Human Immunodeficiency Virus Infection In Infants Research Articles

Management of HIV Infection in Infants and Children

This is a well-written book. The chapter sequence is very logically organized. The editors have taken special care to arrange the book in a fashion that provides a good understanding of human immunodeficiency virus (HIV) infection. A significant portion of the book deals with the treatment of infants and children with HIV. However, before the treatment issues are dealt with, the first few chapters deal with understanding of the epidemiology, immunology, pathology, and diagnosis of HIV infection. These initial chapters are the major strength of this book. Chapters 4 through 6 by themselves are very useful in understanding HIV infection in children. In addition, the final three chapters of this book deal with important issues of HIV infection that are often neglected in medical texts. They address significant and practical societal issues of pediatric HIV infection. The chapters titled Immunodeficiency Virus: The Virus and Its Pathogenicity, Transmission of Human

3 Human immunodeficiency virus infection in pregnancy

Human immunodeficiency virus (HIV) infection in women is an increasing problem. World wide, at least 25% of all infections occur in adolescent or adult women, most of whom are of child-bearing age. The commonest modes of acquisition of HIV infection are sexual contact with an HIV-infected male and sharing needles during injecting drug use. Vertical transmission is the major route of HIV infection in infants and children and can occur in utero, intrapartum, through exposure to infected blood or secretions, or post partum, via breast milk. HIV infection has not been demonstrated to affect fertility, or to influence the outcome of pregnancy unless there is evidence of significant immune dysfunction, with CD4 counts below 400/mm3. Though data are limited, pregnancy does not appear to affect the course of HIV infection. Low CD4 counts predispose women to the opportunistic infectious complications of HIV. Pathogens include Candida sp., Mycobacterium tuberculosis, Pneumocystis carinii, Toxoplasma gondii, Cryptococcus neoformans and Cryptosporidium. These pathogens require early recognition and diagnosis if optimal treatment and outcome are to be attained. Treatment with zidovudine and prophylaxis against Pneumocystis carinii are appropriate when CD4 counts are less than 200/mm3, though the safety of zidovudine in early pregnancy is not known. Similarly it is not known whether zidovudine treatment of the mother prevents transmission of HIV infection to her baby. Caesarean section does not prevent peripartum transmission of HIV and should be undertaken only for other appropriate indications. The utility of antenatal screening for HIV depends upon the seroprevalence in the population. Such programmes must be supported by comprehensive clinical care as well as sensitive and non-judgemental counselling.

A human milk factor inhibits binding of human immunodeficiency virus to the CD4 receptor.

Perinatal transmission of human immunodeficiency virus (HIV) from infected mothers to their children occurs at rates reported as 20-50%. The role of breast feeding in perinatal transmission of viral infections has not been well established. We studied 34 milk and colostral samples obtained from HIV-seropositive and HIV-seronegative women to determine if they contained anti-HIV activity. We found that all the samples contained a factor that inhibited the binding of HIV epitope-specific MAb to recombinant CD4 receptor molecules. The titers of inhibitory activity ranged from 1:200 to 1:10,000 and did not differ between HIV-seropositive and HIV-seronegative mothers. This milk factor also inhibited the binding of gp120 to CD4. Neither human sera nor bovine milk exhibited appreciable inhibitory activity. Fractionation of human milk indicated that the inhibitory activity was confined to the macromolecular fraction; little activity was found in isolated milk lipids or oligosaccharides. Chromatographic procedures indicated that the active macromolecule has an isoelectric point of 9.3-9.6. The active material did not bind to concanavalin A; however, the activity was partially destroyed by chemical and enzymatic treatments that removed sulfated residues. The active material may thus be a sulfated protein, glycoprotein, mucin, or glycosaminoglycan that inhibits the binding of CD4 to HIV envelope glycoproteins. The role of this factor in the natural history of HIV infection in infants and children should be the subject of additional investigations.

