Rajiv Gandhi University of Health Sciences, Karnataka ,Bangalore s36

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA,BANGALORE

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1.NAME OF THE CANDIDATE DR.NALINI B WAGMODE AND ADDRESS (IN BLOCK #679-A,1 ST MAIN ROAD, LETTERS) T.DASARAHALLI, BANGALORE-560057 2.NAME OF INSTITUTION BANGALORE MEDICAL COLLEGE AND RESEARCH INSTITUTE,BANGALORE 3.COURSE OF STUDY AND M.D.GENERAL MEDICINE SUBJECT 4.DATE OF ADMISSION TO 4th JUNE 2010 COURSE 5.TITLE OF TOPIC A PROSPECTIVE STUDY OF PATIENTS INITIATED ON SECOND LINE ANTIRETROVIRAL THERAPY-CLINICAL PROFILE AND SIDE EFFECTS 6. BRIEF RESUME OF THE INTENDED WORK

6.1Need for the Study:

HIV infection/AIDS is pandemic, with cases reported from nearly every country in the world. Unlike other epidemics, AIDS falls most heavily on young adults in their prime, posing a grave challenge in the areas of health, social and economic development. In India, the National AIDS Control Programme (NACP) has been operational since 1987. For its effective implementation, a National AIDS Control Organization has been set up.

Combination antiretroviral therapy (ART), or highly active antiretroviral therapy (HAART), is the cornerstone of management of patients with HIV infection. Following the initiation of widespread use of HAART, marked declines have been noted in the incidence of most AIDS-defining conditions. Suppression of HIV replication is an important component in prolonging life as well as in improving the quality of life in patients with HIV infection1.

Greater knowledge of viral dynamics through the use of viral load and resistance testing has made clear that combination therapy with maximally efficacious and potent agents will reduce viral replication to the lowest possible level and decrease the likelihood of emergence of resistance. Thus, administration of highly active antiretroviral therapy (HAART), typically comprising a combination of 3-4 antiretroviral agents, has become the standard of care2. Second line ART acts as a boon for the very existence of birth (Live/Life) amid the HIV/AIDS patients. There has been limited research on second line ART and its side effects in India, hence this study has been taken up. 6.2Review of Literature:

A study conducted by Bankim Mankad et al3 concluded that switching to second line ART based on Immunological Failure, Clinical Failure is not recommended; as out of 122 PLHAs analyzed only 75 PLHAs have Virological Failure. Adherence Counseling for 2nd Line ART helps quite in reduction of PVL. Deaths analysis shows that late switch to 2nd Line ART at CD4 < 100 cells/mm3 may not result in desired therapeutic goals.

Retrospective Study by Malladi et al4, conclusions drawn were as follows: of 1260 patients on ART 68 developed side effects, most common side effect being GI intolerance

A study by Pujades-Rodriguez et al5 concluded that the rate of switch to second-line treatment in antiretroviral therapy-naive adults on non- nucleoside reverse transcriptase inhibitor-based first-line antiretroviral therapy was relatively low, with good early outcomes observed in protease inhibitor-based second-line regimens. Severe immunosuppression was associated with increased mortality on second-line treatment.

A Study by Katherine V. Heath et al6 50% appeared to have probable lipodystrophy, with 36% reporting peripheral wasting, 33% abdominal weight gain, 6% buffalo hump, and 10 and 12% increased triglyceride or cholesterol levels, respectively.

6.3 Aims and Objectives:

To study the clinical profile of patients on second line ART

To study the side effect profile of second line ART drugs and relation of immunosupression with mortality 7. Materials and Methods:

7.1Source of data:

The study will be conducted at Department of Medicine, BMC&RI,

Bowring and lady Curzon hospitals from Oct 2010 to Sept 2012.

The cohort will include patients failing First line ART as per defined by NACO & WHO guidelines being switched to second line ART at our centre during this period

7.2. Method of collection of data:

After taking informed consent patients will be admitted. History, examination, WHO clinical staging, CD4 count, viral load, baseline investigations including CBC, RFT, LFT, fasting lipid profile, FBS, PPBS will be carried out. Patients registered for second line ART at our centre will be monitored for early toxicity during their hospital admission and then followed up at regular intervals of 3,6,12 months with the above parameters.

