Acquired Immunodeficiency Syndrome (AIDS) is one of the most destructive epidemics the world has ever witnessed [1]. HIV infection has been and remains as an important cause for morbidity and mortality throughout the world [2].

The incidence of Adverse Drug Reactions (ADRs) among patients on anti-retroviral from both developing and developed countries ranges between 11 and 35.9% [9,10] with incidence being as high as 54% [3] coexistent with opportunistic infection. Most of the ADRs are preventable Unfortunately, up to 25% of patients discontinue their initial HAART regimen because of treatment failure (inability to suppress HIV viral replication to below the current limit of detection, 50 copies/mL), toxic effects or noncompliance within the first 8 months of therapy [4,5].

Many studies have been conducted in Western and African population to study the adverse effect profile to ART, but such studies are scanty in the Indian population. In addition, results from different studies have raised more questions, paving the way for further research in HIV therapeutics in order to optimize treatment with the available resources.

There is a growing need to evaluate adverse effects of ART on patients, so it is important to document adverse effects of antiretroviral therapy for early diagnosis, proper management and prevention in future and hence this was planned to study the toxicity profile towards the commonly used first-line antiretroviral drugs (ART).

Aims and Objectives

To evaluate the thyroid dysfunctions in HIV patients, in a tertiary health care centre, Indira Gandhi Medical College Shimla.

In the prospective study from 1st July 2019 to 30th June 2020, 103 patients registered at ART center Indira Gandhi Medical College hospital were taken up for study.

Inclusion Criteria:

• Patients on ART drugs registered to ART centre IGMC SHIMLA

• Patients aged > 18 years

• Those that consent to participate in the study

Exclusion Criteria:

• Age<18y

• Pregnancy

• Baseline deranged renal function test, Liver function test, pre-existing anaemia

• Concomitant Hepatitis B, C & Tuberculosis patients

• On drugs likely to cause Renal or Hepatic impairment

• Patient of Alcohol abuse

• Patient not compliant to ART treatment

• Patient admitted in ward.

• Patients not willing to give consent

Method of Data Collection

All consecutive patients presenting in the ART center of IGMC Shimla were recruited after proper counselling and written informed consent. 

A detailed history with duration of symptoms was taken and recorded as per the case recording format. All patients were subjected to detailed clinical examination and relevant laboratory investigations as per Performa. Data was collected from patient case sheet during follow up at 6 months and also by interviewing the patient directly. Patients were asked to visit the ART Centre if they developed any symptoms or on follow up at 6 months.

Statistical Analysis 

The data was entered in Microsoft excel sheet and was analysed using Epi-info software. Descriptive statistical analysis has been carried out in the present study. Results on continuous measurements are presented on Mean ± SD (Min-Max) and results on categorical measurements are presented in Number (%). Chi-square and fisher exact test were used to find the significance of drug induced liver damage for various risk factors. Significance is assessed at 5% level of significance.

This study was conducted in department of medicine in Indira Gandhi Medical College Shimla, H.P. There were a total of 103 patients who were enrolled in the study after obtaining consent form from patients and ethical approval from institutional ethical committee.

There were a total of 103 patients, out of which there were 56 (54.4%) males and 47 (45.6%) females with male to female ratio of 1.19:1. Age group of 18-35 years was the most affected with 45 (43.7%) patients followed by 36-50 years with 42 (40.8%) patients. Most of the males were in age group of 18-35 years i.e. 30/56 (53.5%), while females were predominantly in age group of 36-50 years with a count of 23/47 (48.9%) females. Mean age of males was (36.91±10.04 years) lower than that of females (40.17±11.14 years) (Table 1).

There were 59 (57.3%) patients with normal BMI followed by 20 (19.4%) patients who were overweight. 19 (18.4%) patients had BMI of less than 17.5 i.e. underweight and 5 (4.9%) were obese. In our study, there were 53 (51.5%) patients from rural area and 50 (48.5%) from urban area (Table 2).

After enrolment the baseline biochemical parameters of patients were recorded. The haemoglobin of patients at baseline was 13.99±0.93 in males and 13.96±0.97 in females which decreased in both groups to 13.62±0.95 in males and 13.15±1.28 in females. TLC count was increased in males from 6.48±1.65 to 6.59±1.61 while in females it decreased from 6.38±1.46 to 5.89±2.09. Urea, Creatinine, Bilirubin, SGOT, SGPT, ALP and triglyceride levels increased in both groups from baseline levels to levels after 6 months of treatment (Table 3).

Table 1: Age and Gender Distribution of Study Participants

Table 2: BMI and Area distribution

Table 3: Laboratory parameters at baseline and at 6th month:

About 15 patients, 5 males and 10 females reported nausea after treatment while gastrointestinal intolerance was reported by a total of 12 patients with 7 males and 5 females. Rash was reported as ADR by 6 males and 5 females. We observed anemia as a side effect of ART in 8 males and 7 females while leukopenia was observed in 1 male and 8 females. There were 4 cases of renal toxicity with all 4 females. Mixed type and hepatocellular type of liver toxicity was seen in 2 males and 1 female each and transaminitis was observed in 4 males and 2 females (Table 4).

Table 4: Adverse drug reactions and toxicity

Table 5: Various lab parameters

SGOT was raised by more than 2.5 to 5 times upper normal limit in 5 males and 5 females while it was raised more than 5 times in 2 males only. SGPT was observed to be raised by 2.5 to 5 times in 6 males and 5 females and was raised by more than 5 times in only 1 males with no females with SGPT raised more than 5 times. It was less than 1.25 times in 35 males and 28 females. ALP was raised by more than 1.1 to 1.5 times in 4 and 1 male and female respectively while more than 1.6 times raised values were observed in 4 males and 2 females. Jaundice with bilirubin values more than 2.5 times upper normal limit was seen in 3 males and 1 female and values less than 1 were observed in 44 males and 34 females (Table 5).

