Vertical HIV Infection Research Articles

Systematic review of neuroimaging studies in vertically transmitted HIV positive children and adolescents

One of the most serious consequences of vertical HIV-infection is its impact on the central nervous system (CNS). Although much work has been done to elucidate the complex mechanism of HIV associated neurotoxicity, several questions remain unanswered. The purpose of this review is to summarise what is already known in the field of neuroimaging in vertically acquired HIV, addressing three aims and to highlight possible future directions in using neuroimaging and neurocognitive testing to understand the spectrum of neurocognitive disorders in HIV positve children. Here we aim to address several clinically relevant questions in pediatric neuroHIV, using the current evidence base by conducting a systematic review. We aim to investigate what is known about the relationship between cognitive impairment and central nervous system damage in HIV as seen in neuroimaging studies, and to search for any evidence in the current literature which suggests a spectrum of neuocognitive disorders in vertically infected HIV. Secondly, we aim to enquire whether children with a clinical diagnosis of encephalopathy are clearly distinguishable from HIV positive children without encephalopathy on neuroimaging and neurocognitive testing. Finally aim to investigate what is known about the effect on the CNS of antiretroviral therapy in paediatric HIV. Three separate databases were searched and two investigators systematically evaluated the titles, abstracts, and keywords associated with each individual article to determine those that may have met the inclusion and exclusion criteria. Following this process 11 studies were included in the review. Thus there was limited available data to address the 3 questions posed.

Clinicoepidemiologic Status of Mother-To-Child Infections

We conducted a nationwide survey of the present status of 10 representative mother-to-child infections in Japan. Congenital syphilis, vertical human T-cell leukemia virus type 1 infection, congenital rubella and vertical HIV infection, for which effective preventative strategies have been established, were rare. Cytomegalovirus was the most common congenital pathogen in Japan, although most infants with congenital cytomegalovirus infection may remain undiagnosed.

Abnormalities in body composition and nutritional status in HIV-infected children and adolescents on antiretroviral therapy

This cross-sectional study aimed to compare growth, nutritional status and body composition outcomes between a group of 94 HIV-infected children and adolescents on antiretroviral therapy (ART) and 364 healthy controls, and to evaluate their association with clinical and lifestyle variables within the HIV-infected group. When compared with the control group, HIV patients had higher risk of stunting (odds ratio [OR] 5.33, 95% confidence interval [CI]: 2.83-10.04) and thinness (OR 4.7, 95% CI: 2.44-9.06), higher waist-to-hip ratios (medians 0.89 versus 0.82 for boys and 0.90 versus 0.77 for girls, P < 0.001), and lower prevalence of overweight or obesity (OR 0.33, 95% CI: 0.14-0.78). Protease inhibitor usage was associated with thinness (OR 3.51, 95% CI 1.07-11.44) and lipoatrophy (OR 3.5, 95% CI 1.37-8.95). HIV-infected children on ART showed significant nutritional status and body composition abnormalities, consistent with the severity of vertical HIV infection and the consequences of prolonged ART.

Outcome of PMTCT services and factors affecting vertical transmission of HIV infection in Lagos, Nigeria

