Parental of caregiver refusal to commence ART require a multidisciplinary assessment to evaluate and overcome barriers to commencing ART. Paediatric HIV health care providers should seek guidance from their respective Child Protection Unit in addressing ongoing concerns regarding ART refusal.
|Rating of Recommendations: A = Strong; B = Moderate; C = Optional|
Rating of Evidence: I = One or more randomized trials in children† with clinical outcomes and/or validated endpoints;
I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children† from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children† with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children† from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion
†Studies that include children or children/adolescents, but not studies limited to postpubertal adolescents
In Australia, follow-up for infants aged <12 months should be provided monthly over the first 6 months at a minimum.
Older children should preferably be aware of why they are taking medications. Timing of HIV disclosure in relation to commencing ART needs to be considered.
Australian clinicians may also use the WHO immunological staging criteria, which classifies age-related CD4 values into four categories – mild, moderate, advanced and severe.
Please refer to WHO immunological staging criteria, Table 2, page 15.
The Panel on Antiretroviral Therapy and Medical Management of Children Living With HIV (the Panel) recommends initiating treatment for all children with HIV studies have shown a benefit to early antiretroviral therapy (ART) initiation,1-3 and that ART initiation within the first year of life is associated with reduced size of viral reservoirs. Treatment initiation in young infants with HIV during the early stages of infection may control viral replication before HIV can evolve into diverse and potentially more pathogenic quasi-species.5 Initiation of therapy at higher CD4 T lymphocyte (CD4) counts has been associated with the presence of fewer drug-resistant mutations at virologic failure in adults.6 Early therapy preserve immune function and prevent clinical disease progression persistent inflammation of cardiovascular, kidney, and liver disease and malignancy.10,11
Rapid treatment initiation, defined as therapy initiated immediately or within days of HIV diagnosis, is recommended except
Survival and Health Benefits Associated With Early Initiation of Antiretroviral Therapy
The Children with HIV Early Antiretroviral Therapy (CHER) trial was a randomized clinical trial in South Africa that initiated ART in infants who were aged 6 to 12 weeks normal CD4 percentages (>25%). Immediate initiation of ART resulted in a 75% reduction in early mortality among these infants, compared with delayed treatment until the infants met clinical or immune criteria. Consistent with the CHER trial, data from a number of observational studies in the United States, Europe, and South Africa demonstrated that infants who received early treatment were less likely to progress to AIDS or death, and they also had improved growth compared with those who started treatment later.14-17
In general, studies that evaluate later initiation of ART in children have a selection bias, because children with perinatal infection and rapidly progressing disease may have died prior to receiving an HIV diagnosis or ART, and children who present later for ART initiation may be slower progressors with a better prognosis. However, in the multicenter, open-label Pediatric Randomised Early versus Deferred Initiation in Cambodia and Thailand (PREDICT) trial, which randomized 300 children with HIV aged 1 year to 12 years at enrollment (median age 6.4 years) to immediately initiate ART or to defer treatment until their CD4 percentage was <15%, better height gain among children who started ART immediately. Similarly, other studies have reported an association between younger age at initiation of ART and more rapid growth reconstitution.15,19-21 Studies conducted in and outside the United States have reported an association between delayed ART initiation and delay of pubertal development and menarche.22 Finally, among 32 youths with perinatally acquired HIV from the Pediatric HIV/AIDS Cohort Study (PHACS), DNA methylation evaluating epigenetic aging was compared to chronologic aging over time. Higher viral load and lower CD4 count were associated with epigenetic aging that exceeded chronologic aging, highlighting the value of achieving early viral suppression and maintaining or reconstituting immune function as close to an HIV diagnosis as possible.23 visceral fat, lipids, and insulin resistance.11
Neurodevelopmental Benefits Associated With Early Initiation of Antiretroviral Therapy
