Tenofovir Based First Line Therapy in Newly Diagnosed Case of HIV Infection: An Experience from a Tertiary Care Hospital in India

Introduction: India has a huge burden of HIV/AIDS infection. Tenofovir based rst line therapy is the preferred treatment for newly diagnosed cases with HIV infection. Methodology: The present prospective study was done among newly diagnosed cases of HIV infection. The patients were followed up for a period of 6 months from the day of enrolment. Sociodemographic parameters, CD4 counts and adverse drug reactions were analysed at baseline and after 6 months. Bi-variate and multi-variate logistic regression was performed with the outcome variable as occurrence of adverse drug reactions. Result: In this study, 67 patients were enrolled with mean age 32.75 (± 14.39) years. Mean CD4 count at start of treatment was 241.5/mm3. Mean difference in CD4 count was 383.05/mm3 (SD = 274.9). Dizziness, tingling, numbness of extremities and muscle cramps were most common adverse effects. On multi-variate logistic regression, occurrence of ADRs was seen to be signicantly higher only in illiterate patients. Conclusion: The present study highlights the importance of long-term follow-up of the patients on antiretroviral therapy. Adequate monitoring of the treatment parameters is of utmost importance.

reactions in patients newly receiving TLE regimen in a tertiary care hospital at Allahabad, Uttar Pradesh and also to study the association between selected variables and occurrence of adverse drug reactions.

Materials And Methods:
The present study was conducted in an ART Centre associated with Moti Lal Nehru Medical College, Allahabad. All patients who were registered in the ART centre over three months of study duration, started on TLE regimen, who were willing to participate and gave written informed consent were included in the study. Participants who were seriously ill, suffering from psychiatric disorders and who could not comprehend interview questions were excluded from the study. A written informed consent was taken from the patient and an attendant in a local language (Hindi). Assent was taken from parents/caregivers in participants who were below 18 years of age.
The prospective cohort of patients was given Tenofovir based rst line therapy with Tenofovir (300 mg), Lamivudine (200 mg) and Efavirenz (600 mg) (TLE) one tablet, once daily as a standard regimen approved by WHO and implemented by the National AIDS Control Organisation (NACO). The patients were observed for a period of six months from the date of enrolment and followed up on monthly basis.
The drugs were dispensed free of cost from the ART Centre of the institute. CD4 count was done as per standard guidelines. The patients with concomitant comorbidities continued to take their treatment.
Sociodemographic pro le, associated comorbidities, baseline CD4 counts were documented in a pretested semi structured questionnaire. Patients were counselled by designated persons regarding the disease process, treatment and adverse events associated with therapy in the ART centre.
The patient registration card issued by the hospital as per NACO guidelines was thoroughly checked for CD4 counts, changes in regimen and any adverse reactions. Each study participant was then given a card containing a unique identi cation code, date of follow up visit and the investigator's contact number to contact if there is any emergency during or after the study period. All norms of con dentiality were strictly maintained and followed. During the follow up period, in every patient with suspected adverse event, a detailed drug history including drugs used during the 3 weeks preceding the adverse reaction, route of administration, dosage, concomitant medical products if any including self-medication and herbal remedies, duration of treatment, improvement after discontinuation of drug, purpose of taking the drug, whether prescribed or over-the-counter drug were noted. A detailed drug reaction history was noted.
Grading of the ADRs was done according to standard guidelines of WHO. The WHO-ADR probability scale and Naranjo's algorithm were used for causality assessment of the ADRs. Severity of the ADR was assessed by Modi ed Hartwig and Siegel Scale. Preventability of ADR was assessed by Modi ed Shummock and Thornton Scale.
In this study, Adverse Drug Reaction is de ned as any response to a drug which is noxious and unintended, and which occurs at doses normally used in man. Poor adherence was de ned as the patient missing one pill in the preceding week.
Data was collected and analysed in STATA version 14.0. Normality test was carried out on all continuous variables and presented as either mean ± standard deviation. Bi-variate logistic regression was done to assess the occurrence of adverse drug reactions with selected variables using chi square test. Variables which were found to be signi cant (at p < 0.25) were considered for inclusion in multi-variate analysis. Multi-variate logistic regression was performed with the outcome variable as occurrence of ADR (coded as binary). Variables with p < 0.05 on multi-variate logistic regression were considered signi cant. The study was approved by institute ethics committee.

Results:
About 70 patients were started on TLE regimen during the study period. Three patients refused to participate and 67 were included in the study.
The age of the patients showed a wide variation ranging from 3 to 65 years. Majority of the patients were females (53.7%), illiterate (41.8%), married (73.1%) and were unemployed or students by occupation (44.7%). Mean monthly income of the patients was 2,321 rupees. It was seen that majority of the patients belonged to nuclear family (85%) with no history of migration (86.6%). (Table-1 The mean CD4 count of the patients was low at the start of treatment (241.5). (Table-1) The mean difference in the CD4 count from the start and 6 months of treatment was available for 51 patients. CD4 values deteriorated in 21 patients (range from − 8 to -407) and improved in 30 patients.
Most common ADR of gastro-intestinal system was anorexia (n = 11) followed by increased appetite (n = 9), atulence (n = 7), diarrhoea (n = 4) and gastritis (n = 4). Most common ADR of skin was maculopapular skin rashes (8) followed by itching (5). Neutropenia (n = 7) was the common laboratory abnormality seen in patients. (Table-3  Bi-variate logistic regression was done to assess the occurrence of ADRs with selected variables. It was seen that occurrence of ADRs was more in males, illiterate patients and those who were currently not working. However, on multi-variate logistic regression, occurrence of ADRs was seen to be signi cantly higher only in illiterate patients. (Table-4 Table 4 Association of ADRs with select socio-demographic variables Discussion: The present study evaluated the occurrence of adverse drug reactions to Tenofovir based rst line ART regimen amongst patients attending tertiary care hospital in Allahabad. In the present study, 53% were females. In a study by Chowta N M et al, it was observed that 53.8% were females amongst patients on Tenofovir regimen, similar to our study. In the present study, it was seen that there was a wide range of delay in start of treatment (mean days of 143.2 (± 493.05) with range from 0 to 2900 days). Majority of the patients were illiterate and were either students/unemployed with a meagre income. These factors might have affected treatment seeking behaviour. However, factors leading to the treatment delay in PLHIV should be assessed in greater detail from patient's and health system's perspective. Necessary remedial measures should be implemented to ensure early treatment initiation.
The mean CD4 counts of the patients at the start of ART was 241.5 cells/mm 3  To the best of our knowledge, the current prospective study is the rst of its kind in Uttar Pradesh exclusively assessing the ADRs due to rst line ART regimen in PLHIV.

Conclusion:
HIV/AIDS, a disease of global concern is widely prevalent. PLHIV have to take ART throughout their life to overcome the effects of HIV/AIDS. Hence, analysing adverse drug reactions to ART regimens, rst line regimens in particular forms a mainstay of treatment course. Multitude of factors play a role in enhancing effective management in PLHIV. Addressing ADRs at the earliest, with necessary treatment modi cations and timely counselling would markedly improve adherence to treatment and ensure better quality of life among PLHIV.