing resistance to develop," said study lead author Jessica Oyugi, MD, from the Infectious Diseases Institute at Makerere University, Kampala, Uganda.

The study followed just under 100 patients who self paid for generic fixed-dose antiretroviral formulations. Findings showed that medications were very effective at suppressing the virus, with full viral suppression in over 80 percent of people on treatment for 6 months. Resistance developed in people during treatment interruptions, and 90 percent of all missed doses were due to treatment interruptions as opposed to the occasional skipped dose. Further, almost 50 percent of the participants interrupted treatment due to financial difficulties. In addition, at one point during the study period, supply of one product was halted due to customs issues. A two-week nationwide shortage resulted that created gaps in treatment for some individuals taking that medication.

"In a context where the ability of poor people to adhere to medications regimens has been questioned, the issue is not so much about behavioral strategies to increase adherence, but about structural failures that interrupt access to treatment. Free access to treatment leads to better survival than self-pay therapy because free treatment may be less susceptible to interruptions that lead to resistance" said study senior author David R. Bangsberg, MD, MPH, director of the UCSF Epidemiology and Prevention Interventions Center at San Francisco General Hospital.

The climate in Uganda has changed since the study took place between September 2002 and April 2004. At that time, most patients paid for antiretroviral therapy. Today, most HIV patients are receiving drugs supplied for free by either PEPFAR, the U.S. President's Emergency Plan for AIDS Relief, a five-year, $15-billion, multifaceted approach to combating HIV/AIDS around the world, or The Global Fund to Fight AIDS, Tuberculosis and Malaria, which was created to dramatically increase resources to fight three of the world's most devastating diseases, and to direct those resources to areas of greatest need.

"Notwithstanding the current programs providing free antiretrovirals, these findings do highlight the need for strong logistics and drug supply management in any antiretroviral therapy program as well as continued monitoring of adherence. While our patients did a great job of taking their medications as directed when they were affordable and available, their overall adherence did wane a bit over the study period," said Oyugi.