A CHER trial substudy found that infants who initiated ART early had significantly better gross motor and neurodevelopmental profiles than those whose therapy was deferred.24 In a cohort from Thailand, the prevalence of global developmental impairment was 22% (95% confidence
interval [CI], 11% to 27%) among children with HIV who initiated ART within 3 months of birth, compared with 44% (95% CI, 23% to 66%) among children who initiated ART from 3 to
12 months.25 A study of South African infants with perinatal HIV infection who initiated ART within 21 days of life (median 6 days) found that neurodevelopmental scores at 11 months of age for these infants were within the normal range.26
Immune Benefits Associated With Early Initiation of Antiretroviral Therapy
In the CHER study, infants who were treated early had decreased immune activation, greater recovery of CD4 cells, expanded CD4-naive T cells, and retention of innate effector frequencies, resulting in greater immune reconstitution than that achieved in infants who received deferred ART.9 In a small study in Botswana, infants who initiated ART within the first 7 days of life were found to have decreased immune activation, a more polyfunctional HIV-1-specific CD8 cell response, and a markedly reduced HIV latent reservoir, compared with infants who initiated ART later in the first year of life.27 Available data suggest that both children and adults who initiate treatment with a higher CD4 percentage or CD4 count have better immune recovery than patients who initiate treatment with lower CD4 percentages or CD4 counts.20,28-30 Among 1,236 children with perinatally acquired HIV in the United States, only 36% of those who started ART with CD4 percentages <15% achieved CD4 percentages >25% after 5 years of therapy, compared with 59% of children who started with CD4 percentages of 15% to 24%.31 Finally, earlier age at ART initiation results in higher rates of CD4:CD8 ratio normalization and improved immunogenicity of childhood vaccines.32-34
Early initiation of suppressive ART (i.e., in infants aged <6 months) results in a significant proportion of infants with HIV who fail to produce their own HIV-specific antibodies. These infants appear to be HIV-seronegative when tested; however, viral reservoirs remain, and viral rebound occurs if ART is stopped.35-40
Viral Suppression and Viral Reservoirs With Early Initiation of Antiretroviral Therapy
Early initiation of ART within the first 7 days of life, compared with initiation between 8 and 28 days of life, resulted in a fourfold faster time to viral suppression among infants in a multinational study.41 Studies that compared the size of viral reservoirs in children who initiated ART before age 12 weeks with those in children who initiated ART at ≥12 weeks to ≤2 years of age found that viral reservoir size after 1 year and 4 years of ART significantly correlated with age at ART initiation and age at viral control.42-44 Among children in the Early-treated Perinatally HIV-infected Individuals: Improving Children’s Actual Life with Novel Immunotherapeutic Strategies (EPIICAL) Consortium who initiated ART before 2 years of age and maintained a viral load <50 copies/mL for more than 5 years, total HIV-1 DNA levels measured at a median of 12 years after treatment initiation (interquartile range 7.3–15.4), with younger age and viral load at the time of ART initiation each associated with lower reservoir levels.45 Finally, in the CHER study, early ART initiation and longer duration of ART was associated with lower proviral DNA levels at age 5 years.46
These findings suggest that initiating ART soon after an infant acquires HIV can limit the size of the HIV viral reservoir, and smaller reservoirs provide some level of protection against viral rebound in the setting of treatment nonadherence—a frequent event for infants with HIV who are destined for lifelong treatment. Furthermore, have been reported in infants who initiated ART early and who had sustained control of plasma viremia.35,47
The report of a prolonged remission in a child with perinatally acquired HIV in Mississippi generated discussion about early initiation of ART as presumptive treatment in newborns at high risk of HIV acquisition.48,49 and no detectable replication competent virus.50 A French child was treated with ART from 3 months
These experiences have prompted increasing support for initiating treatment as soon as the diagnosis is made, and if possible, during the first weeks of life to limit reservoir formation and possibly facilitate ART-free remission. Although a limited number of case reports describe lengthy remissions in children with perinatally acquired HIV who have undergone treatment interruption, current ART regimens have not been shown to eradicate HIV infection, because HIV persists in CD4 cells and other long-lived cells.50-53 For these reasons, the Panel does not recommend empiric treatment interruption outside of a clinical trial setting.