Clinical Utility of HIV-IgA Immunoblot Assay in the Early Diagnosis of Perinatal HIV Infection

To ascertain the sensitivity, specificity, predictive value, and clinical use of a human immunodeficiency virus (HIV)-IgA immunoblot assay for diagnosing perinatal HIV infection in infants tested at birth to 1 month, 3 months, and 6 months of age. Prospective, longitudinal cohort study of children born to HIV-infected and noninfected women. The HIV-IgA immunoblot assays were performed at birth to 1 month, 3 months, and 6 months of age and compared with the Centers for Disease Control's classification system of HIV infection in the children. Children were followed up for at least 15 months to ensure accuracy of infection status. Municipal hospital in central Brooklyn, NY, where the prevalence of HIV infection is high. Serum samples from 58 children, 22 with documented HIV infection, 18 noninfected children born to seropositive women, and 18 children born to noninfected women, were studied. Diagnosis of HIV infection using the Centers for Disease Control's classification scheme was compared with diagnosis using the HIV-IgA immunoblot assay for children 6 months of age or younger. The HIV-IgA immunoblot assay yielded negative results at 3 and 6 months of age for all 18 infants born to seronegative women; for the 18 seroreverting, noninfected children born to infected women, the assay yielded negative results at 1 month, 3 months, and 6 months of age. The positive predictive value of the assay was 100%--no false-positive results were identified in the 88 serum samples obtained from noninfected infants. For the HIV-infected children, sensitivity was a function of age: one (5.9%) of 17 infants had an assay that yielded positive results at birth to 1 month of age, 13 (62%) of 21 infants had assays that yielded positive results at 3 months of age, and 17 (77%) of 22 infants had assays that yielded positive results at 6 months of age. The presence or absence of symptoms did not affect the sensitivity. The HIV-IgA immunoblot assay can detect a significant proportion of infected children during an early asymptomatic period of their life. This relatively inexpensive, easily standardized assay may allow for institution of therapy before the onset of clinical symptoms.

Repeated polymerase chain reaction complementary to other conventional methods for early detection of HIV infection in infants born to HIV-infected mothers

The efficacy of a polymerase chain reaction (PCR) method for early detection of human immunodeficiency virus (HIV) in infants at risk for HIV infection was assessed. The PCR method was added to the routine laboratory test programme in these patients in 1988. PCR was performed in a total of 26 children at risk (age range 2 days to 58 months), including 17 infants born to HIV-infected mothers, who were followed up clinically from the time of birth for a mean period of 23 months (range 6 to 54) in a prospective study. Twelve children were PCR-positive. Eight had AIDS, ARC or symptoms suggestive of HIV infection. All these patients had at least one culture positive for HIV (6/8) and/or one positive serum p24-antigen test (5/8). One child was repeatedly PCR positive, but asymptomatic as well as virus- and antigen-negative. Three asymptomatic children with a single positive PCR result were PCR negative in subsequent tests. Fourteen children with negative PCR did not show clinical or immunological signs suggestive of HIV infection. Their cultures for HIV and antigen-p24 assays were negative. It is concluded that in addition to clinical and immunological parameters PCR is a useful technique for diagnosis of HIV infection in infants born to HIV-infected mothers. However, in case of negative HIV cultures and/or serum p24-antigen tests, single positive PCR results in asymptomatic patients must be interpreted with caution and should be confirmed by repeated tests.

Hypogammaglobulinemia in uremic infants receiving peritoneal dialysis

7. Borkowsky W, Krasinski K, Paul D~ et al. Human immunodeficiency virus infections in infants negative for anti-H1V by enzyme-linked immunoassay. Lancet 1987;1:1168-71. 8. Consortium for Retrovirus Serology Standardization. Serologic diagnosis of human immunodeficiency virus infection by Western blot testing. JAMA 1988;260:674-8. 9. Centers for Disease Control. Classification system for human immunodeficiency virus (HIV) infection in children under 13 years of age. MMWR 1987;36:91-6. l 0. Johnson J, Davis E, Sbinaberry R, Nair P. Serologic responses to HIV infection in infants. Presented at the Fifth International Conference on AIDS, Montreal, Quebec, Canada, June 4-9, 1989. 11. Martin K, Katz B, Miller G. AIDS and antibodies to human immunodeficiency virus in children and their families. J Infect Dis 1987;155:54-9. 12. Epstein L, Boucher C, Morrison S, et al. Persistent human immunodeficiency virus type 1 antigenemia in children correlates with disease progression. Pediatrics 1988;82:919-24. 13. Ou C-Y, Kwok S, Mitchell SW, et al. DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science 1988;7:825-35. 14. Amadori A, De Rossi A, Gaguinto C, et al. In vitro production of HIV-specific antibody in children at risk of AIDS. Lancet 1988;1:852-4.

