Newer treatments for HIV in children

Current Opinion in Pediatrics

Volumn 16, Issue 1, 2004, Pages 76-79

  McKinney Jr , Ross E ^a   Cunningham, Coleen K ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Children; Human immunodeficiency virus

Indexed keywords

ABACAVIR; ANTIVIRUS AGENT; DIDANOSINE; EFAVIRENZ; EMTRICITABINE; ENFUVIRTIDE; LAMIVUDINE; NELFINAVIR; NEVIRAPINE; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; STAVUDINE; TENOFOVIR DISOPROXIL; ZIDOVUDINE;

ADULT; AGE DISTRIBUTION; ANAMNESIS; CAPSULE FILLING; CHILD; CHILD CARE; CHILDHOOD DISEASE; CLINICAL TRIAL; DOSE RESPONSE; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG COATING; DRUG EFFECT; DRUG EXPOSURE; DRUG FORMULATION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG MONITORING; DRUG RELEASE; DRUG SENSITIVITY; DRUG TOLERABILITY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IN VITRO STUDY; INJECTION SITE; LABORATORY TEST; MEDICAL INFORMATION; MEDICAL RECORD; MEDICAL RESEARCH; NONHUMAN; PEDIATRICS; PHYSICIAN; POWDER; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SKIN MANIFESTATION; STANDARDIZATION;

ADENINE; ANTI-BACTERIAL AGENTS; ANTI-HIV AGENTS; CHILD; DEOXYCYTIDINE; DIDANOSINE; DRUG THERAPY, COMBINATION; HIV ENVELOPE PROTEIN GP41; HIV FUSION INHIBITORS; HIV INFECTIONS; HUMANS; MICROBIAL SENSITIVITY TESTS; ORGANOPHOSPHORUS COMPOUNDS; PEPTIDE FRAGMENTS; PHOSPHONIC ACIDS; RANDOMIZED CONTROLLED TRIALS; REVERSE TRANSCRIPTASE INHIBITORS; STAVUDINE;

EID: 0842287110     PISSN: 10408703     EISSN: None     Source Type: Journal    
DOI: 10.1097/00008480-200402000-00014     Document Type: Review

References (22)

