A review of statistical methods for estimating the risk of vertical human immunodeficiency virus transmission.
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BACKGROUND: Estimation of the risk of vertical transmission of human immunodeficiency virus (HIV) has been complicated by the lack of a reliable diagnostic test for paediatric HIV infection. METHODS: A literature search was conducted to identify all statistical methods that have been used to estimate HIV vertical transmission risk. Although the focus of this article is the analysis of birth cohort studies, ad hoc studies are also reviewed. CONCLUSIONS: The standard method for estimating HIV vertical transmission risk is biased and inefficient. Various alternative analytical approaches have been proposed but all involve simplifying assumptions and some are difficult to implement. However, early diagnosis/exclusion of infection is now possible because of improvements in polymerase chain reaction technology and complex estimation methods should no longer be required. The best way to analyse studies conducted in breastfeeding populations is still unclear and deserves attention in view of the many intervention studies being planned or conducted in developing countries. (+info)
Demographic, clinical and social factors associated with human immunodeficiency virus infection and other sexually transmitted diseases in a cohort of women from the United Kingdom and Ireland. MRC Collaborative Study of women with HIV.
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BACKGROUND: Clinical experience suggests many women with HIV infection have experienced no other sexually transmitted diseases (STD). Our objective was to test the hypothesis that a substantial proportion of women with HIV infection in the United Kingdom and Ireland have experienced no other diagnosed STD and to describe the demographic, clinical and social factors associated with the occurrence of other STD in a cohort of HIV infected women. METHOD: Analysis of cross-sectional baseline data from a prospective study of 505 women with diagnosed HIV infection. The setting was 15 HIV treatment centres in the United Kingdom and Ireland. The main outcome measures were occurrence of other STD diagnosed for the first time before and after HIV diagnosis. Data were obtained from interview with women and clinic notes. We particularly focused on occurrence of gonorrhoea, chlamydia and trichomoniasis after HIV diagnosis, as these are the STD most likely to reflect recent unprotected sexual intercourse. RESULTS: The women were mainly infected via heterosexual sex (n = 304), and injection drug use (n = 174). 151 were black Africans. A total of 250 (49.5%) women reported never having been diagnosed with an STD apart from HIV, 255 (50.5%) women had ever experienced an STD besides HIV, including 109 (21.6%) who had their first other STD diagnosed after HIV. Twenty-five (5%) women reported having had chlamydia, gonorrhoea or trichomoniasis diagnosed for the first time after HIV diagnosis, possibly reflecting unprotected sexual intercourse since HIV diagnosis. In all 301 (60%) women reported having had sex with a man in the 6 months prior to entry to the study. Of these, 168 (58%) reported using condoms 'always', 66(23%) 'sometimes' and 56 (19%) 'never'. CONCLUSIONS: Half the women in this study reported having never experienced any other diagnosed STD besides HIV. However, after HIV diagnosis most women remain sexually active and at least 5% had an STD diagnosed which reflect unprotected sexual intercourse. (+info)
Pregnancy, body weight and human immunodeficiency virus infection in African women: a prospective cohort study in Kigali (Rwanda), 1992-1994. Pregnancy and HIV Study Group (EGE).
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OBJECTIVE: To study the relationship between human immunodeficiency virus (HIV) infection and body weight in African women during and after pregnancy. METHODS: A prospective cohort study was initiated at the Centre Hospitalier de Kigali in July 1992. Every woman seen at the antenatal clinic and with a gestational age of <28 weeks was offered HIV-1 antibody testing. Comparable numbers of HIV-infected (HIV+) and uninfected (HIV-) women were recruited. At inclusion, socio-demographic characteristics and self-reported pre-pregnancy weight were recorded; height and weight were measured. Each woman enrolled had a monthly follow-up until 9 months after delivery, with a clinical examination including weighing. Three anthropometric indices were used to answer the study objectives: weight, body mass index (BMI), and pregnancy balance. RESULTS: As of April 1994, 101 HIV+ and 106 HIV- women were followed until 5 months after delivery. Weight and BMI during pregnancy were lower in HIV+ women than in HIV- women. After delivery, weight and BMI gains were significantly lower in HIV+ women. Until 5 months after delivery, the mean weight variation was -2.2 kg (standard deviation [SD] = 5.9 kg) in HIV+ women and +0.2 kg (SD = 6.6 kg) in HIV- women (P = 0.007) in comparison to pre-pregnancy weight. Comparisons of the slopes of the weight curves did not show statistical differences throughout the pregnancy, but it did during the post-partum period (P = 0.02). CONCLUSIONS: Our study suggests that HIV infection could impair nutritional status in pregnant women, especially during the post-partum period. Family planning and maternal and child health services including HIV testing and counselling, should consider a nutritional assessment and intervention programme targeted to HIV+ pregnant women. (+info)
Human immunodeficiency virus antibody testing by enzyme-linked fluorescent and western blot assays using serum, gingival-crevicular transudate, and urine samples.
