Antiretroviral therapy for HIV infection in infants and children: towards universal access. Recommendations for a public health approach.

These stand-alone treatment guidelines serve as a framework for selecting the most potent and feasible first-line and second-line ARV regimens as components of expanded national responses for the care of HIV-infected infants and children. Recommendations are provided on: diagnosing HIV infection in infants and children; when to start ART including situations where severe HIV disease in children less than 18 months of age has been presumptively diagnosed; clinical and laboratory monitoring of ART; substitution of ARVs for toxicities. The guidelines consider ART in different situations e.g. where infants and children are coinfected with HIV and TB or have been exposed to ARVs either for the prevention of MTCT (PMTCT) or because of breastfeeding from an HIV-infected mother on ART. They address the importance of nutrition in the HIV-infected child and of severe malnutrition in relation to the provision of ART. Adherence to therapy and viral resistance to ARVs are both discussed with reference to infants and children. A section on ART in adolescents briefly outlines key issues related to treatment in this age group. (excerpt)

[1]  J. Ena,et al.  Risk and determinants of developing severe liver toxicity during therapy with nevirapine-and efavirenz-containing regimens in HIV-infected patients , 2003, International journal of STD & AIDS.

[2]  B. Masquelier,et al.  Prevalence of resistance to nevirapine in mothers and children after single-dose exposure to prevent vertical transmission of HIV-1: a meta-analysis. , 2007, International journal of epidemiology.

[3]  Terri Wrin,et al.  The prevalence of antiretroviral drug resistance in the United States , 2004, AIDS.

[4]  D. Gibb,et al.  Adherence to prescribed antiretroviral therapy in human immunodeficiency virus-infected children in the PENTA 5 trial , 2003, The Pediatric infectious disease journal.

[5]  B. Clotet,et al.  HIV type 1 fitness evolution in antiretroviral-experienced patients with sustained CD4+ T cell counts but persistent virologic failure. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  Nigel Rollins,et al.  Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis , 2004, The Lancet.

[7]  L. Moulton,et al.  Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials , 2008, The Lancet.

[8]  Julio S. G. Montaner,et al.  CD4+ T-Cell Count Monitoring Does Not Accurately Identify HIV-Infected Adults With Virologic Failure Receiving Antiretroviral Therapy , 2008, Journal of acquired immune deficiency syndromes.

[9]  R. Yolken,et al.  Resting energy expenditure and body composition in children with HIV infection. , 1998, Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology.

[10]  S. Mora,et al.  A 12-Month Treatment With Tenofovir Does Not Impair Bone Mineral Accrual in HIV-Infected Children , 2005, Journal of acquired immune deficiency syndromes.

[11]  A. Balasubramanyam,et al.  Dysregulated energy expenditure in HIV-infected patients: a mechanistic review. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[12]  H. Zar,et al.  Detection of tuberculosis in HIV-infected children using an enzyme-linked immunospot assay , 2009, AIDS.

[13]  W. Moss,et al.  Effectiveness of antiretroviral therapy among HIV-infected children in sub-Saharan Africa. , 2008, The Lancet. Infectious diseases.

[14]  Joel E Gallant,et al.  Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. , 2006, The New England journal of medicine.

[15]  D. Bennett,et al.  The World Health Organization's global strategy for prevention and assessment of HIV drug resistance , 2008, Antiviral therapy.

[16]  Nontobeko Mpontshane,et al.  Zinc or Multiple Micronutrient Supplementation to Reduce Diarrhea and Respiratory Disease in South African Children: A Randomized Controlled Trial , 2007, PloS one.

[17]  Mikko Niemi,et al.  Pharmacokinetic Interactions with Rifampicin , 2003, Clinical pharmacokinetics.

[18]  N. Shaffer,et al.  Early Diagnosis of HIV‐1‐Infected Infants in Thailand Using RNA and DNA PCR Assays Sensitive to Non‐B Subtypes , 2000, Journal of acquired immune deficiency syndromes.

[19]  P. Reiss,et al.  Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. , 2008, The Lancet. Infectious diseases.

[20]  J. van den Broeck,et al.  The effect of nutritional support on weight gain of HIV‐infected children with prolonged diarrhoea , 2007, Acta paediatrica.