With the global focus on PMTCT as a means of reducing the burden of paediatric HIV infection and the scale up of PMTCT services in Nigeria, there is need for a review of the work already done to inform an effective programme. This is a retrospective analysis of the HIV DNA PCR results of 733 HIV exposed babies seen between February 2007 and February 2008 at six public hospitals in Lagos, Nigeria. Of the 733 HIV-exposed babies, 165 (22.5%) had positive HIV DNA PCR result (HIV infected vertically) while 568 (77.49%) had negative HIV DNA PCR result. Of the 165 babies with vertical HIV infection, 21 (12.7%) had caesarean delivery, 144 (87.3%) had vaginal delivery, 91 (55.2%) were breastfed, 74 (44.8%) had replacement feeding, 16 (9.7%) had mothers that had PMTCT services while 149 (90.3%) had mothers without the PMTCT services. While in the category of the 568 babies with negative HIV DNA PCR result, 204 (35.9%) had caesarean delivery and 364 (64.1%) were delivered vaginally, 99 (17.4%) were breastfed and 469 (86.6%) had replacement feeding, 410 (72.2%) had mothers who had PMTCT services and 158 (27.8%) babies’ mothers did not go through the PMTCT programme. More boys (391, 53%) than girls (342, 47%) were HIV-exposed but equal number were HIV infected (girls – 82, boys – 83) and same proportions were HIV negative (boys – 308, girls – 260). The modal age group among the exposed babies was 6–16 weeks. The average rate of vertical HIV transmission was 22.5%, but for babies whose mothers had PMTCT service the rate was 9.6%. Higher transmission rates were associated with vaginal delivery, breastfeeding and lack of PMTCT services to the mothers. The PMTCT service should therefore be strengthen and scale up to more centers.

Evaluation of the effectiveness and safety of chemoprophylaxis for vertical HIV transmission, by using the regimens of monotherapy and highly active antiretroviral therapy

The study including 69 pregnant women diagnosed as having HIV infection who received chemoprophylaxis for vertical HIV infection evaluated the effectiveness and safety of the regimens of monotherapy and highly active antiretroviral therapy (HAART) used during pregnancy. There was a significant reduction in the levels of HIV RNA and an increase in the CD4 lymphocyte count in the patients receiving both chemoprophylaxis regimens. The efficiency of HAART regimens to prevent vertical HIV transmission was significantly higher than that of monoprophylaxis. The use of antiretroviral drugs was safe as monotherapy and in the HAART regimens during pregnancy.

Pediatric HIV BioBank: A New Role of the Spanish HIV BioBank in Pediatric HIV Research

The vulnerability of children has long raised ethical concerns resulting in the lack of inclusion of children in research studies. This has impeded the development of relevant medical therapies specific for children. In response to these circumstances, international policies have begun to recognize the need to carry out research focused on children. Translational HIV infection research is highly dependent on many factors including the availability, quality, and traceability of samples and their associated data under a strict system of quality management. The primary objective of the Pediatric HIV BioBank is to contribute to the furthering of scientific knowledge about vertical HIV infection. To achieve this aim, the BioBank processes, stores, and provides distinct samples from HIV/AIDS children to research projects free of charge. Strict compliance to ethical norms is always guaranteed. At present the Pediatric HIV BioBank has 429 vials containing different sample types from 243 vertically HIV-infected children. The Pediatric HIV BioBank represents a novel approach to HIV research that might be of general interest not only for basic and clinical research teams working with HIV, but also for those groups trying to establish large networks focused on researching specific clinical problems. It also represents a model to stimulate cooperative research on specific clinical problems. The main objective of this article is to show the structure and function of the Pediatric HIV BioBank that allow it to efficiently provide samples to different research projects in Spain and in other countries.

AIDS among older children and adolescents in Southern Africa: projecting the time course and magnitude of the epidemic

An AIDS epidemic among older children and adolescents is clinically apparent in Southern Africa. We estimated the likely scale and time course of the epidemic in older survivors of vertical HIV infection. We modelled demographic, HIV prevalence, mother-to-child transmission and child survival data to project HIV burden among older children in two Southern African countries at different stages of severe HIV epidemics. Using measured survival data for children, we estimate that 64% of HIV-infected infants are fast progressors with median survival 0.64 years and 36% are slow progressors with median survival 16.0 years. We confirmed model validity by comparing model predictions to available epidemiological data. Without treatment, HIV prevalence among 10-year-olds in South Africa is expected to increase from 2.1% in 2008 to 3.3% in 2020, whereas in Zimbabwe, it will decrease from 3.2% in 2008 to 1.6% in 2020. Deaths among untreated slow progressors will increase in South Africa from 7000/year in 2008 to 23 000/year in 2030, and in Zimbabwe from 8000/year in 2008 to peak at 9700/year in 2014. Drugs to prevent mother-to-child transmission could reduce death rate in 2030 to 8700/year in South Africa and to 2800/year in Zimbabwe in 2014. A substantial epidemic of HIV/AIDS in older survivors of mother-to-child transmission is emerging in Southern Africa. The lack of direct observations of survival in slow progressors has resulted in failure to anticipate the magnitude of the epidemic and to adequately address the clinical needs of HIV-infected older children and adolescents. Better HIV diagnostic and care services for this age group are urgently required.