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The aim of the present study was to evaluate the possible utilization of saliva and urine as alternative samples to serum for the diagnosis of human immunodeficiency virus (HIV) infection. A total of 302 individuals participated in the study: 187 HIV-infected individuals (106 had Centers for Disease Control and Prevention [CDC] stage II infection, 19 had CDC stage III infection, and 62 had CDC stage IV infection) and 115 noninfected persons (46 of the noninfected persons were blood donors and 69 belonged to a group at high risk of HIV infection). Paired saliva and urine samples were taken from each of the participants in the study. The presence of HIV-specific antibodies was detected by an enzyme-linked fluorescent assay (ELFA), and the result was confirmed by Western blot analysis (WB). The ELFA with saliva gave maximum sensitivity and specificity values, while ELFA had lower sensitivity (95.2%) and specificity (97. 4%) values for detection of HIV antibody in urine samples. WB with all saliva samples fulfilled the World Health Organization criterion for positivity, while only 96.8% of the urine samples were confirmed to be positive by WB. Among the four reactivity patterns found by WB of these alternative samples, the most frequent included bands against three groups of HIV structural proteins (was ENV, POL, and GAG). The reactivity bands most frequently observed were those for the proteins gp160 and gp120. The least common reactivity band was the band for protein p17. The detection of HIV antibodies in saliva samples by means of ELFA with the possibility of later confirmation by WB makes saliva an alternative to serum for possible use in the diagnosis of infection. In contrast, HIV antibody detection in urine samples by the same methodology (ELFA) could be taken into consideration for use in epidemiological studies. (+info)
Viral burden and disease progression in rhesus monkeys infected with chimeric simian-human immunodeficiency viruses.
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To determine the role of viral burden in simian-human immunodeficiency virus (SHIV)-induced disease, cellular provirus and plasma viral RNA levels were measured after inoculation of rhesus monkeys with four different SHIVs. These SHIVs included SHIV-HXBc2 and SHIV-89.6, constructed with env, tat, rev, and vpu derived from either cell line-passaged or primary patient isolates of human immunodeficiency virus type 1; the viral quasispecies SHIV-89.6P derived after in vivo passage of SHIV-89.6; and a molecular clone, SHIV-KB9, derived from SHIV-89.6P. SHIV-HXBc2 and SHIV-89.6 are nonpathogenic in rhesus monkeys; SHIV-89.6P and SHIV-KB9 cause rapid CD4(+) T cell depletion and an immunodeficiency syndrome. Relative SHIV provirus levels were highest during primary infection in monkeys infected with SHIV-89.6P, the virus that caused the most rapid and dramatic CD4(+) T cell depletion. However, by 10 weeks postinoculation, provirus levels were similar in monkeys infected with the pathogenic and nonpathogenic chimeric viruses. The virus infections that resulted in the highest peak and chronic viral RNA levels were the pathogenic viruses SHIV-89.6P and SHIV-KB9. SHIV-89. 6P uniformly caused rapid and profound CD4(+) T cell depletion and immunodeficiency. Infection with the SHIV-KB9 resulted in very low CD4(+) T cell counts without seroconversion in some monkeys and a substantial but less profound CD4(+) T cell depletion and rapid seroconversion in others. Surprisingly, the level of plasma viremia did not differ between SHIV-KB9-infected animals exhibiting these contrasting outcomes, suggesting that host factors may play an important role in AIDS virus pathogenesis. (+info)
Conformational aspects of HIV-1 integrase inhibition by a peptide derived from the enzyme central domain and by antibodies raised against this peptide.
