Lopinavir/ritonavir-based antiretroviral therapy in human immunodeficiency virus type 1-infected naive children: rare protease inhibitor resistance mutations but high lamivudine/emtricitabine resistance at the time of virologic failure.
Frange P, Briand N, Avettand-fenoel V, Veber F, Moshous D, Mahlaoui N, Rouzioux C, Blanche S, Chaix ML.
BACKGROUND
Lopinavir/ritonavir (LPV/r) is now the protease inhibitor regimen of choice in the first-line antiretroviral therapy for children <6 years of age.
METHODS
We included all the human immunodeficiency virus (HIV) type 1-infected highly active antiretroviral therapy (HAART)-naive children who started an LPV/r-based regimen between 2000 and 2009 at the Necker Hospital (Paris, France). Virologic failure (VF) was defined as an HIV-RNA ≥50 copies/mL. Resistance genotypic test was performed in case of VF.
RESULTS
A total of 43 children were included at a median age of 4.8 years (1.8-8.0). Median level of HIV RNA and percentage of CD4 cell count was 5.5 log₁₀ copies/mL (4.6-6) and 15% (8-27.5), respectively. HAART included LPV/r and 2 nucleoside reverse-transcriptase inhibitors, mainly lamivudine (3TC), zidovudine, and/or abacavir. The median follow-up period was 36 months (18-72). Less than 50 copies/mL of HIV RNA was observed in 46%, 67%, and 70% of the children at months 6, 9, and 12, respectively. In all, 20 children (46.5%) experienced a VF. The risk factors of primary VF were a young age and a low socioeconomic status. The genotypic resistance test, performed for 18 of 20 children with VF, revealed 1 LPV/r-resistant virus and protease inhibitor-related major mutations without LPV/r resistance in 2 other children. Of the 18 children with VF, 15 received a 3TC-based HAART: 12 of 15 (80%) harbored a 3TC-resistant virus. No virus resistant to zidovudine or abacavir was found.
CONCLUSION
In all, 70% of HAART-naive children had virologic success at month 12. The selection of LPV-resistant strains was a rare event. A high rate of selection of 3TC-mutations strengthens the recommendation to prefer a first-line 3TC-sparing regimen, particularly for children with risk factors of poor adherence.
Clin Infect Dis. 2010 Oct 1;51(7):833-43.
Mother-to-Child Transmission of HIV-2 Infection from 1986 to 2007 in the ANRS French Perinatal Cohort EPF-CO1
M. Burgard, C. Jasseron, S. Matheron, F. Damond, K. Hamrene, S. Blanche, A. Faye, C. Rouzioux, J. Warszawski, L. Mandelbrot, and the ANRS French Perinatal Cohort EPF-CO1
BACKGROUND
Management of pregnant women with human immunodeficiency virus (HIV) type 2 infection remains unclear because of its low prevalence and important differences from HIV-1.
METHODS
Pregnant women monoinfected with HIV-2 or HIV-1 and their infants enrolled in the prospective, national, multicenter French Perinatal Cohort between 1986 and 2007.
RESULTS
Overall, 2.6% (223/8660) of mothers were infected with HIV-2, and they accounted for 3.1% (367/11841) of the total births. Most were born in sub-Saharan Africa. A higher proportion of HIV-2-infected mothers than HIV-1-infected mothers had no symptoms, had received no antiretroviral threrapy at conception (85.9% vs 66.7%), and had received no antiretroviral therapy during pregnancy (42.8% vs 19.9%), particularly highly active antiretroviral therapy (HAART) (79.7% vs 46.1%), and they had higher CD4 cell counts near delivery (median, 574 vs 452 cells/mm3; P < .01). If antiretroviral therapy was used, it was started at a later gestational age for HIV-2-infected mothers (median, 28 vs 25 weeks; P < .01). HIV-2-infected mothers were more likely to deliver vaginally (67.9% vs 49.3%) and to breastfeed (3.6% vs 0.6%; P < .01), and their infants less frequently received postexposure prophylaxis. In the period 2000–2007, the proportion with viral load <100 copies/mL at delivery was 90.5% of HIV-2-infected mothers, compared with 76.2% of HIV-1-infected mothers (P = .1). There were 2 cases of transmission: 1 case in 1993 occurred following maternal primary infection, and the other case occurred postnatally in 2002 and involved a mother with severe immune deficiency. The mother-to-child transmission rate for HIV-2 was 0.6% (95% confidence interval, 0.07%–2.2%).
CONCLUSIONS
Care for HIV-2-infected pregnant women rests on expert opinion. The mother-to-child transmission residual rate (0.07%–2.2%) argues for systematic treatment: protease inhibitor-based HAART for women requiring antiretroviral therapy or for primary infection and simplified prevention of mother-to-child transmission in other instances.
Clin Infect Dis. 2010 Jul 15;51(2):214-24
Long-Term Outcomes in Adolescents Perinatally Infected with HIV-1 and Followed Up since Birth in the French Perinatal Cohort (EPF/ANRS CO10)
C. Dollfus, J. Le Chenadec, A. Faye, S. Blanche, N. Briand, C. Rouzioux, and J. Warszawski
BACKGROUND
Increasing numbers of children perinatally infected with human immunodeficiency virus (HIV) are reaching adolescence, largely because of advances in treatment over the past 10 years, but little is known about their current health status. We describe here the living conditions and clinical and immunovirologic outcomes at last evaluation among this pioneering generation of adolescents who were born before the introduction of prophylaxis for vertical transmission and whose infections were diagnosed at a time when treatment options were limited.
METHODS
The eligible population consisted of HIV-1—infected children who were born before December 1993 and who were included at birth in the prospective national French Perinatal Cohort (EPF/ANRS CO10).
RESULTS
Of the 348 eligible children, 210 (60%; median age, 15 years) were still alive and regularly followed up. Current treatment was highly active antiretroviral therapy (HAART) in 77% and 2 nucleoside analogues in 5.0%; 16% had stopped treatment, and 2% had never been treated. The median CD4 cell count was 557 cells/µL, and 200 cells/µL was exceeded in 94% of patients. The median viral load was 200 copies/mL. Viral load was undetectable in 43% of the adolescents and in 54.5% of those receiving HAART. Median height, weight, and body mass index were similar to French reference values for age, and school achievement was similar to nationwide statistics. Better immunologic status was associated with being younger and with having begun HAART earlier. Undetectable viral load was associated with maternal geographic origin and current HAART.
CONCLUSIONS
Given the limited therapeutic options available during the early years of these patients' lives and the challenge presented by treatment adherence during adolescence, the long-termoutcomes among this population are encouraging.
Clin Infect Dis. 2010 ;50(4): 585-96
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