Effect of HIV vertical transmission on the ontogeny of T cell antigens involved in the regulation of humoral immune response.

HIV infection causes progressive impairment of humoral immunity, including defective specific antibody production. To evaluate whether vertical HIV infection interferes with the expression on CD4+ lymphocytes of developmentally regulated molecules, that play a crucial role in the generation of immunological memory (CD45 isoforms) and in attainment of antibody responses (CD40L), 22 HIV-infected children and 36 seroreverted children born to HIV+ mothers were studied. The percentage of CD40L+ PBMC after activation in vitro with phorbol myristate acetate (PMA) plus ionomycin was lower in HIV-infected children than in controls (P < 0.004). This correlated with the depletion of CD4+ lymphocytes (r = 0.75; P < 0.001). CD40L expression rose progressively with age (r = 0.36; P = 0.03) in seroreverted children, but not in HIV-infected children, suggesting that while in normal children in vivo antigen stimulation results in progressive attainment of CD40L expression (and thus to effective T-B cell cooperation), this process is largely defective in HIV-infected children, contributing to the genesis of humoral immune deficiency. The proportion of CD4+ cells bearing the CD45RO isoform was increased among HIV-infected infants during the first years of life. However, the percentage of CD4+ CD45RO+ peripheral blood mononuclear cells (PBMC) progressively increased with age in controls (r = 0.69; P = 0.03), but not in HIV-infected children, showing that while vertical transmission of HIV does not prevent CD45RO expression early in life, it is associated with a disturbance of the physiological process of antigen priming, contributing to poor immunological memory to T cell-dependent antigens.

Effects of vertical HIV infection on the persistence of anti-HBs after a schedule of three doses of recombinant hepatitis B vaccine

Anti-HBs persistence following HBV vaccination among HIV-positive children has never been systematically studied in central Brazil. An historical cohort study was performed aiming to evaluate persistence of anti-HBs in HIV-positive children in comparison with an HIV-negative child group. Fifty-eight HIV-positive and 116 HIV-negative individuals were enrolled. Birth weight, breast-feeding duration, and the time elapsed since the last hepatitis B vaccine doses were similar between the groups. Fourteen (24%) out of 58 HIV-positive participants were anti-HBs positive and 101 (87%) out of 116 were HIV-negative (p<0.001). Among anti-HBs-positive individuals, the geometric mean titres were 118 and 298 mIU/mL, respectively to HIV-positive and HIV-negative groups (p=0.04). These results disclose a worrying picture regarding the failure of standard HBV vaccination among Brazilian HIV-infected children.

Immune activation and normal levels of endogenous antivirals are seen in healthy adolescents born of HIV-infected mothers

Immunological analyses performed in healthy adolescents born of HIV-infected (seroreverters) or healthy mothers (healthy controls; HC) showed that immune activation and a skewing of postthymic differentiation are present in adolescent seroreverters. In-utero HIV exposure results in long-lasting imprinting on the immune system. Alternatively, an immune response naturally more prone to activation could prevent vertical infection. Endogenous antivirals (APOBEC, TRIM5alpha) were comparable in seroreverters and HC, and might not play a role in resistance to vertical HIV infection.

CD8+CD28- T cells in vertically HIV-infected children.

