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Gonzague Jourdain,1–3 Nicole Ngo-Giang-Huong,1–3 Woottichai Khamduang21Unit 174-PHPT, Institut de recherche pour le développement (IRD), Marseille, France; 2Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; 3Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA, USAAbstract: There is currently no cure for hepatitis B chronic infections. Because new hepatitis B infections result mainly from perinatal transmission, preventing mother-to-child transmission is essential to reach by 2030 the goal of hepatitis B elimination set by the World Health Organization. The universal administration of hepatitis B vaccine to all infants, regardless of maternal status, starting with the birth dose, is the cornerstone of the strategy for elimination. Additional interventions, such as hepatitis B immune globulin administered to newborns and antiviral prophylaxis administered to hepatitis B infected pregnant women, may contribute to reaching the goal earlier. Hepatitis B immune globulin may remain out for reach of many pregnant women in low- and middle-income countries due to cost and logistic issues, but antivirals are cheap and do not require a cold chain for distribution. However, it has been observed that some viruses harbor mutations associated with escape from vaccine-elicited antibodies following immunization or administration of hepatitis B immune globulin. Also, resistance associated mutations have been described for several drugs used for treatment of hepatitis B infected patients as well as for the prevention of mother-to-child transmission. Whether these mutations have the potential to compromise the prevention of mother-to-child transmission or future treatment of the mother is a question of importance. We propose a review of important recent studies assessing tenofovir disoproxil fumarate for the prevention of mother-to-child transmission, and provides detailed information on the mutations possibly relevant in this setting.Keywords: hepatitis B, mother-to-child transmission, prevention, antiviral, resistance

We analyzed the characteristics of the envelope genes of human immunodeficiency virus type 1 in 17 mother-infant pairs infected with variants of the CRF01_AE clade. A total of 353 sequences covering almost the entire glycoprotein (gp) 120 region were available for analysis. We found that, even if the virus population in the mother was complex, only viruses of a restricted subset were transmitted to her infant, independently of whether transmission occurred in utero or during the intrapartum period. We did not find that shorter gp120 regions or fewer potential N-glycosylation sites (PNGS) were characteristic of viruses transmitted from mother to infant. However, our data suggest that a limited number of PNGS that seem to be conserved in all variants in infants but are not uniformly present in variants in mothers may confer an advantage for transmission of the virus, thereby highlighting the potentially important role of the 'glycan shield.' This finding was particularly significant for the PNGS at positions N301 and N384. Copyright © 2008 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

We analyzed the association between mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) and maternal neutralizing antibodies to heterologous primary isolates of various HIV-1 clades, to test the hypothesis that protective antibodies are those with broad neutralizing activity. Our study sample included 90 Thai women for whom the timing of HIV-1 transmission (in utero or intrapartum) was known. The statistical analysis included a conditional logistic-regression model to control for both plasma viral load and duration of zidovudine prophylaxis. The higher the titer of neutralizing antibodies to a heterologous strain of the same clade, the lower the rate of MTCT of HIV-1. More specifically, high levels of neutralizing antibodies to the MBA (CRF01_AE) strain were associated with low intrapartum transmission of HIV-1. This suggested that such heterologous neutralizing antibodies may be involved in the natural prevention of late perinatal HIV transmission. These data are consistent with the hypothesis that the use of some antibodies might help to prevent perinatal HIV transmission, through passive immunoprophylaxis. Moreover, the study of humoral factors associated with MTCT of HIV-1 may identify correlates of protection that should help in the design of efficient HIV/acquired immunodeficiency syndrome vaccines. © 2006 by the Infectious Diseases Society of America. All rights reserved. [ABSTRACT FROM AUTHOR]

Background: A single intrapartum dose of nevirapine for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) leads to the selection of resistance mutations. Whether there are clinically significant consequences in mothers who are subsequently treated with a nevirapine-containing regimen is unknown.Methods: We randomly assigned 1844 women in Thailand who received zidovudine during the third trimester of pregnancy to receive intrapartum nevirapine or placebo. In the postpartum period, 269 of the women with a CD4 count below 250 cells per cubic millimeter began a nevirapine-containing antiretroviral regimen. Plasma samples were obtained 10 days post partum and analyzed for resistance mutations. Plasma HIV type 1 (HIV-1) RNA was measured before the initiation of therapy and three and six months thereafter.Results: After six months of therapy, the HIV-1 RNA level was less than 50 copies per milliliter in 49 percent of the women who had received intrapartum nevirapine, as compared with 68 percent of the women who had not received intrapartum nevirapine (P=0.03). Resistance mutations to nonnucleoside reverse-transcriptase inhibitors were detectable in blood samples obtained 10 days post partum from 32 percent of the women who had received intrapartum nevirapine; the most frequent mutations were K103N, G190A, and Y181C. Among the women who had received intrapartum nevirapine, viral suppression was achieved at six months in 38 percent of those with resistance mutations and 52 percent of those without resistance mutations (P=0.08). An HIV-1 RNA level at or above the median of 4.53 log10 copies per milliliter before therapy and intrapartum exposure to nevirapine were independently associated with virologic failure. After six months of therapy, there was no significant difference between groups in the CD4 count (P=0.65).Conclusions: Women who received intrapartum nevirapine were less likely to have virologic suppression after six months of postpartum treatment with a nevirapine-containing regimen. Our data suggest the need for strategies to maximize the benefits of both antiretroviral prophylaxis against mother-to-child transmission of HIV and antiretroviral therapy for mothers. [ABSTRACT FROM AUTHOR]

