July 21, 2009
Landmark Five-Year African Study Indicates That HIV Therapy May Be Given Safely in Resource-Limited Settings Without Routine Laboratory Monitoring
DART, which was sponsored by the United Kingdom’s
“The DART study provides important additional clinical evidence that HIV
treatment utilizing Viread helps to extend life in developing countries
where the AIDS pandemic has hit the hardest,” said
About the DART Study
DART was a five-year, open-label, randomized trial among 3,316
treatment-naïve adults with advanced HIV disease in
Seventy-four percent of patients received a combination regimen of Viread with lamivudine/zidovudine. Sixteen percent of patients received nevirapine/lamivudine/zidovudine and nine percent of patients received abacavir/lamivudine/zidovudine.
Exclusion criteria for DART enrollment included creatinine levels of more than 360 μmol/l (4.1 mg/dl) and/or urea levels of more than five times the upper limit of normal. Sixty-five percent of patients in the DART trial were female and the median age of trial participants was 37 (18-73). The median CD4 cell count was 86 cells/mm3.
Among patients whose doctors received regular laboratory test results, the survival rate after five years was 90 percent. Among patients whose doctors relied on clinical assessments alone, the survival rate similarly was 87 percent. No difference in the occurrence of drug-related side effects was seen between the two groups.
DART researchers also examined various measures of drug safety, including the effect of HIV medicines on kidney function. At baseline, 52 percent of DART trial participants had impaired renal function upon enrollment, defined as having an estimated glomerular filtration rate (eGFR) of less than 90 ml/min/1.73m2. In addition, researchers evaluated the presence of chronic kidney disease (CKD) using two defining criteria: The first defined CKD as GFR of less than 60 ml/min/1.73m2 present on at least two occasions for more than three months, or a 25 percent drop in GFR for patients whose GFR was already less than 60 ml/min/1.73m2 at baseline. The second definition characterized CKD as being present among any patient who experienced a 25 percent drop in GFR from baseline.
After 216 weeks of treatment, a severe decrease in GFR to less than 30 ml/min/1.73m2 was observed infrequently in DART participants receiving Viread. Severe GFR decreases were seen in 3.1 percent of participants on a Viread-based regimen, compared to 2.4 percent and 1.9 percent of patients receiving study regimens based on the drugs abacavir and nevirapine, respectively, which was not statistically significant. CKD was slightly more common among patients receiving a Viread-based regimen. Depending on the defining criteria used, either 3.4 percent or 5.9 percent of patients receiving Viread experienced CKD during the study, compared to 2.1 percent or 3.1 percent of patients receiving an abacavir-based regimen, and 1.1 percent or 2.1 percent of patients receiving a nevirapine-based regimen. Severe decreases in GFR or CKD were infrequent among DART participants regardless of whether laboratory testing was provided and regardless of patients’ treatment regimens.
Renal disease contributed to 16 deaths during DART. Most of these cases also involved other HIV-related illnesses. Only two deaths were definitely or probably related to antiretroviral therapy that included Viread. Three other deaths involved patients who had severely decreased GFR at baseline, all of whom received Viread as part of their treatment regimen.
Viread and Truvada® (emtricitabine and tenofovir disoproxil
fumarate) are recommended as first- and second-line antiretroviral
The parent compound of Viread was discovered through a collaborative
research effort between Dr.
The recommended dose for the treatment of HIV is 300 mg once daily taken orally without regard to food. The dosing interval of Viread should be adjusted in patients with renal impairment.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including Viread, in combination with other antiretrovirals.
Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including Viread. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including Viread. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
New onset or worsening of renal impairment including cases of acute renal failure and Fanconi syndrome has been reported with the use of Viread. It is recommended to assess creatinine clearance (CrCl) before initiating treatment with Viread and monitor CrCl and serum phosphorus in patients at risk. Administering Viread with concurrent or recent use of nephrotoxic drugs should be avoided. Viread should not be administered in combination with Hepsera® (adefovir dipivoxil).
Viread should only be used as part of an appropriate antiretroviral combination regimen in HIV-infected patients with or without HBV coinfection. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with Viread.
Decreases in bone mineral density (BMD) have been observed in HIV-infected patients. It is recommended that BMD monitoring be considered for patients with a history of pathologic fracture or who are at risk for osteopenia. The bone effects of Viread have not been studied in patients with chronic HBV infection.
Redistribution/accumulation of body fat has been observed in HIV-infected patients receiving antiretroviral combination therapy.
Immune reconstitution syndrome has been observed in HIV-infected patients receiving antiretroviral combination therapy, including Viread, which may necessitate further evaluation and treatment.
Early virologic failure has been reported in HIV-infected patients on triple nucleoside-only regimens. Patients on a therapy utilizing a triple nucleoside-only regimen should be carefully monitored and considered for treatment modification.
U.S. full prescribing information for Viread is available at www.Viread.com.
U.S. full prescribing information for Truvada is available at www.Truvada.com.
U.S. full prescribing information for Hepsera is available at www.Hepsera.com.
U.S. full prescribing information for Atripla is available at www.Atripla.com.
Viread, Hepsera and Truvada are registered trademarks of
Atripla is a registered trademark of
For more information on
Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Erin Rau, 650-522-5635 (Media)