Mary E. Paul

Continuous improvement in the immune system of HIV-infected children on prolonged antiretroviral therapy

Background: The goal of HAART is to promote reconstitution of CD4+ T cells and other immune responses. We evaluated the extent and the kinetics of immune reconstitution in HIV-infected children over 144 weeks of successful HAART. Methods: Thirty-seven children receiving their first HAART regimen had plasma HIV RNA; T cells and subpopulations; T-cell rearrangement excision circles (TREC) DNA; candida, HIVCD4 and HIVCD8 enzyme-linked immunospot measured at regular intervals. Results: Plasma HIV RNA became undetectable in 81% of patients at 24 weeks and remained undetectable in 77% at 144 weeks. In contrast, CD4+% continuously increased. Distribution of T-cell subpopulations changed rapidly during the first 48 weeks of HAART and more slowly thereafter. At 144 weeks, total, naive and activated CD4+% and naive CD8+% of HIV-infected children were not significantly different from those of healthy age-matched controls, whereas total and activated CD8+% remained elevated. CD4+ and CD8+ TREC content increased only during the first 48 weeks of HAART. They positively correlated with each other and with total CD4+%, naive CD4+% and naive CD8+%. Candida and HIVCD4 enzyme-linked immunospot increased over time reaching peak values at 48 weeks and 144 weeks, respectively. HIVCD8 enzyme-linked immunospot decreased in magnitude over 144 weeks of HAART but retained its breadth. Baseline CD4+% positively correlated with CD4+% and with functional immune reconstitution at week 144, whereas baseline TREC correlated with TREC at week 144. Conclusion: HIV-infected children acquired normal distribution of CD4+ T cells and other subpopulations and recovered CD4-mediated HIV immunity after 144 weeks of HAART.

THE CHILD WHO HAS RECURRENT INFECTION

Every pediatrician is faced with the fact that some children have more infections than others. A parents need for an explanation regarding the frequency of infection increases with increasing effect of infections on quality of life for both the child and the parent. Sometimes, type or severity of infection, family history, or physical examination provides a clue that the immune system is not functioning poperly. This article discusses the infants immune system, the expected numbers of infection in childhood, the factors influencing the number of infections, the differential diagnosis for recurrent infection, and the diagnosis of immune deficiency.

Pharmacokinetics of Rilpivirine in HIV-Infected Pregnant Women.

Background:Rilpivirine pharmacokinetics is defined by its absorption, distribution, metabolism, and excretion. Pregnancy can affect these factors by changes in cardiac output, protein binding, volume of distribution, and cytochrome P450 (CYP) 3A4 activity. Rilpivirine is metabolized by CYP3A4. The impact of pregnancy on rilpivirine pharmacokinetics is largely unknown. Methods:International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is a multicenter, nonblinded, prospective study evaluating antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving rilpivirine 25 mg once daily as part of their combination antiretrovirals for clinical care. Thirty-two women were enrolled in this study. Intensive pharmacokinetic sampling was performed at steady state during the second trimester, the third trimester, and postpartum. Maternal and umbilical cord blood samples were obtained at delivery. Plasma rilpivirine concentration was measured using liquid chromatography–mass spectrometry; lower limit of quantitation was 10 ng/mL. Results:Median (range) AUC0–24 were 1969 (867–4987, n = 15), 1669 (556–4312, n = 28), and 2387 (188–6736, n = 28) ng·h/mL in the second trimester, the third trimester, and postpartum, respectively (P < 0.05 for either trimester vs postpartum). Median (range) C24 were 63 (37–225, n = 17), 56 (<10–181, n = 30), and 81 (<10–299, n = 28) ng/mL (P < 0.05 for either trimester vs postpartum). High variability in pharmacokinetic parameters was observed between subjects. Median (range) cord blood/maternal concentration ratio was 0.55 (0.3–0.8, n = 21). Delivery HIV-1 RNA was ⩽50 copies per milliliter in 70% and ⩽400 copies per milliliter in 90% of women. Cmin were significantly lower at 15 visits with detectable HIV-1 RNA compared with 61 visits with undetectable HIV-1 RNA, 29 (<10–93) vs 63 (15–200) ng/mL (P = 0.0001). Cmin was below the protein binding–adjusted EC90 concentration (12.2 ng/mL) at 4 visits in 3 of 31 women (10%). Conclusions:Rilpivirine exposure is lower during pregnancy compared with postpartum and highly variable. Ninety percent of women had minimum concentrations above the protein binding–adjusted EC90 for rilpivirine.

Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome

Abstract Although encouraged by the slow decline in the number of patients living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), the world waits with growing expectation that a cure will be discovered that will free it from HIV infection and AIDS. What is required to accomplish this difficult goal is the two-part intention to (i) rid the body of HIV reservoirs and (ii) develop a potential preventive vaccine. Multimodel approaches will almost certainly be necessary to eliminate this retrovirus from humans. Assuming that this can be accomplished, there is growing literature on the harmful effects of some agents used to treat HIV/AIDS. In addition to being compromised by HIV, organs and tissue systems may be further damaged by side effects of treatment. For the most part, however, antiretroviral therapy (ART) has been lifesaving and permits a reasonable quality of life for many years. But the strong pulse of scientific discovery that has been realized in the recent past gives great hope to those already infected with HIV and to those who yearn for a preventive vaccine to protect themselves.