Presents several abstracts related to antiretroviral therapy. 'Chronic Hyperlactatemia in HIV-infected Patients Taking Antiretroviral Therapy,' by M. John, C.B. Moore, I.R. James, D. Nolan, R.P. Upton, E.J. McKinnon, et al published in the 2001 issue of 'AIDS' journal; 'Immunologic and Virologic Response to Highly Active Antiretroviral Therapy in the Multicenter AIDS Cohort Study,' by T.E. Yamashita, J.P. Phair, A. Munoz, J.B. Margolick, R. Detels, S.J. O'Brien, et al published in the 2001 issue of 'AIDS' journal.

Purpose of the study Previous studies evaluating the frequency of CXCR4-using strains in HIV-1 vertically infected children restricted mainly to patients infected with subtype B or C strains. However, the coreceptor use by non-B or non-C subtypes remains little known, especially in infants. In this study, we determined the HIV-1 coreceptor usage in infants with vertically-acquired HIV-1 infection in Thailand, where the predominant circulating HIV-1 strains are CRF01_AE and the minority are subtype B. Methods C2-V3-C3 gp120 was amplified in a triplicate nested-PCR and sequenced. Coreceptor usage was predicted using the geno2pheno [coreceptor] algorithm and analyzed with a false positive rate (FRP) of 10%. Summary of results A total of 255 sequences were obtained from viral isolates of 85 HIV-1-infected infants (34 male and 51 female) participating in the National AIDS Program (NAP) of the National Health Security Office (NHSO) of Thailand. All children were received ARV prophylaxis according to the Thai national guidelines. The median age was 84 days (range: 33-308). Seventy-four children (87.1%) were infected with CRF01_AE strain and 11 (12.9%) were infected with subtype B strain. Concordance in tropism prediction for the triplicates was observed in all samples. CXCR4 coreceptor-using strains were found in 44.7% (38 of 85) and CCR5 coreceptor-using strains were found in 55.3% (47 of 85). No significant difference in age (p=0.34) and clinical signs of AIDS (p=0.47) were observed between these populations. CCR5Delta32 and CCR5m303 mutation genotypes that may contribute to a selective pressure of viruses to alternatively use CXCR4 as a coreceptor were not found. Conclusions A high prevalence of HIV-1 CXCR4-using variants was found among HIV-1 vertically infected infants in Thailand, indicating that a direct vertical transmission of CXCR4-using variants or a rapid switch from CCR5-using to CXCR4-using viruses shortly after transmission. These observations may have implications for clinical and therapeutic aspects, especially in the early stage of HIV-1 infection in infants and may benefits for using of CCR5-antagonists in this population. [ABSTRACT FROM AUTHOR]

Background: Although zidovudine prophylaxis decreases the rate of transmission of the human immunodeficiency virus (HIV) type 1 substantially, a large number of infants still become infected. We hypothesized that the administration, in addition to zidovudine, of a single dose of oral nevirapine to mothers during labor and to neonates would further reduce transmission of HIV.Methods: We conducted a randomized, double-blind trial of three treatment regimens in Thai women who were receiving zidovudine therapy during the third trimester of pregnancy. In one group, mothers and infants received a single dose of nevirapine (nevirapine-nevirapine regimen); in another, mothers and infants received nevirapine and placebo, respectively (nevirapine-placebo regimen); and in the last, mothers and infants received placebo (placebo-placebo regimen). The infants also received one week of zidovudine therapy and were formula-fed. The end point of the study was infection with HIV in the infants, established by virologic testing.Results: Between January 15, 2001, and February 28, 2003, a total of 1844 Thai women were enrolled. At the first interim analysis, the independent data monitoring committee stopped enrollment in the placebo-placebo group. Among women who delivered before the interim analysis, the as-randomized Kaplan-Meier estimates of the transmission rates were 1.1 percent (95 percent confidence interval, 0.3 to 2.2) in the nevirapine-nevirapine group and 6.3 percent (95 percent confidence interval, 3.8 to 8.9) in the placebo-placebo group (P<0.001). The final per-protocol transmission rate in the nevirapine-nevirapine group, 1.9 percent (95 percent confidence interval, 0.9 to 3.0), was not significantly inferior to the rate in the nevirapine-placebo group (2.8 percent; 95 percent confidence interval, 1.5 to 4.1). Nevirapine had an effect within subgroups defined by known risk factors such as viral load and CD4 count. No serious adverse effects were associated with nevirapine therapy.Conclusions: A single dose of nevirapine to the mother, with or without a dose of nevirapine to the infant, added to oral zidovudine prophylaxis starting at 28 weeks' gestation, is highly effective in reducing mother-to-child transmission of HIV. [ABSTRACT FROM AUTHOR]