Abacavir-based Regimen for HIV-infected Children and Adolescents

research letter

Indian Pediatr 2019;56: 685-686

Abacavir-based Regimen for HIV-infected Children and Adolescents

Prince Pareek, DK Singh*, Ruchi Rai, Anubha Srivastava and Manisha Maurya

From Department of Pediatrics, MLN Medical College, Allahabad, Uttar Pradesh, India.
Email: [email protected]

We studied 48 children receiving abacavir-based HAART regimen, over a period of one-year for side effects and failure rates. None of the children developed hypersensitivity reaction. The CD4 count significantly improved from the time of enrolment till 12 months of therapy while the failure rate was 14.5%.

Key words: Anti-retroviral drugs, Abacavir; Failure rate; Hypersensitivity reaction.

Abacavir, a nucleoside reverse transcriptase inhibitor (NRTI), is widely used as a combination therapy for treatment of HIV infection in children and adolescents. It is recommended by the World Health Organization (WHO) and National AIDS Control Organization of India (NACO) [1,2]. But, there have been concerns regarding its efficacy and safety [3,4]. Abacavir has been shown to be associated with hypersensitivity reaction, which may prove fatal if the drug is not discontinued [5]. While abacavir is being widely used in children and adolescents who are receiving antiretroviral therapy in India as a part of NACO guidelines, there is paucity of data regarding its side effects and efficacy under pragmatic conditions.

This observational cohort study was conducted at the antiretroviral treatment (ART) center of a tertiary-care teaching hospital over a period of 12 months (from April 2015 to March 2016). All HIV- infected children (18 mo – 18 y) attending the anti-retroviral treatment (ART) center and receiving abacavir-based highly active antiretroviral therapy (HAART) as per NACO guidelines were included. The study was given ethical clearance from the institutional ethics committee and informed consent was taken from parents/grandparents of all the participants

Anthropometry, WHO clinical staging and immunological staging was done at the time of enrolment along with a detailed history and thorough examination. The children were subsequently followed-up every two months for the next one year. At each visit, the children were evaluated for compliance and any side effects of abacavir. Hypersensitivity reaction due to abacavir was defined as presence of two or more of the following symptoms: fever, skin rash, constitutional symptoms (malaise, fatigue, aches), gastrointestinal symptoms (like abdominal pain, nausea, vomiting, diarrhea), respiratory complaints (cough, pharyngitis, dyspnea). A complete blood count, liver function test, renal function test and CD4 counts were done at enrolment and were repeated at 6 months, 12 months, and as and when required. Immunological/clinical failure was defined as per standard NACO guidelines [2].

Fifty children (36 boys) were enrolled in the study. One child died during the study (unrelated to abacavir hypersensitivity) and one child was lost to follow-up. Out of 48 children available for analysis, the mean (SD) age at enrolment was 9.8 (3.4) years. Two-thirds (32) children received combination of Abacavir, Lamivudine and Nevirapine, whereas one-thirds (16) received Abacavir in combination with lamivudine and efavirenz. Hypersensi-tivity was not reported in any participant. Side effects observed included fever (8, 16 %), skin rash (7, 14%), respiratory symptoms (6, 12%), gastrointestinal symptoms (2, 4%), and constitutional symptoms (1, 2%). The mean (SD) CD4 count gradually improved from 648 (463) per mm3 at enrolment to 790 (381) per mm3 after one year of therapy (P=0.006). Immunological failure was seen in 7 (14.5%) children at the end of the study period (Table I).

TABLE I	CD4 Count and Clinical Staging at Enrolment, and After Abacavir-based Therapy

	At enrolment	6 mo	12 mo
*CD4 count (/mm³), mean (SD)	648 (463)	768 (383)	790 (381)
WHO immunological staging, n (%)
Stage 1	22 (45.8)	31 (64.6)	30 (62.5)
Stage 2	18 (37.5)	15 (37.3)	14 (29.2)
Stage 3	8 (16.6)	2 (4.2)	4 (8.3)
*P=0.006 between enrolment and follow-up.

Cruciani, et al. [6] in their systematic review and meta-analysis of randomized controlled trials, compared the virologic efficacy of abacavir/lamivudine with tenofovir/emtricitabine, and found no difference in proportion of subjects with a viral load of <50 copies/mL at 48 weeks and 96 weeks in both the groups. Although there have been concerns regarding side effects of abacavir, especially the hypersensitivity reaction, the incidence has been quite low. Jesson, et al. [9] in their systematic review and meta-analysis of adverse events among children and adolescents receiving regimens that contained abacavir in Africa, found a pooled incidence of hypersensitivity reaction to be 2.2% (95% CI 0.4 to 5.2), discontinuation of abacavir to be 10.9% (95% CI 2.1 to 24.3) and adverse events other than hypersensitivity reaction to be 21.5% (95% CI 2.8 to 48.4). But when they analysed only the randomized controlled trials with comparative data, there was no increase in the risk of hypersensitivity reaction [pooled RR 1.08; 95% CI 0.19 to 6.15].

In India, Chakravarty, et al. [8] reported hypersensitivity in 7.9% children receiving abacavir-based therapy. Out of 8 children who developed hypersensitivity to Abacavir, 2 carried the HLA-B*5701 allele.

We conclude that Abacavir-based regimen appears to be effective in HIV- infected children and adolescents, with no major side effects.

Contributors: PP, DKS: designing the study, analysis of data and writing the manuscript; RR, AS: data collection and critical evaluation of the manuscript; MM: collection of data, analysis and writing of the manuscript.

Funding: None; Competing interest: None stated.

References

1. World Health Organization. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treatment and Preventing HIV Infection. Recommendations for a Public Health Approach. 2nd edition 2016. WHO. Available from: http://www.who.int/hiv/pub/arv/arv-2016/en. Accessed September 27, 2018.

2. National AIDS Control Organization Guidelines 2013. Ministry of Health and Family Welfare, Government of India. Available from: www.naco.gov.in/sites/default/files/Pediatric. Accessed September 25, 2015.

3. Clay PG. The Abacavir hypersensitivity reaction: a review. Clin Ther. 2002; 24:1502-14.

4. Technau KG, Lazarus E, Kuhn L, Abrams EJ, Sorour G, Strehlau R, et al. Poor early virologic performance and durability of abacavir-based first-line regimens for HIV-infected children. Pediatr Infect Dis J. 2013; 32:851-5.

5. Johnson VA. Abacavir. In: Eds Dolin R, Masur H, Saag M, editors. AIDS Therapy. 3rd ed. Philadelphia: Churchil Livingstone, Elsevier 2008; p. 207-24.

6. Cruciani M, Mengoli C, Malena M, Serpelloni G, Parisi SG, Moyle G, et al. Virological efficacy of abacavir: systematic review and meta-analysis. J Antimicrob Chemother. 2014; 69:3169-80.

7. Jesson J, Dahourou DL, Renaud F, Penazzato M, Leroy V. Adverse events associated with abacavir use in HIV-infected children and adolescents: a systematic review and meta-analysis. Lancet HIV. 2016;3:e64-75.

8. Chakravarty J, Sharma S, Johri A, Chourasia A, Sundar S. Clinical abacavir hypersensitivity reaction among children in India. Indian J Pediatr. 2016; 83:855-8.