To evaluate whether vertical HIV infection interferes with the expression of CD28 on T lymphocytes, 25 HIV-infected children and 29 seroreverted children born to HIV+ mothers were studied. The percentage of CD28- cells among CD8+ T lymphocytes was higher in HIV-infected children than in controls (P < 0.001). In fact, in HIV-infected children, this percentage was elevated from the first year of life, while in healthy seroreverted children, the proportion of CD28- cells among CD8+ cells rose progressively with age (r = 0.49; P = 0.008). In HIV+ children, the CD8+ CD28-, but not CD8+ CD28+ cell proportion was significantly correlated with immunological markers of disease progression, such as CD4+ cell loss (r = -0.65; P < 0.001) and the level of in vitro spontaneous lymphocyte apoptosis (r = 0.53; P = 0.03).

Neuroprotective effects of early antiretrovirals in vertical HIV infection

We performed a retrospective study of a series of 58 of 189 vertically HIV-1 infected children who went on to develop progressive HIV-1-associated encephalopathy to assess real-life effects of early antiretroviral therapy on neurologic outcome. Our findings clearly indicate that antiretroviral therapy before the onset of neurologic symptoms delayed presentation of progressive HIV-1-associated encephalopathy, with an additional beneficial effect on survival.

Oral manifestations of pediatric vertical HIV infection.

To assess the prevalence and prognostic significance of the history of oral manifestations in children with human immunodeficiency virus infection (HIV), a cohort study of 73 children with vertical HIV infection was conducted. The study subjects were examined every 6 months for oral manifestations. The period prevalence of oral manifestations ranged from a low of 1% for submandibular enlargement and 3% for hairy leukoplakia to a high of 36% for xerostomia and 51% for cervical lymphadenopathy. The occurrence of oral manifestations did not change significantly over time from 1995 to 1998. Finally, the odds of occurrence of cervical lymphadenopathy, xerostomia, and oral candidiasis were greater among children in whom these manifestations had been diagnosed in the preceding 6-18 months than in children without prior diagnosis. Oral manifestations are significant clinical outcomes in pediatric vertical HIV infection, particularly for children diagnosed previously with an oral manifestation.

Thymus volume correlates with the progression of vertical HIV infection.

The thymus is the organ responsible for the maturation and selection of T lymphocytes and is thus pivotal in allowing the development of a functional immune system. Because in HIV infection cell-mediated immune responses are severely impaired, we studied the role of thymus in the control of the progression of HIV infection to AIDS. Thymic volume was analysed by magnetic resonance imaging in 31 vertically HIV-infected children. Plasma HIV viral load and phenotypic and functional cellular immunity-defining parameters were examined in the same patients. Thymic volume was not correlated with age or nutritional status; thymic volume was nevertheless correlated with CD4 T-lymphocyte counts and with the percentage and absolute number of CD45RA+CD62L+ (naive) T lymphocytes. In addition, the ability of peripheral blood mononuclear cells to proliferate upon tetanus stimulation was directly proportional to thymic volume. Finally, a negative correlation was detected between thymic volume and HIV viral load. Because low HIV plasma viraemia and preserved immune function are favourable prognostic indices in HIV disease, these data indicate that an immunological, thymic-dependent control of the progression of HIV infection might be possible, at least in vertically transmitted HIV infection.

Response to influenza virus vaccination in vertical HIV infection

OBJECTIVETo assess the antibody response to influenza vaccine of children vertically infected with HIV.DESIGNProspective study in HIV infected children vaccinated during the winter of 1994-5.SETTINGFamily HIV clinic at St Mary’s...

The immune system in vertical HIV infection: the immune response and disease progression.

The immune system in vertical HIV infection: the immune response and disease progression.

Long-term resistance to HIV infection in vertical HIV infection: cytokine production, HIV isolation, and HIV phenotype define long-term resistant hosts.

