Treatment Models from India
Interview with Shashank Joshi, M.D.
March 17, 2000
Shashank R. Joshi, M.D., president of the HOPE Foundation in Mumbai, India, is an HIV specialist in a public hospital system with more than 36,000 patients with HIV; in addition, he follows over 500 HIV patients in his private practice, and more than 180 HIV-discordant couples. We asked Dr. Joshi to share information and experiences that might be useful to physicians or patients elsewhere.
An Evolving Standard of Care in India
AIDS Treatment News: How to you approach HIV care in India, where few patients have access to triple-drug combination antiretroviral treatment?
Dr. Joshi: We are developing low-cost treatment models in the Indian population, because of the high cost of antiretroviral drugs.
A few of my private patients can afford some triple therapy with a protease inhibitor and two nucleoside analogs, but not continuously. So for some patients, we suggested triple therapy on alternate months, one month on a HAART combination and the next month without antiretrovirals. At the end of a year we have a small cohort of 26 patients who have done very well on this treatment; all of them have undetectable viral load -- below 20 copies on the Roche Ultrasensitive test -- and their average CD4 count has improved. It is important to note that all of these patients started this regimen with a CD4 count over 300. NIH is critically looking at this cohort. We are now trying to validate these results, and are working with other researchers, including in the U.S.
We are looking at other low-cost models as well. We do not have ddI in India, so often I use d4T, 3TC, and hydroxyurea, in an antiretroviral-naive population. [Note: Hydroxyurea, an inexpensive drug usually used in cancer treatment, may improve the activity of certain antiretrovirals, especially ddI -- but can also increase the toxicity of the regimen.] This combination is working very well in a small but significant number of cases, reducing viral load and inducing CTL responses. Significantly, we have had no mitochondrial toxicity in these patients -- perhaps because we are giving them appropriate immunonutrition, including multivitamins, antioxidants, and certain other micronutrients. This nutritional therapy may be particularly important in the Indian population, because wasting is a major problem. [Note: Some researchers believe that mitochondrial toxicity -- a condition recognized elsewhere in medicine -- may caused by nucleoside analog drugs -- and may be responsible for much of their toxicity, as well as some but not all of the body-shape changes often attributed to protease inhibitors.]
We are planning to study the product ImmunoCal, a nutritional supplement derived from whey protein, as a source of glutathione. It is believed that mitochondrial toxicity, which the nucleoside analog drugs and hydroxyurea may have, is mediated through the glutathione pathway. If you give patients a natural source of glutathione, maybe this problem can be prevented, and you may not see the liver toxicity, lactic acidosis, or other problems which might otherwise occur. We want to see if improved nutrition can improve the catabolic cachexia [wasting], and also we want to look for any antiretroviral effect. I understand that a small but significant number of patients has dropped their viral load by a log, after treatment with nutritional regimens designed to support the immune system.
So an evolving standard of care in India is that we offer patients antiretroviral therapy with two nucleoside analogs and a protease inhibitor; if they cannot afford that, they can try structured treatment interruption, one month on and one month off of the triple therapy; if they cannot afford that, we look into an option like d4T and 3TC and hydroxyurea. In any case, treatment includes multivitamins and antioxidant supplements, psychological support, and meditation and yoga.
Our protocol always includes vitamin E and vitamin C. We try to get the vitamin E from natural sources; we do not use the synthetic pills because they are derived from petrochemical intermediates, and some believe that these preparations might be pro-oxidant as well as antioxidant. So we use extracts from wheat germ, usually 200 IU to 400 IU. We also include B-complex vitamins, selenium, and other minerals.
Herbal Treatments for Antiretroviral or IL-2 Effects
Dr. Joshi: We are also using certain herbal medications -- some of which increase the body's natural production of IL-2. We presented a poster on this approach in 1998, at the 12th World AIDS Conference in Geneva ["Effect of unique herbal formulation in Indian HIV patients: A pilot study," 12th World AIDS Conference, Geneva, June 28 - July 3, 1998, abstract #42385]. We have compiled an herbal booklet, listing each ingredient, with references to studies showing antiviral activity, or increases in the natural production of IL-2.
De-Worming, and Other Treatment for Intestinal Inflammation
Dr. Joshi: We are also giving a weekly dose of albendazole to patients who have intestinal parasites. We have seen that if we de-worm patients routinely, after six months to a year there is a reduction of viral load. Indian patients traditionally have higher viral set points than European patients; this might be related to the parasites. De-worming might assist mucosal immunity in the gut, and improve the CTL response against HIV. Also, in a couple of patients, I am trying mesalamine, a drug used to reduce intestinal inflammation.
Side Effects of Antiretroviral Regimens
Dr. Joshi: We have not had problems with mitochondrial toxicity -- perhaps because of our nutritional therapy, or perhaps because we do not have ddI in India. I also believe that immunonutrition helps to some extent with lipodystrophy.
But we are seeing lipodystrophy. And we are also seeing other side effects which have been reported elsewhere, including osteoporosis, and aseptic necrosis of the femur, in people on protease-inhibitor regimens in India. So there is considerable concern about these drugs, and we are looking at PI-sparing regimens. Nevirapine is now available in India, and we will be using it for this purpose.
Copyright 2000 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.
This article was provided by AIDS Treatment News. It is a part of the publication AIDS Treatment News.