1. King JR, Kimberlin DW, Aldrovandi GM, et al: Antiretroviral pharmacokinetics in the paediatric population: a review. Clin Pharmacokinet 2002, 41:1115-1133. An excellent review of the complex issue of pediatric antiretroviral pharmacokinetics.
2. Molina J-M, Ferchal F, Rancinan C, et al. Once-daily combination therapy with emtricitabine, didanosine, and efavirenz in human immunodeficiency virus-infected patients. J Infect Dis 2000, 182:599-602
3. Ena J, Pasquau F: Once-a-day highly active antiretroviral therapy: a systematic review. Clin Infect Dis 2003, 36:1186-1190. A small-scale meta-analysis of studies of once-daily antiretroviral regimens in adults. Because most of the studies are still under way, the analysis is preliminary, but it shows promise for these easier-to-take regimens.
4. th Conference on Retroviruses and Opportunistic Infections. (Boston, MA, USA, February 10-14, 2003):376
5. King JR, Nachman S, Yogev R, et al. Single-dose pharmacokinetics of enteric-coated didanosine in HIV-infected children. Antivir Ther 2002, 7:267-270.
6. Von Rompay KK, McChesney MB, Aguirre NL, et al.: Two low doses of tenofovir protect newborn macaques against oral simian immunodeficiency virus infection. J Infect Dis 2001, 184:429-438.
7. Staszewski S, Gallant J, Pozniak A, et al. Efficacy and safety of tenofovir disoproxil fumarate (TDF) versus stavudine (d4T) when used in combination with lamivudine (3TC) and efavirenz (EFV) in HIV-1 infected patients naive to antiretroviral therapy (ART): 48-week interim results (abstract LbOr17). In Program and Abstracts. XIV International AIDS Conference (Barcelona, Spain, July 7-12, 2002).
8. Tarantal AF, Castillo A, Ekert JE, et al: Fetal and maternal outcome after administration of tenofovir to gravid rhesus monkeys (Macaca mulatta). J Acquir Immune Defic Syndr 2002, 29:207-220.
9. Castillo AB, Tarantal AF, Watnik MR, et al.: Tenofovir treatment at 30 mg/kg/day can inhibit cortical bone mineralization in growing rhesus monkeys (Macaca mulatta). J Orthop Res 2002, 20:1185-1189.
10. Church J, Cunningham CK, Hughes M, et al.: Safety and antiretroviral activity of chronic subcutaneous administration of T-20 in HIV-1 infected children. Pediatr Infect Dis J 2002, 21:653-659. The initial phase I study of enfuvirtide in children. The results showed preliminary efficacy and reasonable tolerance, despite the subcutaneous injection route of administration.
11. Geretti AM, Smith M, Watson C, et al.: Primary antiretroviral resistance in newly diagnosed patients with established heterosexually acquired HIV-1. AIDS 2002, 16:2358-2360.
12. Parker M, Wade N, Lloyd RM, et al.: Prevalence of genotypic drug resistance among a cohort of HIV infected newborns. JAIDS 2003, 32:292-297. These authors evaluated a large cohort of HIV-infected newborns from New York State and established a moderate rate of antiretroviral resistance in early samples from 12[ref] of the neonates. These results demonstrate that a significant portion of newly infected neonates have primary infection with resistance virus and therefore may not suppress HIV, even if adherent to the medication regimens.
13. Mullen J, Leech S, O'Shea S, et al. Antiretroviral drug resistance among HIV-1 infected children failing treatment. J Med Virol 2002, 68:299-304.
14. Cohen NJ, Oram R, Elsen C, et al.: Response to changes in antiretroviral therapy after genotyping in human immunodeficiency virus-infected children. Pediatr Infect Dis J 2002, 21:647-653. This study is limited by an extremely small patient sample but raises the important question of whether knowledge of the viral genotype allows the clinical outcome to be improved. In their small cohort, it made no difference.
15. Baxter JD, Mayers DL, Wentworth DN, et al.: A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. CPCRA 046 study team for the Terry Beirn Community Programs for Clinical Research on AIDS. AIDS 2000, 14:F83-F93.
16. Ruff CT, Ray SC, Kwon P, et al.: Persistence of wild-type virus and lack of temporal structure in the latent reservoir for human immunodeficiency virus type-1 in pediatric patients with extensive antiretroviral exposure. J Virol 2002, 76:9481-9492. This is a very well done study that clearly demonstrates the persistence of archived but replication-competent virus after many years of excellent viral suppression. The clear implication is that all previous viral quasi-species are likely archived and are able to grow out whenever drug pressure is removed.
17. Van Heeswijk RPG, Scherpbier HJ, de Koning LA, et al. The pharmacokinetics of nelfinavir in HIV-1 infected children. Ther Drug Monitor 2002;24:487-491, 2002.
18. Treluyer JM, Burgard M, Cazali N: at al. Relationship between antiretroviral drug plasma concentrations and viral load in children [letter]. JAIDS 2003, 32:112-115. Although this report is just a brief letter to the editor, it contains very useful information relating successful viral suppression to blood levels of antiretroviral agents obtained at a single timepoint in children on treatment. The authors suggest that much can be learned from therapeutic drug monitoring; clearly, such approaches need to be evaluated further.
19. King JR, Acosta EP, Chadwick E, et al.: Evaluation of multiple drug therapy in human immunodeficiency virus-infected pediatric patients. Pediatr Infect Dis J 2003, 22:239-244. A retrospective evaluation, which is flawed by a wide variety of regimens, the inclusion of hydroxyurea (which is now generally discredited) in some treatment schemes, and the inability to tell whether patients dropped out before a year had passed or were still on treatment at the time of the analysis. Given the nearly hopeless situation for many of these children, this complex approach was more promising than might have been expected.
20. Krogstad P, Lee S, Johnson G, et al.: Nucleoside-analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir for pretreated children infected with human immunodeficiency virus type 1. Clin Infect Dis 2002, 34:991-1001. An excellent summary of a well-run study that is unfortunately limited in its current applicability because few children are using nucleoside-only regimens, the group included in this investigation.
21. Floren LC, Wizna A, Hayashi S, et al.: Nelfinavir pharmacokinetics in stable human immunodeficiency virus-positive children: Pediatric AIDS Clinical Trials Group Protocol 377. Pediatrics 2003, 112:e220-e227. An important article that demonstrates the importance of doing careful pharmacokinetic studies in children.
22. Pediatric Network for the Treatment of AIDS (PENTA): Comparison of dual nucleoside-analogue reverse-transcriptase inhibitor regimens with and without nelfinavir in children with HIV-1 who have not previously been treated: the PENTA 5 randomised trial. Lancet 2002, 359:733-740. A well-performed randomized trial that demonstrates the benefits of ABC as first-line therapy in combinations, although awareness of management of ABC hypersensitivity syndrome continues to be important in order to appropriately administer this useful drug.