[21]  S. Hayashi,et al.  Nelfinavir pharmacokinetics in stable human immunodeficiency virus-positive children: Pediatric AIDS Clinical Trials Group Protocol 377. , 2003, Pediatrics.

[22]  R. de Groot,et al.  Treatment with highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children is associated with a sustained effect on growth. , 2002, Pediatrics.

[23]  P. Mcdermott,et al.  Disease progression in children with vertically-acquired HIV infection in sub-Saharan Africa: reviewing the need for HIV treatment. , 2007, Current HIV research.

[24]  B. Eley,et al.  Disseminated bacille Calmette-Guérin disease in HIV-infected South African infants. , 2009, Bulletin of the World Health Organization.

[25]  M. Hughes,et al.  Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1. , 2001, The New England journal of medicine.

[26]  D. Haas Pharmacogenomics and HIV therapeutics. , 2005, The Journal of infectious diseases.

[27]  Alimuddin Zumla,et al.  Impact of HIV infection on tuberculosis , 2000, Postgraduate medical journal.

[28]  D. Katzenstein,et al.  Breast-milk shedding of drug-resistant HIV-1 subtype C in women exposed to single-dose nevirapine. , 2005, The Journal of infectious diseases.

[29]  V. Arendt,et al.  Validation of 2006 WHO Prediction Scores for True HIV Infection in Children Less than 18 Months with a Positive Serological HIV Test , 2009, PloS one.

[30]  M. Sharland,et al.  PENTA guidelines for the use of antiretroviral therapy, 2004 , 2004, HIV medicine.

[31]  J. Giesecke,et al.  Risk factors for human immunodeficiency virus infection in Ethiopian children with tuberculosis , 2001, The Pediatric Infectious Disease Journal.

[32]  L. Aurpibul,et al.  Haematological changes after switching from stavudine to zidovudine in HIV‐infected children receiving highly active antiretroviral therapy , 2008, HIV medicine.

[33]  L. Bahamondes,et al.  Pharmacokinetic interactions between depot medroxyprogesterone acetate and combination antiretroviral therapy. , 2008, Fertility and sterility.

[34]  J. Arribas The rise and fall of triple nucleoside reverse transcriptase inhibitor (NRTI) regimens. , 2004, The Journal of antimicrobial chemotherapy.

[35]  J. Simoni,et al.  Adherence to Antiretroviral Therapy for Pediatric HIV Infection: A Qualitative Systematic Review With Recommendations for Research and Clinical Management , 2007, Pediatrics.

[36]  C. Fletcher,et al.  Switch from ritonavir to indinavir in combination therapy for HIV-1-infected children. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[37]  W. Tsai,et al.  The effects of vitamin A supplementation on the morbidity of children born to HIV-infected women. , 1995, American journal of public health.

[38]  W. Fawzi,et al.  Vitamin A supplements and diarrheal and respiratory tract infections among children in Dar es Salaam, Tanzania. , 2000, The Journal of pediatrics.

[39]  M. Battegay,et al.  Immune reconstitution in HIV-infected patients. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[40]  J. Wang,et al.  Growth velocity, fat-free mass and energy intake are inversely related to viral load in HIV-infected children. , 2000, The Journal of nutrition.

[41]  B. Chi,et al.  Clinical outcomes and CD4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia. , 2007, JAMA.

[42]  G. Maartens,et al.  Effect of Rifampicin on Efavirenz Pharmacokinetics in HIV-Infected Children With Tuberculosis , 2009, Journal of acquired immune deficiency syndromes.

[43]  G. Maartens,et al.  Effect of Rifampicin on Lopinavir Pharmacokinetics in HIV-Infected Children With Tuberculosis , 2008, Journal of acquired immune deficiency syndromes.

[44]  B. Eley,et al.  Tuberculosis during early antiretroviral-induced immune reconstitution in HIV-infected children. , 2007, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[45]  J. Sleasman,et al.  Varicella zoster as a manifestation of immune restoration disease in HIV-infected children. , 2004, The Journal of allergy and clinical immunology.

[46]  S. Hammer,et al.  Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial. , 2001, JAMA.