This study was conducted in a tertiary care hospital IGMC, Shimla, Himachal Pradesh on adult patients on ART. There were a total of 103 patients with a total of 131 ADRs. Out of all patients, there were 56 (54.4%) males and 47 (45.6%) females with male to female ratio of 1.19:1. Similarly, Anwikar et al. [6] reported that in their study there were 1844 patients, of these 1198 (65%) were male and 646 (35%) were female. In a study by Reddy et al. [10], there were 208 males and 92 females with male to female ratio of 2.26:1. Gabbita et al. [7] in their study observed that a total of 453 patients were treated by the 1st line antiretroviral TLE regimen of which 211 were male patients, 241 were female patients and 1 transgender patient.

Age group of 18-35 years was the most affected with 45 (43.7%) patients followed by 36-50 years with 42 (40.8%) patients. Most of the males were in age group of 18-35 years i.e. 30/56 (53.5%), while females were predominantly in age group of 36-50 years with a count of 23/47 (48.9%) females. Mean age of males was (36.91±10.04 years) lower than that of females (40.17±11.14 years). Similarly, Patil et al. [9] observed that the most common age group taking ART was less than 35 years with 68 (62.3%) patients and Kumari et al. [8] observed that there were 119/280 (42.5%) patients in age group of 18-30 years. 

In our study we observed a total of 131 ADRs and out of which 61 ADRs were reported in males and 70 in females. Similarly, in a study by Patel et al. [9], females (60.55%) had higher prevalence of ADRs than males (39.45%). Similar results were found in previous study by Patel et al. [50] females were reported to have higher incidence of ADRs (1.80 ADR per patient, 117/65) than males (1.57 ADR per patient, 157/100). But in study by Reddy et al. [10] males had higher prevalence of ADRs as compared to female patients. Possible explanation for this gender difference in ADR incidence could be a gender specific difference in in body mass index, fat composition, drug susceptibility, hormonal effects on drug metabolism and elimination, or genetic constitutional differences on the levels of various enzymes although the same has not been proven conclusively [9,10,11].

In our study, the most common ADRs were haematological ADRs (46; 44.66%). Out of which there were 15 cases of anemia, 9 cases of leukopenia, 7 of thrombocytosis and 10 and 5 cases of microcytosis and macrocytosis respectively. Gabbita et al. [7] reported in their study that the haematological ADRs presented as anemia (31;39.2%) and pancytopenia (1;1.26%). Reddy et al. [10] observed that 15 (9.37%) ADRs were related to haematological system with 8.13% cases with anemia. Kumari et al. [8] observed that blood and lymphatic system associated ADRs included anaemia (52, 22.80%) and pallor (4, 1.75%).

In our study, cutaneous ADRs were rash and itching seen in 11 (10.67%) patients. Gabbita [7] reported cutaneous ADRs as rash in 30 (37.9%). Reddy [10] reported rash in 8.75% and maculopapular rash in 7.5% cases. Kumari et al. [8] reported skin rashes in 18 (7.89%). There were 3 (1.31%) patients who presented with Stevens Johnson Syndrome. 

There were 27 (26.21%) cases of gastrointestinal ADRs in our study with 15 (14.5%) cases of nausea and 12 (11.65%) cases of gastrointestinal intolerance. In study by Reddy et al. [10], there were 38 (23.75%) cases of gastrointestinal ADRs. Kumari et al. [8] observed 11 (4.82%) cases of abdominal pain, 8 (3.5%) cases of vomiting, 5 (2.19%) cases of diarrhoea and 5 (2.19%) cases of anorexia. There were 3 (1.31%) cases of gastric intolerance in their study. Reddy et al. [10] observed 13.13% cases of gastritis and 6.87% cases of anorexia.

We observed a total of 12 (11.65%) cases of hepatitis out of which there were 3 cases each of mixed and hepatocellular liver toxicity and 6 cases of transaminitis. Reddy et al. [10] observed 2 (1.25%) cases of liver ADR while Kumari et al. [8] observed 12 (5.26%) cases with raised liver enzymes.

In our study there were 5 (4.85%) cases who reported with nephrotoxicity similarly Gabbita et al. [7] reported 6 (7.59%) cases with renal failure and 2 (2.53%) cases with acute kidney injury. Nephrotoxicity was observed in 1 (1.26%) case. 

CNS symptoms like headache or insomnia (7;6.8%) and neuropathy (3;2.91%) were also reported in our study. there were 19 (11.87%) cases of CNS related ADRs in a study by Reddy et al. [10] and Kumari et al. [8] reported insomnia in 24 (10.52%) and headache in 16 (7.01%) patients. Parasthesia was reported by 3.75% of patients in study by Reddy et al. [42] while Kumari et al. [8] observed peripheral neuropathy in 4 (1.75%) of cases and tremors in 3 (1.31%) cases. Rukmangathen et al. [12] observed that nervous system related disorders were the most commonly observed ADRs in patients receiving TLE regimen which includes drowsiness/giddiness (53.62%) followed by headache (15. 94%) and nightmares (8.69%).

We observed that 7 (6.8%) patients had fatigue, 5 (4.85%) had lipoatrophy and 1 had pancreatitis as an ADR to ATT. Anwikar et al. [6] observed lipodystrophy in 0.38% cases. Rukmangathen et al. [12] observed lipoatrophy in 20 (8.69%) cases and Reddy AK observed lipodystrophy and pancreatitis each in 2 (0.66%) cases.

With the increasing access to use of HAART it is possible that there is an increased risk of drug induced illness due to HAART. Early detection and management of ADRs will reduce the economic burden and improve the medication adherence resulting in better therapeutic outcomes.

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