APIK Journal of Internal Medicine

: 2022  |  Volume : 10  |  Issue : 1  |  Page : 34--38

A clinical profile of adverse drug reaction in HIV patients on highly active antiretroviral therapy

Nitish Ashok Gurav, K Ravi, B Sumana, Avinash Hannabe Rajanna, Rakesh Shetty Rajalbandi 
 Department of Internal Medicine, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India

Correspondence Address:
Dr. Avinash Hannabe Rajanna
006, White Rose, MSV Vivek Marvel Apartment, Yelahanka, Bengaluru - 560 064, Karnataka


Background: The expansion of antiretroviral therapy has increased the life expectancy of patients living with HIV (PLHIV). However, the Highly Active Antiretroviral Therapy (HAART) has a wide range of toxicity ranging from low grade intolerance to life threatening adverse drug reactions (ADR). Mild toxicity does not require any change in therapy. Moderate to severe toxicity may require substitution with an alternate class of drug while life threatening side effects need discontinuation of HAART till the condition of patient is stabilized and toxicity is resolved. Aim and Objective: To estimating the frequency of occurrence of ADRs in PLHIV on HAART. To estimate the clinical profile and severity of ADRs. Materials and Methods: The data of the patient who were registered at Centre of Excellence, Bowring and Lady Curzon Hospital, Bangalore Medical Collage & Research Institution, Bangalore, from May 2015 to April 2017, were retrospectively reviewed. Demographic data, routine blood investigations, ADRs and CD4 count at that time were noted. Results: In our study conducted from May 2015 to April 2017, 1834 PLHIV were included. Out of these patients, 1554 PLHIV were on HAART. 601 patients showed ADRs secondary to HAART. The age distribution was between 18 to 75 years and the mean age was 43.19+9.18. M: F:: 62:38. 409 patients had hypertriglyceridemia, 472 patients had hypercholesterolemia, 84 had hyperbilirubinemia, 48 developed anemia, 17 patients developed hepatotoxicity, 25 developed drug induced skin rash. Significant association was found between the above reactions and the causative drug. Other reactions like hyperglycemia, night mares, Steven Johnson syndrome (SJS) observed in the study did not show statistical significance. Conclusion: The commonly observed adverse drug reactions of HAART were hypertriglyceridemia, hypercholesterolemia, hyperbilirubinemia, anemia, hepatotoxicity and skin rashes. However hyperglycemia, SJS, night mares were rarely seen.

How to cite this article:
Gurav NA, Ravi K, Sumana B, Rajanna AH, Rajalbandi RS. A clinical profile of adverse drug reaction in HIV patients on highly active antiretroviral therapy.APIK J Int Med 2022;10:34-38

How to cite this URL:
Gurav NA, Ravi K, Sumana B, Rajanna AH, Rajalbandi RS. A clinical profile of adverse drug reaction in HIV patients on highly active antiretroviral therapy. APIK J Int Med [serial online] 2022 [cited 2022 Sep 28 ];10:34-38
Available from: https://www.ajim.in/text.asp?2022/10/1/34/335080

Full Text


Standard antiretroviral therapy (ART) consists of the combination of antiretroviral (ARV) drugs to maximally suppress the HIV and stop the progression of HIV disease. As per the WHO 2018 statistics, in the year 2017, only 59% of adults and 52% of children living with HIV were receiving lifelong ART. Between 2000 and 2017, the total number of new HIV infections came down by 36% and HIV-related deaths by 38% due to ART.[1] The WHO recommends ART for all people with HIV as soon as possible after diagnosis without any restrictions of CD4 counts. Countries are now following to adapt and implement these recommendations within own epidemiological settings.[2] India has the second-largest HIV treatment program in the world. The WHO announced a global policy to treat all people with HIV in September 2015, with the full guidelines published in 2016. The expanded use of ART is supported by recent findings from clinical trials confirming that early use of ART keeps people living with HIV alive and healthier and reduces the risk of transmitting the virus to partners.[3]

The National AIDS Control Programme (NACP) is a centrally sponsored scheme through the State AIDS Control Programme for prevention and control of HIV/AIDS. NACP IV (2012–2017) had two main objectives – to reduce new infections by 50% (with respect to 2007 baseline under NACP III) and provide comprehensive care and support to all patients living with HIV (PLHIV) and treatment service to all those who require it.

Despite the known benefits of highly active ART (HAART), adverse drug reactions (ADRs) due to HAART limit the usage of HAART in PLHIV. Health-care professionals who attend to HIV infected must have adequate knowledge about various ADRs and safety profile of HAART, as the ADRs can be treated accordingly.

Aim and objective

To estimating the frequency of occurrence of ADRs in PLHIV on HAARTTo describe the clinical profile of ADRs.

 Materials and Methods

Permission to perform the study was obtained from Karnataka State AIDS Prevention Society and institutional ethics committee clearance was obtained. A total of 1834 PLHIV who were on HAART were evaluated for ADRs. The study period was from May 2015 to April 2017 conducted at Centre of Excellence, Bowring and Lady Curzon Hospital, Bangalore Medical College and Research Institution, Bangalore. Information of the patients and clinical data is collected using preformed pro forma at the time of follow-up. Steps were taken to send for all the investigations and detailed clinical examination of the patient was done. Patients included were PLHIV patients on HAART with presence of one or more ADRs presumed to be caused by HAART. HIV patients with adverse reaction/side effects due to causes other than HAART were excluded from the study.

The demographic history, relevant medical history, and clinical and laboratory data (with baseline normal characters) of the patients and ADRs were noted and compiled as per the “The WHO-UMC system for standardized causality assessment.” Data were analyzed by descriptive statistics; Chi-square test was used for association of categorical variables. Pearson coefficient of correlation was used for correlation of quantitative variables.