[47]  M. Batterham Investigating heterogeneity in studies of resting energy expenditure in persons with HIV/AIDS: a meta-analysis. , 2005, The American journal of clinical nutrition.

[48]  G. Gray,et al.  Efficacy of Short-Course AZT Plus 3TC to Reduce Nevirapine Resistance in the Prevention of Mother-to-Child HIV Transmission: A Randomized Clinical Trial , 2009, PLoS medicine.

[49]  James Bethel,et al.  Performance Characteristics of HIV-1 Culture and HIV-1 DNA and RNA Amplification Assays for Early Diagnosis of Perinatal HIV-1 Infection , 2003, Journal of acquired immune deficiency syndromes.

[50]  T. Puthanakit,et al.  Efficacy of highly active antiretroviral therapy in HIV-infected children participating in Thailand's National Access to Antiretroviral Program. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[51]  R. Bollinger,et al.  Nevirapine Resistance and Breast-Milk HIV Transmission: Effects of Single and Extended-Dose Nevirapine Prophylaxis in Subtype C HIV-Infected Infants , 2009, PloS one.

[52]  S. Khoo,et al.  Effects of drugs on 2',3'-dideoxy-2',3'-didehydrothymidine phosphorylation in vitro , 1997, Antimicrobial agents and chemotherapy.

[53]  O. Kirk,et al.  Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration , 2008, The Lancet.

[54]  L. Scott,et al.  Emtricitabine , 2012, Drugs.

[55]  C. Fletcher,et al.  A pilot study of combination therapy with indinavir, stavudine (d4T), and didanosine (ddI) in children infected with the human immunodeficiency virus. , 1998, The Journal of pediatrics.

[56]  S. Lagakos,et al.  Response to antiretroviral therapy after a single, peripartum dose of nevirapine. , 2007, The New England journal of medicine.

[57]  T. Quinn,et al.  Survival from 9 months of age among HIV-infected and uninfected Zambian children prior to the availability of antiretroviral therapy. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[58]  Robert L. Johnson,et al.  Retention, adherence, and compliance: special needs of HIV-infected adolescent girls and young women. , 2003, The Journal of adolescent health : official publication of the Society for Adolescent Medicine.

[59]  P. Keiser,et al.  Comparison of Nevirapine- and Efavirenz-Containing Antiretroviral Regimens in Antiretroviral-Naïve Patients: A Cohort Study , 2002, HIV clinical trials.

[60]  P. Keiser,et al.  Comparison of Efficacy of Efavirenz and Nevirapine: Lessons Learned for Cohort Analysis in Light of the 2NN Study , 2003, HIV Clinical Trials.

[61]  J. Coffin,et al.  HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy , 1995, Science.

[62]  I. Hambleton,et al.  Tuberculosis and HIV co-infections in Jamaican children. , 2004, West Indian medical journal.

[63]  M. Chhagan,et al.  Case management of HIV-infected severely malnourished children: challenges in the area of highest prevalence , 2008, The Lancet.

[64]  J. Church,et al.  A phase I/II evaluation of stavudine (d4T) in children with human immunodeficiency virus infection. , 1995, Pediatrics.

[65]  J. Rossert,et al.  Fanconi syndrome and renal failure induced by tenofovir: a first case report. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[66]  G. Montepiedra,et al.  Immune reconstitution after receipt of highly active antiretroviral therapy in children with advanced or progressive HIV disease and complete or partial viral load response. , 2005, The Journal of infectious diseases.

[67]  C. Chintu,et al.  Tuberculosis in children with human immunodeficiency virus infection. , 2005, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[68]  G. Beall,et al.  Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. , 2002, The New England journal of medicine.

[69]  P. Graaff,et al.  Use of antiretroviral therapy in resource-limited countries in 2006: distribution and uptake of first- and second-line regimens , 2007, AIDS.

[70]  Paige L. Williams,et al.  Toxicities associated with dual nucleoside reverse-transcriptase inhibitor regimens in HIV-infected children. , 2008, The Journal of infectious diseases.

[71]  D. Blaauw,et al.  Diagnosis of paediatric HIV infection in a primary health care setting with a clinical algorithm. , 2003, Bulletin of the World Health Organization.

