HAART regimens including generic efavirenz provide effective suppression of viral load, increase CD4 cell counts, and are safe and well tolerated, according to a study conducted in southern India and published in the April 8th edition of AIDS. The investigators write that the results of their study “are comparable to findings in clinical trials and prospective studies on proprietary efavirenz.”
The World Health Organisation recommends the use of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens as first line treatment for HIV-positive individuals in resource limited settings. Earlier studies have shown these regimens to be safe, well tolerated and able to increase CD4 cell count. However, there are few data on the effect of generic efavirenz on viral load.
Investigators from the YRG Centre for AIDS Research and Education, a non-profit organisation providing HIV treatment to 7000 individuals in southern India and Brown University in the US therefore conducted a study to determine the ability of generic efavirenz to suppress HIV viral load.
A total of 40 treatment-naïve individuals were included in the study. All were aged over 18 year. At baseline the median CD4 cell count was 164 cells/mm3 and median viral load was 259,000 copies/ml.
Treatment with generic antiretrovirals manufactured by the Indian pharmaceutical company Cipla was provided. All patients were given generic efavirenz in combination with either generic AZT and 3TC (18 individuals), or if an individual had anaemia, generic d4T and 3TC (22 individuals).
After three and six months of treatment individuals had their viral load and CD4 cell count measured. Data on side-effects and cholesterol were also gathered.
The primary endpoint of the study was the proportion of patients with a viral load below 400 copies/ml after six months of treatment. Secondary endpoints included the three and six month increases in CD4 cell, the incidence of new opportunistic infections, treatment-related side-effects, lipid abnormalities, and treatment changes.
After six months of generic efavirenz-based HAART, 95% (38 of 40 patients) had a viral load below 400 copies/ml. One of the patients who did not achieve viral suppression was not adherent to therapy and the investigators postulate that the other individual may have been infected with resistant virus at baseline.
CD4 cell count increased significantly from baseline to 304 cells/mm3 (p 3 (p
No new AIDS-defining illnesses were reported. One patient switched from efavirenz to nelfinavir because of facial swelling after twelve weeks, and another individual switched from efavirenz to nelfinavir after 22 weeks after becaming pregnant.
After six months, significant increases in HDL cholesterol, LDL cholesterol, and total cholesterol had been observed (all p
Dizziness was the most commonly reported side-effect related to efavirenz (15 patients, 35%), and sleep disturbances were reported by three individuals (8%). Vomiting and diarrhoea were experienced by seven patients (18%).
“This study clearly supports the theory that generic NNRTI-based regimens are effective at suppressing the plasma viral load and increasing the CD4 cell count after six months of therapy”, write the investigators, adding “our results are comparable to findings in clinical trials and prospective studies on proprietary efavirenz.”
The small size of the study population is acknowledged by the investigators as a possible limitation of their research. Nevertheless they conclude, “in this cohort, generic-efavirenz-based regimens were safe and effective at suppressing viral load, while increasing the CD4…count. These data add to the growing body of knowledge supporting the use of generic HAART in resource limited settings.”
Nagalingeswaran K et al. Rapid viral load suppression following generic highly active antiretroviral therapy in Southern Indian HIV-infected patients. AIDS 19: 625 – 632, 2005.