Puberty in perinatal HIV-1 infection: a multicentre longitudinal study of 212 children

Martino, Maurizio de; Tovo, Pier-Angelo; Galli, Luisa; Gabiano, Clara; Chiarelli, F; Zappa, Marco; Gattinara, Guido Castelli; Bassetti, Dante; Giacomet, Vania; Chiappini, Elena; Duse, Marzia; Garetto, Stefano; Caselli, Desireé; Children, Italian Register for Hiv Infection in

doi:10.1097/00002030-200108170-00010

Cited by 61 publications

(73 citation statements)

References 25 publications

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“…31,[34][35][36] No relevant alteration in endocrinologic parameters was found in previous studies. 35 Protease-containing regimens have demonstrated a more profound effect on growth, especially in children who reached undetectable pVL and in those with advanced disease at baseline.…”

Section: Figurementioning

confidence: 69%

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Long-term Experience With Combination Antiretroviral Therapy That Contains Nelfinavir for up to 7 Years in a Pediatric Cohort

Scherpbier

Bekker

Leth³

et al. 2006

Pediatrics

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OBJECTIVE. We sought to provide long-term data on the clinical, immunologic, and virologic response to highly active antiretroviral therapy in infants and children who are naive to protease inhibitors.METHODS. HIV-1-infected children who were naive to protease inhibitors were treated with a combination of nelfinavir and 2 nucleoside reverse transcriptase inhibitors (stavudine and lamivudine) in an observational, prospective, singlecenter study. Virologic failure-free survival was assessed by Kaplan-Meier analyses. The increase in CD4 ϩ T cells during follow-up was estimated with a generalized linear model incorporating repeated measurements.RESULTS. Thirty-nine HIV-1-infected children were included and followed for a median period of 227 weeks (interquartile range: 108 -275 weeks). The virologic failure-free survival rate was 74%, 66%, 58%, and 54% after 48, 96, 144, and 240 weeks, respectively. Children who experienced virologic failure in 48 weeks (or 96 weeks) were younger at baseline compared with the responders (0.8 vs 5.3 years). Eighteen children remained on the regimen for Ͼ5 years. All children, including the nonresponders, showed a sustained immunologic response. Grades 3 to 4 toxicity was observed in 2 patients only. Eleven developed clinically evident lipodystrophy.CONCLUSION. Combination therapy can be used safely in infants and children over a long period. Young age is strongly associated with virologic failure. Although the virologic response declined, immunologic parameters and clinical improvement were sustained up to 7 years, at the expense of lipodystrophy. [1][2][3] Mortality, disease progression, and hospital admissions in HIV-infected children have declined substantially since the introduction of highly active antiretroviral therapy (HAART), just as has been seen in adults. [4][5][6] In adults, it was shown that most patients had changed their first regimen after 4 years of HAART because of virologic failure and the availability of alternative drug regimens. In adults, a continued increase in CD4 ϩ T cell count was seen in patients who experienced sustained virologic suppression. 7,8 However, one cannot extrapolate results in adults to children because of differences in immunity (eg, the immaturity of the immune system and larger thymic output); in pharmacokinetics and pharmacodynamics of antiretroviral drugs in infants and children; and, most important, in formulation, availability of drugs, and strict adherence to therapy. Studies have shown that the age-adjusted CD4 ϩ T-cell numbers increase in infants and children, especially in the more immunocompromised ones, even when failing in viral suppression. 9 Despite reasonably good virologic response rates at 48 and 96 weeks of HAART, data from several pediatric studies have shown that the virologic response in children is less prominent compared with adults. 1,3,[9][10][11][12][13][14] Infants and children often start antiretroviral therapy at very young ages and have to use their medication lifelong. Hence, there is an urgent need ...

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Section: Figurementioning

confidence: 69%

“…32,33 HIV infection may interfere with sexual maturation and the onset of puberty. 34 This could influence especially the growth velocity. However, in our cohort, the median age at start of HAART was 4.7 years (IQR: 1.1-8.8 years); leaving out the oldest quartile from the analysis, similar growth parameters were obtained (data not shown).…”

Section: E534mentioning

confidence: 99%

Long-term Experience With Combination Antiretroviral Therapy That Contains Nelfinavir for up to 7 Years in a Pediatric Cohort

Scherpbier

Bekker

Leth³

et al. 2006

Pediatrics

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“…Our data related to the age at puberty onset, compared with our previous data in 1,664 Caucasian healthy children [6], evidenced that age was significantly delayed [years (95% CI)] both in girls [B2 12.7 (12.0–13.3), B3 13.4 (12.7–14.2) and B4 14.4 (13.9–15.3 years)] and boys [G2 12.1 (11.5–12.7), G3 13.6 (13.2–14.0) and G4 14.8 (14.2–15.8 years).…”

Section: Resultsmentioning

confidence: 87%

“…As a whole, according to the European Collaborative Study, during a 10-year follow-up, infected children were on average 7 kg lighter and 7.5 cm shorter than uninfected children [1]. In addition, children with perinatal HIV infection experience delays both in the age of onset of puberty and in their progression through the Tanner stages [6]. Children with relevant immunodeficiency tend to have the most significant delays in pubertal development [7].…”

Section: Introductionmentioning

confidence: 99%

Final Height in Patients Perinatally Infected with the Human Immunodeficiency Virus

et al. 2010

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Introduction: Data concerning final height are completely lacking in human immunodeficiency virus (HIV)-infected children. Design: Retrospective evaluation of auxological data up to final height in a cohort of patients with perinatal HIV infection. Patients and Methods: In 95 Caucasian patients (57 females and 38 males, median age 17.5 years) the following data were evaluated as standard deviation (SD) score: prepubertal height (PrH), height velocity (HV), final height (FH), target height (TH), FH minus PrH, predicted adult height (PAH), FH minus PAH, and FH minus TH. Results: Patients showed a significantly reduced PrH and FH compared to their TH (p < 0.001), even if no difference was evidenced between PrH and FH. Age at puberty onset displayed a negative significant correlation with PrH (p = 0.002) and CD4+ cell percentage (p < 0.01). Finally, HV displayed a significant correlation with viremia (p = 0.001), but not with CD4+ cell percentage. Conclusions: HIV perinatally infected patients show a FH significantly reduced and not in accordance with TH. Our data seem to suggest that the losses in stature accumulated throughout the total period of childhood and adolescence may contribute to their reduced FH.

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“…This interference might result from direct virus action, secondary infections, nutritional disorders, and the action of cytokines. The delay in sexual maturation seems to be greater in the later pubertal stages [11,12] .…”

Section: Maturationmentioning

confidence: 92%

Perinatally infected adolescents living with human immunodeficiency virus (perinatally human immunodeficiency virus)

Cruz

Cardoso

2015

WJV

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Puberty in perinatal HIV-1 infection: a multicentre longitudinal study of 212 children

Cited by 61 publications

References 25 publications

Long-term Experience With Combination Antiretroviral Therapy That Contains Nelfinavir for up to 7 Years in a Pediatric Cohort

Long-term Experience With Combination Antiretroviral Therapy That Contains Nelfinavir for up to 7 Years in a Pediatric Cohort

Final Height in Patients Perinatally Infected with the Human Immunodeficiency Virus

Perinatally infected adolescents living with human immunodeficiency virus (perinatally human immunodeficiency virus)

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