[72]  H. Kirchner,et al.  High level of discordant IGRA results in HIV-infected adults and children. , 2008, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[73]  E. Carter,et al.  Highly active antiretroviral therapy (HAART) in adults with tuberculosis: current status. , 2005, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[74]  S. Steinberg,et al.  Tenofovir Disoproxil Fumarate and an Optimized Background Regimen of Antiretroviral Agents as Salvage Therapy for Pediatric HIV Infection , 2005, Pediatrics.

[75]  R. Gie,et al.  A Refined Symptom-Based Approach to Diagnose Pulmonary Tuberculosis in Children , 2006, Pediatrics.

[76]  E. Abrams,et al.  The reliability of reports of medical adherence from children with HIV and their adult caregivers. , 2003, Journal of pediatric psychology.

[77]  Stephanie A. Jones,et al.  Can clinical algorithms deliver an accurate diagnosis of HIV infection in infancy? , 2005, Bulletin of the World Health Organization.

[78]  C. Rouzioux,et al.  HIV-1 RNA detection in plasma for the diagnosis of infection in neonates. The French Pediatric HIV Infection Study Group. , 1997, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[79]  N. Sewankambo,et al.  Mortality in HIV-Infected and Uninfected Children of HIV-Infected and Uninfected Mothers in Rural Uganda , 2006, Journal of acquired immune deficiency syndromes.

[80]  D. Hoover,et al.  Resistance after single-dose nevirapine prophylaxis emerges in a high proportion of Malawian newborns , 2005, AIDS.

[81]  O. Ramilo,et al.  Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children , 2003, The Pediatric infectious disease journal.

[82]  S. Zeichner,et al.  Decreased bone mineral density with off-label use of tenofovir in children and adolescents infected with human immunodeficiency virus. , 2008, The Journal of pediatrics.

[83]  J. Park,et al.  Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093. , 2008, Contraception.

[84]  A. Baleta Trial finds simultaneous HIV/tuberculosis treatment beneficial. , 2008, The Lancet. Infectious diseases.

[85]  G. Moyle NNRTI choice: has 2NN changed our practice? , 2003, The AIDS reader.

[86]  V. Soriano,et al.  Incidence of Liver Injury After Beginning Antiretroviral Therapy with Efavirenz or Nevirapine , 2003, HIV clinical trials.

[87]  Christopher D Pilcher,et al.  Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. , 2004, The New England journal of medicine.

[88]  J. Church Immune Reconstitution Syndrome After Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus-Infected Thai Children , 2007, Pediatrics.

[89]  P. Rheenen The use of the paediatric tuberculosis score chart in an HIV-endemic area. , 2002 .

[90]  J. Sterne,et al.  Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries , 2006, The Lancet.

[91]  S. Cohn,et al.  Issues Regarding Use of Hormonal Contraceptives in Clinical Trials of Antiretroviral Therapy , 2005, Journal of acquired immune deficiency syndromes.

[92]  F. Matovu,et al.  Nevirapine resistance in women and infants after first versus repeated use of single-dose nevirapine for prevention of HIV-1 vertical transmission. , 2008, The Journal of infectious diseases.

[93]  D. Faulds,et al.  Nelfinavir. A review of its therapeutic efficacy in HIV infection. , 1998, Drugs.

[94]  W. Nyandiko,et al.  A Systematic Review of Pediatric Adherence to Antiretroviral Therapy in Low- and Middle-Income Countries , 2008, The Pediatric infectious disease journal.

[95]  Alimuddin Zumla,et al.  Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial , 2004, The Lancet.

[96]  C. Dreezen,et al.  The role of non-viral load surrogate markers in HIV-positive patient monitoring during antiviral treatment , 2004, International journal of STD & AIDS.

[97]  T. Wrin,et al.  Longitudinal assessment of immune response and viral characteristics in HIV-infected patients with prolonged CD4(+)/viral load discordance. , 2005, AIDS research and human retroviruses.

[98]  O. Ramilo,et al.  Effect of combination antiretroviral therapy on cerebrospinal fluid HIV RNA, HIV resistance, and clinical manifestations of encephalopathy. , 2002, The Journal of pediatrics.