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Monospecific antibodies were raised against a synthetic peptide K159 (SQGVVESMNKELKKIIGQVRDQAEHLKTA) reproducing the segment 147-175 of HIV-1 integrase (IN). Synthesis of substituted and truncated analogs of K159 led us to identify the functional epitope reacting with antibodies within the C-terminal portion 163-175 of K159. Conformational studies combining secondary structure predictions, CD and NMR spectroscopy together with ELISA assays, showed that the greater is the propensity of the epitope for helix formation the higher is the recognition by anti-K159. Both the antibodies and the antigenic peptide K159 exhibited inhibitory activities against IN. In contrast, neither P159, a Pro-containing analog of K159 that presents a kink around proline but with intact epitope conformation, nor the truncated analogs encompassing the epitope, were inhibitors of IN. While the activity of antibodies is restricted to recognition of the sole epitope portion, that of the antigenic K159 likely requires interactions of the peptide with the whole 147-175 segment in the protein [Sourgen F., Maroun, R.G., Frere, V., Bouziane, A., Auclair, C., Troalen, F. & Fermandjian, S. (1996) Eur. J. Biochem. 240, 765-773]. Actually, of all tested peptides only K159 was found to fulfill condition of minimal number of helical heptads to achieve the formation of a stable coiled-coil structure with the IN 147-175 segment. The binding of antibodies and of the antigenic peptide to this segment of IN hampers the binding of IN to its DNA substrates in filter-binding assays. This appears to be the main effect leading to inhibition of integration. Quantitative analysis of filter-binding assay curves indicates that two antibody molecules react with IN implying that the enzyme is dimeric within these experimental conditions. Together, present data provide an insight into the structure-function relationship for the 147-175 peptide domain of the enzyme. They also strongly suggest that the functional enzyme is dimeric. Results could help to assess models for binding of peptide fragments to IN and to develop stronger inhibitors. Moreover, K159 antibodies when expressed in vivo might exhibit useful inhibitory properties. (+info)
Infectious human immunodeficiency virus can rapidly penetrate a tight human epithelial barrier by transcytosis in a process impaired by mucosal immunoglobulins.
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Mucosal surfaces are the main natural site of entry into the body for human immunodeficiency virus (HIV). Herein, an alternative mechanism for virus spread is described. The mechanism, which involves transcytosis of endosome-internalized HIV-particles, was generated by contact of HIV-infected cells with the apical surface of an epithelial cell line. Transcytosed viruses rapidly (in 20-30 min) access the serosal side of the epithelial barrier without infecting the epithelium itself. In turn, transcytosed HIV could infect host submucosal mononucleated target cells, and thus the infection could spread. An investigation was done to determine whether mucosal antibodies could block HIV transcytosis. Both secretory IgA (S-IgA) and IgG that were purified from colostrum from HIV-seropositive women impaired HIV transcytosis, irrespective of the level of the recombinant HIV envelope anti-gp160-specific activities in an ELISA. However, specific S-IgAs were more efficient than IgG. Therefore, mucosal-specific S-IgA to HIV-1 could be relevant to reducing infectivity of HIV-1 in corporeal fluids. (+info)
Mucosal immune system of the human genital tract.
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In contrast to the pronounced dominance of secretory IgA over other immunoglobulin isotypes in human saliva, tears, milk, and gastrointestinal fluids, secretions of both female and male genital tracts contain more IgG than secretory IgA. Both IgG and IgA are derived, to a variable degree, from the systemic immunoglobulin pool as well as from local synthesis. The origin of IgG- and IgA-plasma cell precursors destined for the genital tract is unknown, but indirect evidence suggests that mucosal inductive sites localized in the rectum, small intestine, and especially in the nasal cavity contribute such precursors to the female genital tract. Several studies indicated that intranasal immunization of various species, including humans, was efficient at inducing antigen-specific antibody responses in the female genital tract; however, whether this route is also effective in males has not been explored. (+info)