Efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV infected children and adolescents: a systematic review and meta-analysis.
BACKGROUND
Abacavir is one of the recommended nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infections among children and adolescents. However, there are concerns that the antiviral efficacy of abacavir might be low when compared to other NRTIs especially among children. There are also concerns that abacavir use may lead to serious adverse events such as hypersensitivity reactions and has potential predisposition to developing cardiovascular diseases


METHODS
We searched four electronic databases, four conference proceedings and two clinical trial registries in August 2014, without language restrictions. Experimental and observational studies with control groups that examined the efficacy and safety of abacavir-containing regimens in comparison with other NRTIs as first-line treatment for HIV-infected children and adolescents aged between one month and eighteen years were eligible. Two authors independently screened search results, extracted data and assessed the risk of bias of included studies using a pre-specified, standardised data extraction form and validated risk of bias tools. We also assessed the quality of evidence per outcome with the GRADE tool.


RESULTS
We included two randomised controlled trials (RCTs) and two analytical cohort studies with a total of 10,595 participants. Among the RCTs we detected no difference in virologic suppression after a mean duration of 48 weeks between abacavir- and stavudine-containing regimens (2 trials; n = 326: RR 1.28; 95 % CI 0.67-2.42) with significant heterogeneity (P = 0.02; I(2) = 81 %). We also found no significant differences between the two groups for adverse events and death. After five years of follow-up, virologic suppression improved with abacavir (1 trial; n = 69: RR 1.96; 95 % CI 1.11-3.44). For cohort studies, we detected that the virologic suppression activity of abacavir was less effective than stavudine in both the lopinavir/ritonavir (1 study, n = 2165: RR 0.79, 95 % CI 0.67-0.92) and efavirenz sub-groups (1 study, n = 3204: RR 0.79, 95 % CI 0.67-0.92) respectively. The quality of evidence from RCTs was moderate for virologic suppression but low for death and adverse events, while that of cohort studies was low for all three these outcomes.


CONCLUSIONS
Available evidence showed little or no difference between abacavir-containing regimen and other NRTIs regarding efficacy and safety when given to children and adolescents as a first-line antiretroviral therapy.
Centre for Evidence-based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7505, South Africa. olatunji@sun.ac.za.|Division of Community Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7505, South Africa. olatunji@sun.ac.za.
Olatunji O
OO
Adetokunboh
Centre for Evidence-based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7505, South Africa. anelschoonees@sun.ac.za.
Anel
A
Schoonees
Division of Community Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7505, South Africa. tolulopeb@sun.ac.za.
Tolulope A
TA
Balogun
Centre for Evidence-based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7505, South Africa. charlesw@sun.ac.za.|Division of Community Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7505, South Africa. charlesw@sun.ac.za.
Charles S
CS
Wiysonge
D000293:Adolescent; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D048588:Benzoxazines / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D061466:Lopinavir / Q000627:therapeutic use; D008297:Male; D019438:Ritonavir / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use; D000099227:Abacavir
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D061466:Lopinavir; D019438:Ritonavir; D018119:Stavudine; D000099227:Abacavir; C098320:efavirenz