Managing treatment in neonates with HIV is complex from a medical and social perspective. Because of limited safety and pharmacokinetic (PK) data for ARV drugs in full-term infants aged <2 weeks and preterm infants aged ≤4 weeks, drug and dose selection in this age group is challenging54,55 (see What to Start and Antiretroviral Management of Newborns With Perinatal HIV Exposure or HIV Infection). Hepatic and renal function are immature in newborns who are undergoing rapid maturational changes during the first few months of life, which can result in substantial differences in ARV dose requirements between young infants and older children.56,57 When drug concentrations are subtherapeutic—either because of inadequate dosing, poor absorption, or incomplete adherence—ARV drug resistance can develop rapidly, particularly in young infants who experience high levels of viral replication. Frequent follow-up for dose optimization during periods of rapid growth is especially important when treating young infants. Furthermore, clinicians should continually assess a patient’s adherence and address potential barriers to adherence during this time (see Adherence to Antiretroviral Therapy in Children and Adolescents With HIV).
The Panel recommends rapid initiation of ART (defined as initiating ART immediately or within days of HIV diagnosis) for all children who receive an HIV diagnosis, The urgency of rapid ART initiation is especially critical for children aged <1 year who carry the highest risk of rapid disease progression and mortality. in ART-naive children and adolescents with disease, the Panel recommends initiation of treatment for the opportunistic infection first, ahead of ART initiation (See Guidelines for the Prevention and Treatment of Opportunistic Infections in Children With and Exposed to HIV). Timing of ART initiation in these cases should be discussed with a pediatric HIV specialist.
ART initiation, it is important to assess and discuss issues associated with adherence with caregivers and, when developmentally appropriate, with children. Intensive follow-up during the first few weeks to months after ART initiation is also recommended to support the child and caregiver. Medication adherence is the core requirement for successful virologic control. The Panel recognizes that achieving consistent adherence in children is often challenging.58,59 Incomplete adherence leads to loss of viral control and the selection of drug-resistant mutations, but forcibly administrating ARV drugs to younger children may result in treatment aversion, which often persists into adulthood.
- Schomaker M, Leroy V, Wolfs T, et al. Optimal timing of antiretroviral treatment initiation in HIV-positive children and adolescents: a multiregional analysis from Southern Africa, West Africa and Europe. Int J Epidemiol. 2017;46(2):453-465. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27342220.
- Violari A, Cotton MF, Gibb DM, et al. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med. 2008;359(21):2233-2244. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19020325.
- Shiau S, Strehlau R, Technau KG, et al. Early age at start of antiretroviral therapy associated with better virologic control after initial suppression in HIV-infected infants. AIDS. 2017;31(3):355-364. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27828785.
- Massanella M, Puthanakit T, Leyre L, et al. Continuous prophylactic antiretrovirals/antiretroviral therapy since birth reduces seeding and persistence of the viral reservoir in children vertically infected with human immunodeficiency virus. Clin Infect Dis. 2021;73(3):427-438. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32504081.
- Persaud D, Ray SC, Kajdas J, et al. Slow human immunodeficiency virus type 1 evolution in viral reservoirs in infants treated with effective antiretroviral therapy. AIDS Res Hum Retroviruses. 2007;23(3):381-390. Available at: https://www.ncbi.nlm.nih.gov/pubmed/17411371.
- Palumbo PJ, Fogel JM, Hudelson SE, et al. HIV drug resistance in adults receiving early vs. delayed antiretroviral therapy: HPTN 052. J Acquir Immune Defic Syndr. 2018;77(5):484-491. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29293156.
- Rinaldi S, Pallikkuth S, Cameron M, et al. Impact of early antiretroviral therapy initiation on HIV-specific CD4 and CD8 T cell function in perinatally infected children. J Immunol. 2020;204(3):540-549. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31889024.
- Planchais C, Hocqueloux L, Ibanez C, et al. Early antiretroviral therapy preserves functional follicular helper T and HIV-specific B cells in the gut mucosa of HIV-1- infected individuals. J Immunol. 2018;200(10):3519-3529. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29632141.
- Azzoni L, Barbour R, Papasavvas E, et al. Early ART results in greater immune reconstitution benefits in HIV-infected infants: working with data missingness in a longitudinal dataset. PLoS One. 2015;10(12):e0145320. Available at: https://pubmed.ncbi.nlm.nih.gov/26671450.
