Despite the increasing access to lower cost generic High Active Antiretroviral Therapeutic (HAART) Regimens and significant decrease in HIV-related morbidity and mortality, even less expensive and more tolerable first-line regimens are needed to achieve better treatment outcomes, asserts a clinical study.

The study, probing the reasons for modification of generic HAART regimens among patients in southern Asia, conducted by a group of scientists at YRG Centre for AIDS Research and Education (YRG CARE), Chennai, manifested that the least expensive generic HAART first-line regimen, stavudine (d4T) plus lamivudine (3TC) plus Nevirapine (NVP), is continued to be widely used in resource-constrained settings, despite of its high incidents of d4T related toxicities including lipoatrophy and peripheral neuropathy, due to its low cost.

More than 80% of the patients in the cohort were under NVP-containing regimens, which are also known to have a significant risk of causing hepatotoxicity. The study suggests that efforts should be made to replace d4T with alternative affordable drugs.

In the total number of 6821 patients registered at YRG CARE in 1996-2004, 3736 patients were in need of therapy. By the WHO criteria 1443 patients were previously Anti Retroviral Therapeutic (ART) naïve, initiated triple HAART, and had at least one follow-up visit at the centre. Among these 1443 patients, almost 9% discontinued therapy after approximately 4 months. In this, 64% of the patients discontinued this first-line regimen due to the unaffordability of the cost of treatment. 21% patients, in this 1443, withdrew from the treatment due to adverse events (AE), mainly itching or skin rash and hepatotoxicity and 1.6% due to treatment failure.

The study revealed that more than half the patients who needed ART according to WHO guidelines had initiated therapy by 2004 in stark contrast with the rate of 8.2% of patients initiated therapy between 1996 and 1999. The change should be attributed to the introduction of generic ART at a lower cost in the year 2000, added the scholars.

Though the number of patients who undergo therapy has increased, the result does not reach the success rate, as most of them discontinue the therapy at the first-line regimen itself. Even if some of these patients may restart treatment when their financial situation is improved, the second and third line regimens would be much expensive. The inconsistent therapy can be harmful and can put the patient at risk for developing resistance to the less expensive regimens.

Switching over from one regimen to another due to the AE or treatment failure in India has been identified only after the occurrence of an opportunistic infection and 70% switched after a decline in CD4 cell count, while in foreign countries, it is identified as the result of an unsuppressed viral load. The cost of monitoring viral load makes it an expensive analysing method, which most of the patients cannot afford.

Most of the patients substituted therapy because of toxicities and the most frequently used NVP containing regiments, although less expensive, were more likely to be associated with toxicities, mentions the study.

"This study will be helpful for drug researchers and companies to realise the need of a less expensive more tolerable first-line regimens in the Indian market," said Dr.N.Kumrasamy, chief medical officer and clinical researcher, YRG CARE, who played a key role in the study. He added that cost-effective treatment monitoring tools are also needed to achieve better treatment outcomes and improve access in resource-constrained settings.

Dr. Suniti Solomon, Dr. Anitha. J. Cecila, Dr. T. Yepthomi, Dr. P. Balakrishnan and Dr. Suneeta Saghayam from YRG CARE and Dr. S. Vallabhaneni, Dr. Timothy P. Flanigan, Dr. Chales C.J. Carpenter and Dr. Kenneth H. Mayer from The Miriam Hospital, Brown University, Providence, Rhode Island participated in the study.