7.3 Inclusion Criteria:

Patients failing First line ART as per defined by NACO guidelines being switched to second line ART at our Centre.

7.4 Exclusion Criteria: 1) Patient not registered at a Government ART centre

2) Patient who do not give consent for the study

7.5 Study design: A cohort (prospective) study.

SAMPLE SIZE:A total of 50 cases will be followed up over a period of 1year study with respect to WHO clinical staging, CD4 count, Lab parameters at baseline & next 3, 6mts, 12mts 7.6 .Statistical methods:

Analysis of variance (ANOVA)-Z test and appropriate statistical tools.

7.7 Does the study require any investigations or interventions to be conducted on patients?

1. Complete hemogram

2. Liver function tests

3. Renal function tests

4. Fasting blood sugar

5. Fasting lipid profile

6. Viral load

7. CD4 Count

7.8.Has ethical clearance been obtained from your institution in case of 7.7?

YES 8. LIST OF REFERENCES

1)Anthony S.Fauci, H. Clifford Lane. Human Immunodeficiency Virus disease:AIDS and related disorders. In:Anthony S.Fauci, Dennis L Kasper, Dan L Longo, Eugene Braunwald, Stephen L. Hauser, J.Larey Jameson et al, editors. Harrison’ s Principles of Internal Medicine. 17th ed. NewYork:McGraw Hill; 2008: p1190.

2)Sharon Safrin. Antiretroviral agents. In:Bertram G. Katzung, editor. Basic and clinical pharmacology. 10th ed. USA:McGraw Hill;2007:p853

3) Bankim Mankad, Hemang Purohit, Asha Shah, Manoj Shevkani, Burzin Kavina,et al. Our experience in second line Anti Retroviral Therapy (ART) At State Aids Clinical Expert Panel (SACEP)clinic. Retrovirology 2010;7;53

4) Malladi V S S, Chandra N, Rao M N, Raju Y S. Side effects of Anti Retroviral Drugs – Experience of a tertiary care hospital. JAPI 2009;59

5) Pujades-Rodríguez Mar, O'Brien Daniel, Humblet Pierre,Calmy Alexandra. Second-line antiretroviral therapy in resource-limited settings: the experience of Medecins Sans Frontieres AIDS 2008;22;1305-1312

6)Heath Katherine V, Hogg Robert S, Chan Keith J, Harris Marianne, Montessori Valerie, et al. Lipodystrophy-associated morphological, cholesterol and triglyceride abnormalities in a population-based HIV/AIDS treatment database. AIDS:2001;15;231-239

7)Friis-Moller N. Class of antiretroviral drugs and the risk of myocardial infarction. New England Journal of medicine.2007;356;1723-1735.

8)Behrens G. Dejam A, Schmidt H. Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. AIDS 1999, 13;63-70

9)Carr A, Samaras K, Thorisdottir A. Diagnosis, prediction, an natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia and diabetes mellitus: a cohort study. Lancet 1999; 353;2093-2099. 9. SIGNATURE OF THE CANDIDATE

Dr. NALINI B WAGMODE 10. REMARKS OF THE GUIDE ART programme in Government of Karnataka was started in 2004 through National AIDS Control Organisation and Karnataka State AIDS Prevention Society. During follow up,many patients have developed toxicity and failure to the First line drugs. In 2008 NACO identified B&LCH as centre of excellence in Karnataka in which Second line drugs are provided to patients all over state free of cost. Since there is no alternative to Second line failure,this study is taken up to know the clinical profile and side effects of patients on Second line ART.

11. 1 NAME AND DESIGNATION Dr. PRABHAKAR B OF GUIDE M.D. PROFESSOR OF MEDICINE BMC & RI, BANGALORE 11.2 SIGNATURE 11.3. CO-GUIDE(if any)

11.4.SIGNATURE

11.5. HEAD OF THE Dr. VASANTHA KAMATH DEPARTMENT M.D.,F.I.C.P. PROF. AND HOD OF MEDICINE BMC & RI, BANGALORE 11.6. SIGNATURE

12.1 REMARKS OF THE CHAIRMAN AND PRINCIPAL

12.2 SIGNATURE