- Centers for Disease Control and Prevention. Revised surveillance case definition for HIV infection—United States, 2014. MMWR Recomm Rep. 2014;63(RR-03):1-10. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24717910.
- Centers for Disease Control and Prevention. 1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR. 1994;43(RR-12):1-10. Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/00032890.htm.
- Goetghebuer T, Le Chenadec J, Haelterman E, et al. Short- and long-term immunological and virological outcome in HIV-infected infants according to the age at antiretroviral treatment initiation. Clin Infect Dis. 2012;54(6):878-881. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22198788.
- Shiau S, Arpadi S, Strehlau R, et al. Initiation of antiretroviral therapy before 6 months of age is associated with faster growth recovery in South African children perinatally infected with human immunodeficiency virus. J Pediatr. 2013;162(6):1138-1145 e1132. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23312691.
- Iyun V, Technau KG, Eley B, et al. Earlier antiretroviral therapy initiation and decreasing mortality among HIV-infected infants initiating antiretroviral therapy within 3 months of age in South Africa, 2006–2017. Pediatr Infect Dis J. 2020;39(2):127-133. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31725119.
- Tagarro A, Dominguez Rodriguez S, Violari A, et al. Poor outcome in early treated HIV perinatally infected infants in Africa. Abstract 806. Presented at: Conference on Retroviruses and Opportunistic Infections 2020. Boston, Massachusetts. Available at: https://www.croiconference.org/abstract/poor-outcome-in-early-treated-hiv-perinatally- infected-infants-in-africa.
- Puthanakit T, Saphonn V, Ananworanich J, et al. Early versus deferred antiretroviral therapy for children older than 1 year infected with HIV (PREDICT): a multicentre, randomised, open-label trial. Lancet Infect Dis. 2012;12(12):933-941. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23059199.
- McGrath CJ, Chung MH, Richardson BA, Benki-Nugent S, Warui D, John-Stewart Younger age at HAART initiation is associated with more rapid growth reconstitution. AIDS. 2011;25(3):345-355. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21102302.
- Simms V, Rylance S, Bandason T, et al. CD4+ cell count recovery following initiation of HIV antiretroviral therapy in older childhood and adolescence. AIDS. 2018;32(14):1977- 1982. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29927784.
- Traisathit P, Urien S, Le Coeur S, et al. Impact of antiretroviral treatment on height evolution of HIV infected children. BMC Pediatr. 2019;19(1):287. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31421667.
- Mwambenu B, Ramoloko V, Laubscher R, Feucht U. Growth and the pubertal growth spurt in South African adolescents living with perinatally-acquired HIV infection. PLoS One. 2022;17(1):e0262816. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35077489.
- Shiau S, Brummel SS, Kennedy EM, et al. Longitudinal changes in epigenetic age in youth with perinatally acquired HIV and youth who are perinatally HIV-exposed uninfected. AIDS. 2021;35(5):811-819. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33587437.
- Tarancon-Diez L, Rull A, Herrero P, et al. Early antiretroviral therapy initiation effect on metabolic profile in vertically HIV-1-infected children. J Antimicrob Chemother. 2021;76(11):2993-3001. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34463735.
- Dobe IS, Mocumbi AO, Majid N, Ayele B, Browne SH, Innes S. Earlier antiretroviral initiation is independently associated with better arterial stiffness in children living with perinatally acquired HIV with sustained viral suppression in Mozambique. South Afr J HIV Med. 2021;22(1):1282. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34858652.
- Laughton B, Cornell M, Grove D, et al. Early antiretroviral therapy improves neurodevelopmental outcomes in infants. AIDS. 2012;26(13):1685-1690. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22614886.
- Jantarabenjakul W, Chonchaiya W, Puthanakit T, et al. Low risk of neurodevelopmental impairment among perinatally acquired HIV-infected preschool children who received early antiretroviral treatment in Thailand. J Int AIDS Soc. 2019;22(4):e25278. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30990969.
