The Power of PEPFAR

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Dr. Emily Erbelding, left, speaks on the Power of PEPFAR at IDSA 2010

AIDS mortality in South Africa has seen an observed decrease at the population level from 2006-09 — the first time since the epidemic began, according to Jeffrey Klausner, MD, of the Centers for Disease Control and Prevention (CDC) in Pretoria. He presented on the impact of the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) in South Africa at the 48th Annual Meeting of the Infectious Diseases Society of America in Vancouver Thursday.

“It’s quite impressive that we can see this level of impact and we expect to see this improvement in life expectancy to continue,” Klausner said. This was just one example Klausner gave of the “Power of PEPFAR,” as he moderated and presented at a session by that name. Klausner said the implementation of PEPFAR in South Africa has been associated with significant increases in HIV treatment and services, reduced mortality and increased life expectancy.

High-functioning prevention of mother to child transmission (PMTCT) programs are preventing a substantial number of HIV infected babies in the country. Dr. Klausner reported that from April to June 2010, 92 percent of women reporting for prenatal services agreed to be tested for HIV, with 28 percent of those testing HIV-positive. Ninety-five percent of those women were initiated on antiretroviral prophylaxis. It is estimated that through the effective use of PMTCT, more than 61,000 infants per year in South Africa are protected from HIV infection.

While the strides have been significant, much more needs to be done, Klausner said. Accelerated prevention programs in other areas, including male circumcision, are needed to help curb the epidemic. Trials show that initiation of highly active antiretroviral therapy (HAART) at higher CD4 counts and switching to tenofovir-based treatment regimens improve survival rates significantly. But the resources needed to start antiretroviral therapy (ART) earlier are not there, and there is still no fixed-dose combination therapy available in South Africa, Klausner said.

Despite the World Health Organization recommendation that ART for HIV-infected people begin at CD4 counts of 350, the majority of HIV-infected people in South Africa are starting therapy at CD4 counts of 200. “Less than 40 percent of those in need as defined by the WHO are on treatment,” Klausner said. Current treatment guidelines in South Africa provide for initiation of ART for pregnant mothers and patients with TB at CD4 cell counts of 350 or fewer.

Today there are 1.1 million PEPFAR-supported patients on ART in South Africa, the South African government currently predicts they are treating 70 percent of those with CD4 counts less than 200; the goal is to expand that to at least 80 percent by the end of 2011.  

Cotrimoxazole saves lives

Jonathan Kaplan with the Division of Global AIDS at the CDC presented about HIV-related opportunistic infections in the African context.  He highlighted cotrimoxazole (CTX) as a lifesaving prophylaxis antibiotic, which offers substantial protection against a variety of bacterial infections, pneumonia, malaria, diarrhea and sinusitis.  Studies have demonstrated that CTX provides a benefit even to patients on ART, and reduces the risk of malaria by 90 percent with the benefit increasing even further by providing patients with ART and insecticide-treated bed nets.  Research has also indicated that patients on CTX also have reduced rates of CD4 cell decline. And in a study in Zambia reported in the Lancet in 2004, CTX reduced hospitalization by 23 percent and death by 43 percent in children.

The leading cause of death for persons with HIV is tuberculosis.  Isoniazid preventive therapy (IPT) has been demonstrated to reduce the risk of TB disease by as much as 62 percent.  Despite the fact that WHO has been recommending IPT for more than a decade, coverage rates remain extraordinarily low.  There are some outstanding questions about the length of time patients should be on isoniazid (INH) – especially in TB endemic areas.  A Botswana study found a strong protective benefit when INH was continued for 36 months.  Current WHO guidelines recommend a 6-month course.

Kaplan identified cryptoccocal meningitis as a serious opportunistic infection with high mortality that should be prioritized for further research related to screening and treatment.

The current PEPFAR preventative care package includes cotrimoxazole prophylaxis, safe water, insecticide- treated bed nets, TB screening and a nutritional assessment.  Important goals in the arena of HIV care include increasing coverage and adherence to CTX, completion of IPT and the retention of pre-ART patients in care.

NIAID and PEPFAR Partner on Research Priorities 

Emily Erbelding, Deputy Director of the Division of AIDS at the National Institute of AIDS and Infectious Diseases (NIAID) highlighted some PEPFAR-related research priorities.  She identified tuberculosis as the highest PEPFAR-related clinical research priority since the “full benefits of ART rollout cannot be achieved without improvements in TB diagnosis and treatment, and TB control will not be successful without widespread and successful HIV treatment.”  In fact Erbelding called tuberculosis the “highest clinical trial priority in the Division of AIDS.”

Erbelding highlighted the need for a range of new diagnostic tools for resource poor settings such as diagnostics to measure HIV RNA, CD4 cells, HIV drug resistance as well as new TB and malaria diagnostics and a test to measure HIV seroincidence—so that the impact of new prevention interventions can be calculated.

Dr. Emily Erbelding shows the audience at IDSA 2010 a map of HIV/AIDS clinical research sites.

Erbelding also noted that implementation science to address the gap between science and practice was critically important and posed a number of research questions in this arena.

  • How can nutritional packages improve HIV prevention, care and treatment outcomes?
  • How can we eliminate bottlenecks in PMTCT services?
  • How can we best bring male circumcision to scale?
  • What behavioral prevention approaches are components of effective combination packages?
  • What innovative strategies strengthen health systems to improve HIV outcomes?

National Institutes of Health/PEPFAR implementation science initiatives under consideration are available online.

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