[99]  Rebecca Hoh,et al.  Interruption of treatment with individual therapeutic drug classes in adults with multidrug-resistant HIV-1 infection. , 2005, The Journal of infectious diseases.

[100]  S. Shelburne,et al.  Immune reconstitution inflammatory syndrome: more answers, more questions. , 2006, The Journal of antimicrobial chemotherapy.

[101]  D. Dunn Short-term risk of disease progression in HIV-1-infected children receiving no antiretroviral therapy or zidovudine monotherapy: a meta-analysis , 2003, The Lancet.

[102]  A. Tomkins,et al.  Nutritional recovery in HIV-infected and HIV-uninfected children with severe acute malnutrition , 2008, Archives of Disease in Childhood.

[103]  E. Abrams,et al.  Care and Treatment of HIV-Infected Children in Africa: Issues and Challenges at the District Hospital Level , 2007, The Pediatric infectious disease journal.

[104]  R. Bunnell,et al.  Disclosure of HIV Status and Adherence to Daily Drug Regimens Among HIV-infected Children in Uganda , 2006, AIDS and Behavior.

[105]  E. Nicastri,et al.  Clinical outcome after 4 years follow‐up of HIV‐seropositive subjects with incomplete virologic or immunologic response to HAART , 2005, Journal of medical virology.

[106]  Ajit Lalvani,et al.  Diagnosis of tuberculosis in South African children with a T cell-based assay: a prospective cohort study , 2004, The Lancet.

[107]  G. Aldrovandi,et al.  Antiretroviral Pharmacokinetics in the Paediatric Population , 2002, Clinical pharmacokinetics.

[108]  D. Boulware,et al.  Pediatric HIV immune reconstitution inflammatory syndrome , 2008, Current opinion in HIV and AIDS.

[109]  Steven C Johnson,et al.  Antiviral activity of lamivudine in salvage therapy for multidrug-resistant HIV-1 infection. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[110]  Bruno Ledergerber,et al.  Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes , 2004, The Lancet.

[111]  R. Chandra,et al.  Nutrition and immunity: an overview. , 1994, The Journal of nutrition.

[112]  J. Volmink,et al.  Treatment of latent tuberculosis infection in HIV infected persons. , 2004, The Cochrane database of systematic reviews.

[113]  M. Sharland,et al.  Triple Nucleoside Reverse Transcriptase Inhibitor Therapy in Children , 2004, Paediatric drugs.

[114]  H. Zar,et al.  Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial , 2006, BMJ : British Medical Journal.

[115]  P. Jeena,et al.  Impact of HIV-1 co-infection on presentation and hospital-related mortality in children with culture proven pulmonary tuberculosis in Durban, South Africa. , 2002, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[116]  C. Pannuti,et al.  Analysis of HIV- type 1 protease and reverse transcriptase in Brazilian children failing highly active antiretroviral therapy (HAART). , 2005, Revista do Instituto de Medicina Tropical de Sao Paulo.

[117]  Paige L. Williams,et al.  Long-term effects of highly active antiretroviral therapy on CD4+ cell evolution among children and adolescents infected with HIV: 5 years and counting. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[118]  Akihiko Saitoh,et al.  Clinical Outcomes After an Unstructured Treatment Interruption in Children and Adolescents With Perinatally Acquired HIV Infection , 2008, Pediatrics.

[119]  Alimuddin Zumla,et al.  Role of co-trimoxazole prophylaxis in reducing mortality in HIV infected adults being treated for tuberculosis: randomised clinical trial , 2008, BMJ : British Medical Journal.

[120]  I. Williams,et al.  Severe renal dysfunction and risk factors associated with renal impairment in HIV-infected adults in Africa initiating antiretroviral therapy. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[121]  D. Droz,et al.  Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[122]  J. van den Broeck,et al.  Effect of micronutrient supplementation on diarrhoeal disease among stunted children in rural South Africa , 2008, European Journal of Clinical Nutrition.

[123]  T. Self,et al.  Rifampin and rifabutin drug interactions: an update. , 2002, Archives of internal medicine.