- Laughton B, Naidoo S, Dobbels E, et al. Neurodevelopment at 11 months after starting antiretroviral therapy within 3 weeks of life. South Afr J HIV Med. 2019;20(1):1008. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31745434.
- Garcia-Broncano P, Maddali S, Einkauf KB, et al. Early antiretroviral therapy in neonates with HIV-1 infection restricts viral reservoir size and induces a distinct innate immune profile. Sci Transl Med. 2019;11(520). Available at: https://www.ncbi.nlm.nih.gov/pubmed/31776292.
- Picat MQ, Lewis J, Musiime V, et al. Predicting patterns of long-term CD4 reconstitution in HIV-infected children starting antiretroviral therapy in sub-Saharan Africa: a cohort- based modelling study. PLoS Med. 2013;10(10):e1001542. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24204216.
- Le T, Wright EJ, Smith DM, et al. Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy. N Engl J Med. 2013;368(3):218-230. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23323898.
- Desmonde S, Dicko F, Koueta F, et al. Association between age at antiretroviral therapy initiation and 24-month immune response in West-African HIV-infected children. AIDS. 2014;28(11):1645-1655. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24804858.
- Patel K, Hernan MA, Williams PL, et al. Long-term effectiveness of highly active antiretroviral therapy on the survival of children and adolescents with HIV infection: a 10-year follow-up study. Clin Infect Dis. 2008;46(4):507-515. Available at: https://www.ncbi.nlm.nih.gov/pubmed/18199042.
- Seers T, Vassallo P, Pollock K, Thornhill JP, Fidler S, Foster C. CD4:CD8 ratio in children with perinatally acquired HIV-1 infection. HIV Med. 2018;19(9):668-672. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30084150.
- Moonsamy S, Suchard M, Madhi SA. Effect of HIV-exposure and timing of anti- retroviral treatment on immunogenicity of trivalent live-attenuated polio vaccine in infants. PLoS One. 2019;14(4):e0215079. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31002702.
- Pensieroso S, Cagigi A, Palma P, et al. Timing of HAART defines the integrity of memory B cells and the longevity of humoral responses in HIV-1 vertically-infected children. Proc Natl Acad Sci U S A. 2009;106(19):7939-7944. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19416836.
- Ananworanich J, Puthanakit T, Suntarattiwong P, et al. Reduced markers of HIV persistence and restricted HIV-specific immune responses after early antiretroviral therapy in children. AIDS. 2014;28(7):1015-1020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24384692.
- Payne H, Mkhize N, Otwombe K, et al. Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the children with HIV early antiretroviral therapy (CHER) trial: a retrospective analysis. Lancet Infect Dis. 2015;15(7):803-809. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26043884.
- Kuhn L, Schramm DB, Shiau S, et al. Young age at start of antiretroviral therapy and negative HIV antibody results in HIV-infected children when suppressed. AIDS. 2015;29(9):1053-1060. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25870988.
- Butler KM, Gavin P, Coughlan S, et al. Rapid viral rebound after 4 years of suppressive therapy in a seronegative HIV-1 infected infant treated from birth. Pediatr Infect Dis J. 2015;34(3):e48-51. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25742088.
- Wamalwa D, Benki-Nugent S, Langat A, et al. Treatment interruption after 2-year antiretroviral treatment initiated during acute/early HIV in infancy. AIDS. 2016;30(15):2303-2313. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27177316.
- Veldsman KA, Laughton B, Janse van Rensburg A, et al. Viral suppression is associated with HIV-antibody level and HIV-1 DNA detectability in early treated children at 2 years of age. AIDS. 2021;35(8):1247-1252. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34076614.
- Dominguez-Rodriguez S, Tagarro A, Palma P, et al. Reduced time to suppression among neonates with HIV initiating antiretroviral therapy within 7 days after birth. J Acquir Immune Defic Syndr. 2019;82(5):483-490. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31714427.
- McManus M, Mick E, Hudson R, et al. Early combination antiretroviral therapy limits exposure to HIV-1 replication and cell-associated HIV-1 DNA levels in infants. PLoS One. 2016;11(4):e0154391. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27104621.