We analyzed immunologic (CD4 and CD8 slopes; interferon-gamma, interleukin-2, interleukin-10, and chemokines production; concentration of IgE; beta 2-microglobulin) and virologic (p24; HIV isolability and phenotype; plasma viremia) parameters in HIV vertically infected children > or = 8 years of age without disease progression or mild symptoms and an absolute CD4+ count > or = 500/microliter with CD4+ percentage > or = 25%. The results were compared to those of two control groups: (1) slow progressors, children > or = 8 years of age with moderate symptomatology and/or moderate CD4 depletion, and (2) progressors, children > or = 8 years of age with severe clinical disease and/or severe CD4 depletion. Pediatric long-term resistant hosts were characterized by higher production of interleukin-2 and interferon-gamma and lower production of interleukin-10, normal concentration of IgE, HIV isolates with a non-syncytium-inducing phenotype, and lower plasma viremia. This condition was not associated with the concentration of beta 2-microglobulin, p24, and chemokines, or with HIV isolability. The IL-10/IL-2 ratio best correlated with both CD4 counts and disease progression. Thus, vertically infected children showing resistance to disease progression are immunologically and virologically distinct from those in whom progressive HIV infection is observed.

Increased serum levels of soluble tumor necrosis factor receptors (sTNF-Rs) in children and adolescents with vertically and horizontally transmitted HIV infection.

Two different receptors exist for tumor necrosis factor-alpha (TNF-alpha), designated as p55 (TNF-RI) and p75 (TNF-RII). Soluble (= s) forms of TNF-Rs are secreted after proteolytic cleavage and block the effects of TNF-alpha. sTNF-RI, sTNF-RII and the soluble interleukin 2 receptor (sIL-2R) were determined by ELISA in serum samples of HIV-infected children and adolescents. Twelve children with vertical HIV infection (mean age +/- SD, 5.9 +/- 3.8 years) and 17 horizontally infected patients (16.1 +/- 7.3 years) were classified according to the revised CDC criteria. Twenty healthy control persons (6.4 +/- 5.8 years) showed the following receptor concentrations (median): sTNF-RI 888 pg/ml, sTNF-RII 1,741 pg/ml, sIL-2R 94 pM. Compared to controls, horizontally HIV-infected patients had significantly (Mann-Whitney U test) higher levels for sTNF-RI (median 1,192 pg/ml), sTNF-RII (3,481 pg/ml) and sIL-2R (128 pM). For vertically infected children only sTNF-RII (2,944 pg/ml) was significantly elevated compared to controls. There were no differences in soluble receptor levels between vertical or horizontal transmission. Surprisingly, no significant differences for sTNF-RI, sTNF-RII and sIL-2R occurred when 19 patients in stage CDC I were compared to ten patients in stages II or III. The clearly elevated sTNF-RII levels in patients with horizontal and vertical HIV infection indicate the activation of the monocyte/macrophage system in both groups.

DNA Polymerase Chain Reaction for the Diagnosis of Vertical HIV Infection

The prevalence of pediatric human immunodeficiency virus type 1 (HIV) infection has increased rapidly through the vertical transmission of HIV from infected women to their infants. In 1995, a cumulative total of approximately 20 000 children in the United States and 1.5 million children worldwide were infected with HIV. 1,2 In the United States, 0.17% of all childbearing women are HIV-seropositive, and approximately 7000 infants are born to HIV-infected women each year. Recently, the perinatal administration of zidovudine was shown to substantially reduce vertical HIV transmission. 3,4 In an effort to further reduce vertical HIV transmission, perinatal trials of newer antiretroviral agents alone and in combination are under way. Major efforts must continue to be made to offer HIV testing to all pregnant women and to monitor the infection status of their infants. Infants infected with HIV must be diagnosed as rapidly as possible to ensure the early institution of

DNA polymerase chain reaction for the diagnosis of vertical HIV infection

DNA polymerase chain reaction for the diagnosis of vertical HIV infection