Reuse of nevirapine in exposed HIV-infected children after protease inhibitor-based viral suppression: a randomized controlled trial.
BACKGROUND
Protease inhibitor (PI)-based therapy is recommended for infants infected with human immunodeficiency virus (HIV) who were exposed to nevirapine for prevention of mother-to-child HIV transmission. However, there are limitations of continuing PI-based therapy indefinitely and reuse of nevirapine has many advantages.


OBJECTIVE
To test whether nevirapine-exposed infants who initially achieve viral suppression with PI-based therapy can maintain viral suppression when switched to nevirapine-based therapy.


METHODS
Randomized trial conducted between April 2005 and May 2009 at a hospital in Johannesburg, South Africa, among 195 children who achieved viral suppression less than 400 copies/mL for 3 or more months from a cohort of 323 nevirapine-exposed children who initiated PI-based therapy before 24 months of age.


METHODS
Control group children continued to receive ritonavir-boosted lopinavir, stavudine, and lamivudine (n = 99). Switch group children substituted nevirapine for ritonavir-boosted lopinavir (n = 96).


METHODS
Children were followed up for 52 weeks after randomization. Plasma HIV-1 RNA of greater than 50 copies/mL was the primary end point. Confirmed viremia greater than 1000 copies/mL was used as a criterion to consider regimen changes for children in either group (safety end point).


RESULTS
Plasma viremia greater than 50 copies/mL occurred less frequently in the switch group (Kaplan-Meier probability, 0.438; 95% CI, 0.334-0.537) than in the control group (0.576; 95% CI, 0.470-0.668) (P = .02). Confirmed viremia greater than 1000 copies/mL occurred more frequently in the switch group (0.201; 95% CI, 0.125-0.289) than in the control group (0.022; 95% CI, 0.004-0.069) (P < .001). CD4 cell response was better in the switch group (median CD4 percentage at 52 weeks, 34.7) vs the control group (CD4 percentage, 31.3) (P = .004). Older age (relative hazard [RH], 1.71; 95% CI, 1.08-2.72) was associated with viremia greater than 50 copies/mL in the control group. Inadequate adherence (RH, 4.14; 95% CI, 1.18-14.57) and drug resistance (RH, 4.04; 95% CI, 1.40-11.65) before treatment were associated with confirmed viremia greater than 1000 copies/mL in the switch group.


CONCLUSIONS
Among HIV-infected children previously exposed to nevirapine, switching to nevirapine-based therapy after achieving viral suppression with a ritonavir-boosted lopinavir regimen resulted in lower rates of viremia greater than 50 copies/mL than maintaining the primary ritonavir-boosted lopinavir regimen.


BACKGROUND
clinicaltrials.gov Identifier: NCT00117728.
Coovadia
Ashraf
A
Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa.
Abrams
Elaine J
EJ
Stehlau
Renate
R
Meyers
Tammy
T
Martens
Leigh
L
Sherman
Gayle
G
Hunt
Gillian
G
Hu
Chih-Chi
CC
Tsai
Wei-Yann
WY
Morris
Lynn
L
Kuhn
Louise
L
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D019259:Lamivudine / Q000627:therapeutic use; D061466:Lopinavir; D008297:Male; D018811:Maternal Exposure; D019829:Nevirapine / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D018119:Stavudine / Q000627:therapeutic use; D016896:Treatment Outcome; D014766:Viremia
D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine
Clin Infect Dis. 2006 Oct 1;43(7):939-41
16941380
J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):566-9
18197120
Antivir Ther. 2007;12(4):453-8
17668553
Antivir Ther. 2008;13 Suppl 2:101-7
18575198
HIV Med. 2008 Oct;9(9):747-56
18651856
Pediatrics. 2003 Mar;111(3):e275-81
12612284
Int J Epidemiol. 2007 Oct;36(5):1009-21
17533166
Pediatrics. 2007 Jun;119(6):e1371-83
17533177
Clin Infect Dis. 2002 Feb 15;34(4):504-10
11797178
JAMA. 2008 Aug 6;300(5):555-70
18677028
AIDS. 2009 Jun 1;23(9):1097-107
19417581
J Acquir Immune Defic Syndr. 2007 Feb 1;44(2):148-53
17117145
N Engl J Med. 2008 Nov 20;359(21):2233-44
19020325
AIDS. 2003 Jun 13;17(9):1319-27
12799553
J Antimicrob Chemother. 2006 Aug;58(2):235-42
16807250
BMC Pediatr. 2008 Sep 04;8:34
18771599
AIDS. 2007 May 11;21(8):957-64
17457089
J Infect Dis. 2010 Apr 15;201(8):1121-31
20214476
J Acquir Immune Defic Syndr. 2005 Apr 1;38(4):480-7
15764965
Clin Infect Dis. 2009 Feb 15;48(4):462-72
19133804
J Acquir Immune Defic Syndr. 2001 Jul 1;27(3):229-36
11464141
N Engl J Med. 2003 Sep 11;349(11):1036-46
12968087
J Acquir Immune Defic Syndr. 2009 Sep 1;52(1):132-6
19506483
HIV Med. 2002 Apr;3(2):146-55
12010362
AIDS. 2004 Sep 3;18(13):1753-68
15316336
AIDS. 2003 Nov 21;17(17):2451-9
14600516
N Engl J Med. 2007 Jan 11;356(2):135-47
17215531
BMC Infect Dis. 2008 Oct 22;8:144
18945352
Clin Infect Dis. 2000 Nov;31(5):1274-8
11073763