Treatment of human immunodeficiency virus-infected infants and young children with dideoxynucleosides

The safety and activity of several antiretroviral agents are being evaluated for treatment of acquired immunodeficiency syndrome (AIDS) in infants and children. Intermittent oral and intravenous regimens and continuous intravenous infusion of the dideoxynucleoside, 3′-azido-3′-deoxythymidine (zidovudine, AZT), have been shown to be beneficial in improving neurodevelopmental function and growth velocity in pediatric patients with AIDS. AZT, however, is limited by the associated development of neutropenia and anemia, which frequently necessitates transfusions. Another dideoxynucleoside, 2′,3′-dideoxycytidine (ddC), also shows theoretical promise in the treatment of the pediatric AIDS population. This agent is not associated with the hematologic toxicity induced by AZT but does produce a painful sensory peripheral neuropathy. Sequential therapy with AZT and ddC may limit the toxic effects associated with the use of these drugs individually. Dideoxyinosine and soluble recombinant CD4 are two newer antiretroviral agents that are under investigation for the management of AIDS in infants and children. The activity of recombinant CD4 in preventing the transplacental transmission of human immunodeficiency virus is also being evaluated.

Early diagnosis of HIV infection in infants by detection of IgA HIV antibodies

With the aim of achieving earlier diagnosis of human, immunodeficiency virus (HIV) infection in infants, IgA and IgM HIV antibodies in serum samples from babies born to seropositive mothers were assayed by immunoblot and enzyme-linked immunosorbent assay after removal of IgG with recombinant protein G. 64 samples were from 38 HIV-infected babies with Centers for Disease Control classifications of P1 or P2. Among these infected children IgA HIV antibodies were present in all 23 samples from those older than 12 months, in 12 of 18 samples from babies aged 6-12 months, in 5 of 10 samples from babies aged 3-5 months, and in 2 of 13 from babies under 3 months old. The 6 IgA-negative samples from infants over 6 months were all from infants with severe AIDS and/or hypogammaglobulinaemia. IgA HIV antibodies were present in twice as many samples as IgM HIV antibodies (66% vs 33%). No IgM or IgA HIV antibodies were detected in infants who subsequently seroreverted or in infants born to seronegative mothers. The correlation of the serological results with clinical information on each child suggests that detection of IgA HIV antibodies is an effective method for early diagnosis of HIV-infected infants without signs of infection.

Human immunodeficiency virus infection in childhood

Acquired immunodeficiency syndrome is associated with considerable morbidity in infants and children. It is caused by human immunodeficiency virus (HIV) which can be transmitted vertically from mother to infant early in pregnancy. Transmission might also occur via breast milk. Although the exact transmission rate of HIV from mother to infant is not known, HIV can become a major threat to child survival. This threat is already present in Africa where high seroprevalences have been reported among infants and young children. Transmission via blood products is decreasing due to reliable methods of screening donors for HIV antibody. Where these tests are not available, parenteral transmission will increase the incidence of HIV infection. The clinical picture of HIV infection in children presents with failure to thrive, pulmonary interstitial pneumonitis, hepatosplenomegaly and recurrent bacterial infections. These are common manifestations of diseases prevalent in children in Africa where malnutrition and recurrent parasitic infections already cause immunosuppression. Recognition of the syndrome is therefore difficult. There is no available cure for HIV infection. Supportive treatment and relief of pain and suffering are the only means of management at present. Prevention of spread of the illness to infants and young children is therefore of paramount importance.

Fetal AIDS Syndrome Score

To objectively evaluate the fetal acquired immunodeficiency syndrome, we have developed a scoring system based on the presence of the characteristic features that we have previously reported. Using this scoring system, 37 children seropositive for the human immunodeficiency virus were classified into three groups: dysmorphologically severely affected (12 children); moderately affected (15 children); and mildly affected (ten children). There was a statistically significant correlation between the severity of the dysmorphic features and both the presence of opportunistic infections within the first year of life and the age at onset of symptoms associated with immune dysfunction, with the more severely stigmatized children manifesting symptoms at a younger age. There was no correlation, however, between severity of the dysmorphic features and presence of opportunistic infections at the time of our examination. We conclude that this scoring system may be useful in presymptomatic identification of severely dysmorphic human immunodeficiency virus-infected infants.