Viral Load and Disease Progression in Infants Infected with Human Immunodeficiency Virus Type 1

Shearer, William T.; Quinn, Thomas C.; LaRussa, Philip; Lew, Judy; Mofenson, Lynne; Almy, Susan; Rich, Kenneth; Handelsman, Edward; Díaz, Clemente; Pagano, Marcello; Smeriglio, Vincent L.; Kalish, Leslie A.

doi:10.1056/nejm199705083361901

Cited by 500 publications

(278 citation statements)

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“…9,10 Most of these adult studies were performed in the pre-HAART era [6][7][8][9][10] and the timing of HIV infection (adults vs. infants) and immune ontogeny (developed vs. developing) most likely explains the lack of complete agreement. One clear example of the difference between pediatric adult HIV pathogenesis is the rapid rise and persistent (≥3 years) elevation in HIV RNA level (hundred thousand to million range) in newborns 26 compared to a much lower HIV viral set-point observed 6-8 weeks after infection in adults.…”

Section: Discussionmentioning

confidence: 99%

Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study

Foster

McIntosh

Thompson

et al. 2008

Journal of Allergy and Clinical Immunology

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Section: Discussionmentioning

confidence: 99%

Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study

Foster

McIntosh

Thompson

et al. 2008

Journal of Allergy and Clinical Immunology

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“…Although children have higher viral burdens than adults, which would predict more rapid disease progression and a poorer prognosis [11], they exhibit a higher degree of responsiveness to therapy in terms of CD4 + T-lymphocyte reconstitution when compared with adults [12]. These findings suggest that the dynamics of immunoreconstitution is different in children.…”

Section: Introductionmentioning

confidence: 99%

Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure

Peruzzi

Azzari

Galli

et al. 2002

Clinical and Experimental Immunology

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SUMMARY To analyse the effect of highly active antiretroviral therapy (HAART) on T-lymphocyte functions we selected seven HIV-1 perinatally infected children (CDC immunological category 1 or 2) who had neither a fall in their plasma HIV-1 RNA levels nor a significant rise in CD4+ lymphocyte counts while receiving HAART. Clinical signs and symptoms were monitored monthly. Plasma viral load, CD4+, CD8+, CD19+ lymphocyte counts and in vitro T-lymphocyte proliferative responses to mitogens (anti-CD3, phytohaemoagglutinin, concanavalin A and pokeweed mitogen) and recall antigens (Candida albicans and tetanus toxoid) were tested at baseline and after 1, 3, 6 and 12 months of HAART. Twenty-two healthy age-matched children were studied as controls. A gain in body weight, no worsening of the disease and no recurrence of opportunistic infections were observed. At baseline, the majority of the children had low responses to mitogens, and all of them had a defective in vitro antigen-specific T-lymphocyte response (<2 standard deviations below the mean result for controls). During HAART, a significant increase in the response to mitogens and antigens was observed in all the patients. The T-lymphocyte response was restored more consistently against antigens to which the immune system is constantly exposed (Candida albicans, baseline versus 12 months: P < 0·001) compared with a low-exposure antigen (tetanus toxoid, baseline versus 12 months: P < 0·01). HAART restores in vitro T-lymphocyte responses even in the absence of a significant viral load decrease and despite any significant increase in CD4+ lymphocyte counts. It implies that a direct mechanism might be involved in the overall immune recovery under HAART.

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“…Their median age was 14.5 y (interquartile range (IQR): 11.2-16.7), and 10 were boys. Class B of the CDC classification system of AIDS was found in seven patients (44%), class C in 6 (37%), and class A in 3 Articles (19%), and the median number of previous ART regimens was [5][6] (Tables 1 and 2). None of the patients included had opportunistic or other infections during the study.…”

Section: Resultsmentioning

confidence: 99%

“…Interpretation of resistance tests in this context can be complex, particularly in the presence of expanding options for ARV drugs, and treatment decisions should be made with the support of pharmacists and clinicians who have expertise in the field (5).…”

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Genotype-guided antiretroviral regimens in children with multidrug-resistant HIV-1 infection

et al. 2016

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Background: Genotyping tests were developed to attenuate the impact of viral resistance. Information about the efficacy in genotype base antiretroviral therapy in children is rare and even more in low-and middle-income countries. Methods: Sixteen children with antiretroviral therapy (ART) failure and triple-class drug-resistant viruses were included in this study. Protease and retrotranscriptase genotypes were available for all patients. Switch of ART regimen was guided by genotyping data. The primary end point was virological suppression (<50 copies/ml) and immunological improvement after 48 wk of treatment with the new ART regimen. results: The median age of the patients was 14.5 y (interquartile range (IQR) 11-16.5). Median HIV-1 RNA viral load was 4.2 log 10 (IQR: 3.4-4.8). The primary end point was found in 11 children (69%), and 13 children (81%) had an HIV-1 RNA viral load <200 copies/ml. Median (IQR) for the baseline CD4 + cell count was 382 cells/μl (281-686 cells/μl), whereas after 48 wk of treatment with the new ART regimen, it was 640 cells/μl (361-936 cells/μl) (P < 0.001). conclusion: Darunavir/ritonavir, raltegravir, and etravirine were well tolerated in the present pediatric population. These drugs provide good options for children exposed to extensive ART. Regimens guided by genotyping data were effective for children who had ART failure and multidrug-resistant HIV-1 infection.i nfants and children who were infected perinatally are now surviving to adulthood with lifelong HIV infection and longterm exposure to combined antiretroviral therapy (ART) (1). Data from the United Kingdom Collaborative HIV Pediatric Study cohort demonstrated that over one-third of children had experienced virological treatment failure and were on a second or subsequent line of therapy at the time of their transition to adult care (2). In the pediatric setting, virological treatment failure occurs most frequently because of poor adherence to ART, and whenever viral replication is inefficiently controlled, virological treatment failure occurs more quickly, allowing the selection of HIV-1 quasispecies resistant to antiretroviral (ARV) drugs (3).Many innate and external factors have been associated with HIV drug resistance mutations in children, such as being infected perinatally, and extremely high viral load during the first steps of the infection, which can take longer to suppress than that in older children or adults, even when they are on fully active ART regimens (4).Interpretation of resistance tests in this context can be complex, particularly in the presence of expanding options for ARV drugs, and treatment decisions should be made with the support of pharmacists and clinicians who have expertise in the field (5).Currently, more than 20 different ARV drugs with six different classes of action have been approved for use in children or adolescents with HIV infection worldwide; most of them are used in Mexico (6).A good level of adherence is particularly difficult during adolescence, especially with a complex regimen ...

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Viral Load and Disease Progression in Infants Infected with Human Immunodeficiency Virus Type 1

Cited by 500 publications

References 21 publications

Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study

Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study

Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure

Genotype-guided antiretroviral regimens in children with multidrug-resistant HIV-1 infection

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