In our study performed on a total of 1834 PLHIV, 601 patients showed adverse drug reactions.


In our study 62.1% Male and 37.9% Female [Figure 1] and [Table 1]. Maximum age group of study 41-50 years (41.9%), Followed by 31-40 (31.4%) [Table 2] and [Figure 2].{Figure 1}{Table 1}{Table 2}{Figure 2}

The following were the results obtained.

In our study most patients had BMI of 18.5-22.9(40.8%), Followed by 25-29.9(24.3%) and Then BMI 23-24.9(21.6%) respectively. [Table 3] and [Figure 3]{Table 3}{Figure 3}

In this study, mean age was 43.19+9.18, mean BMI of 23.16+3.77 and mean CD4 count 510 +269 respectively [Table 4].{Table 4}

In our study major adverse drug reactions are, 37.08% had hypercholestremia, 32.1% had hyper triglyceridemia, 6.6% hyperbilirubenemia, and 3.77% anemia [Table 5] and [Figure 4].{Figure 4}{Table 5}


The common mild ADR due to HAART were gastrointestinal disturbances such as bloating, nausea, fatigue, headache, and diarrhea, which may be transient or persist throughout the therapy period. However, the above-noted ADRs warrant more detailed discussion. All patients showing ADRs were closely monitored and the following measures were taken to treat the consequences.

Shenoy et al. studied 327 PLHIV, of which 43 patients developed ADRs. Anemia, hepatitis, and dermatological adverse effects are the most common and antitubercular therapy was the common cause of ADRs. Zidovudine-induced anemia was seen in 15% of patients.[4] A study on tribal population PLHIV in Chhattisgarh showed peripheral neuropathy and skin rashes as common ADRs.[5]

In our study patients on ZLN, major ADRs were 260 have developed hypertriglyceridemia, 251 hypercholesterolemia, 42 anemia, 15 neurotoxicity, and 10 hepatotoxicity. Patients on TLE 122 have developed hypertriglyceridemia, 121 hypercholesterolemia, 6 anemia, 13 neurotoxicity, and 8 hepatotoxicity. In patients on TDF + 3TC + ATV/RTV, 25 have developed Hypertriglyceridemia, 78 hypercholesterolemia, and 79 hyperbilirubinemia. In patients on RAL + DRV + RTV, 2 have developed Hypertriglyceridemia, 3 hypercholesterolemia, and 1 hyperbilirubinemia [Table 6].{Table 6}

Zidovudine-related anemia usually occurs within 3 months after therapy initiation. Risk factors include high zidovudine dosage, increased treatment duration, low CD4 cell count, and preexisting anemia.[6] In majority of patients, anemia developed within 6 months of start of therapy. Females were found to be more prone to develop anemia. Zidovudine has been known to cause a severe hypoproliferative anemia that is dose related. Patients who have developed toxicity should not have their dose reduced to improve tolerability but should the drug replaced by another. Some patients, however, may come to medical attention after having stopped taking the drug for 1–2 weeks and may already be in the recovery phase and present with severe anemia, normoblastemia, and reticulocytosis.[7] Granulocyte colony-stimulating factor has been shown in a number of studies to resolve neutropenia caused by zidovudine.[8] Similarly, erythropoietin is effective in treating anemia associated with HIV.

Patients infected with HIV had higher incidence of drug-induced skin manifestations mainly due to nevirapine-based regimen. It ranges from mild rash to Steven–Johnson syndrome (SJS) and toxic epidermal necrolysis. Rashes were accompanied with fever and mucositis which subsides after stopping the drug.[9],[10] The National Treatment Guidelines recommend that HIV patients to be started on low-dose nevirapine in the 1st 2 weeks to minimize its adverse effects before a full dose is given.[11] Kumaraswamy et al. studied reasons for modification and discontinuation of HAART in south Indian patients. The most common reason for modifying therapy was the development of an ADR in 64% of patients, followed by the cost of therapy in 19% of patients and treatment failure in 14% of cases. Skin rash, hepatotoxicity, and anemia were common ADRs noted.[12]

To conclude, dyslipidemia, hyperbilirubinemia, anemia, hepatotoxicity, and skin rashes were common ADRs [Table 7]. Hepatotoxicity was mainly due to antitubercular therapy. Life-threatening ADRs such as pancreatitis and SJS require inpatient care. Health-care professionals who attend to HIV-infected must have adequate knowledge about various ADRs and safety profile of HAART. Multicentric studies involving large sample size and meta-analysis are required to provide more valuable data on safety profile and pattern of ADRs in PLHIV.{Table 7}


Out of the total sample number of ADRs, hypertriglyceridemia, hypercholesterolemia, unconjugated hyperbilirubinemia, anemia, hepatotoxicity, neurotoxicity, and skin rashes were statistically significant. Neurotoxicity was seen mainly due to usage of non-ART drugs in PLHIV like antitubercular therapy-induced neuropathy. Deranged renal function, pancreatitis, lipodystrophy, hyperglycemia, SJS, and nightmares were other ADRs which were not statistically significant. Dyslipidemia was seen mainly in ZLN and TLE regime patients. Unconjugated hyperbilirubinemia was seen in atazanavir-based regime. Anemia is prevalent in zidovudine-based regime and skin rashes due to efavirenz-based regime. Although it was not statistically significant, pancreatitis and deranged renal functions seen in patients on tenofovir-based regime could be life-threatening and mandated discontinuation of tenofovir and usage of an alternate regime.

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Conflicts of interest

There are no conflicts of interest.


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