- Martinez-Bonet M, Puertas MC, Fortuny C, et al. Establishment and replenishment of the viral reservoir in perinatally HIV-1-infected children initiating very early antiretroviral therapy. Clin Infect Dis. 2015;61(7):1169-1178. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26063721.
- van Zyl GU, Bedison MA, van Rensburg AJ, Laughton B, Cotton MF, Mellors JW. Early antiretroviral therapy in South African children reduces HIV-1-infected cells and cell- associated HIV-1 RNA in blood mononuclear cells. J Infect Dis. 2015;212(1):39-43. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25538273.
- Foster C, Dominguez-Rodriguez S, Tagarro A, et al. The CARMA study: early infant antiretroviral therapy-timing impacts on total HIV-1 DNA quantitation 12 years later. J Pediatric Infect Dis Soc. 2021;10(3):295-301. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32678875.
- Payne H, Chan MK, Watters SA, et al. Early ART-initiation and longer ART duration reduces HIV-1 proviral DNA levels in children from the CHER trial. AIDS Res Ther. 2021;18(1):63. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34587974.
- Bitnun A, Samson L, Chun TW, et al. Early initiation of combination antiretroviral therapy in HIV-1-infected newborns can achieve sustained virologic suppression with low frequency of CD4+ T cells carrying HIV in peripheral blood. Clin Infect Dis. 2014;59(7):1012-1019. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24917662.
- Violari A, Cotton MF, Kuhn L, et al. A child with perinatal HIV infection and long-term sustained virological control following antiretroviral treatment cessation. Nat Commun. 2019;10(1):412. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30679439.
- Frange P, Faye A, Avettand-Fenoel V, et al. HIV-1 virological remission lasting more than 12 years after interruption of early antiretroviral therapy in a perinatally infected teenager enrolled in the French ANRS EPF-CO10 paediatric cohort: a case report. Lancet HIV. 2016;3(1):e49-54. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26762993.
- Shiau S, Abrams EJ, Arpadi SM, Kuhn L. Early antiretroviral therapy in HIV-infected infants: can it lead to HIV remission? Lancet HIV. 2018;5(5):e250-e258. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29739699.
- Koofhethile CK, Moyo S, Kotokwe KP, et al. Undetectable proviral deoxyribonucleic acid in an adolescent perinatally infected with human immunodeficiency virus-1C and on long-term antiretroviral therapy resulted in viral rebound following antiretroviral therapy termination: a case report with implications for clinical care. Medicine (Baltimore). 2019;98(47):e18014. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31764816.
- Cotton MF, Holgate S, Nelson A, Rabie H, Wedderburn C, Mirochnick M. The last and first frontier—emerging challenges for HIV treatment and prevention in the first week of life with emphasis on premature and low birth weight infants. J Int AIDS Soc. 2015;18(Suppl 6):20271. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26639118.
- Clarke DF, Penazzato M, Capparelli E, et al. Prevention and treatment of HIV infection in neonates: evidence base for existing WHO dosing recommendations and implementation considerations. Expert Rev Clin Pharmacol. 2018;11(1):83-93. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29039686.
- Bekker A, Capparelli EV, Violari A, et al. Abacavir dosing in neonates from birth to 3 months of life: a population pharmacokinetic modelling and simulation study. Lancet HIV. 2022;9(1):e24-e31. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34883066.
- Chadwick EG, Yogev R, Alvero CG, et al. Long-term outcomes for HIV-infected infants less than 6 months of age at initiation of lopinavir/ritonavir combination antiretroviral therapy. AIDS. 2011;25(5):643-649. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21297419.
- Hazra R, Siberry GK, Mofenson LM. Growing up with HIV: children, adolescents, and young adults with perinatally acquired HIV infection. Annu Rev Med. 2010;61:169-185. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19622036.
- Simoni JM, Montgomery A, Martin E, New M, Demas PA, Rana S. Adherence to antiretroviral therapy for pediatric HIV infection: a qualitative systematic review with recommendations for research and clinical management. Pediatrics. 2007;119(6):e1371- 1383. Available at: https://www.ncbi.nlm.nih.gov/pubmed/17533177.