Preventing postnatal transmission of HIV-1 through breast-feeding: modifying infant feeding practices

Approaches to reducing or preventing the risk of postnatal transmission through breast-feeding include the avoidance of all breast-feeding and the use of exclusive replacement feeds or exclusive breast-feeding for a limited duration with early and rapid cessation of breast-feeding around 4-6 months of age. The efficacy and safety of the latter approach have not been established and studies are in progress to provide further information. In addition, inactivation of HIV in breast milk would allow breast-feeding to continue while reducing the risk of postnatal transmission of HIV and may be usefully applied in certain circumstances, such as for premature infants or while a mother recovers from mastitis. In this review, experience is reported from clinical trials or studies additional to their main objective of assessing rates and risk factors for mother-to-child transmission. This may inform policy, programming, and training options and may be especially valuable in the absence of conclusive data on the efficacy of the interventions to be applied during the breast-feeding period.     

Potential cost-effectiveness of maternal and infant antiretroviral interventions to prevent mother-to-child transmission during breast-feeding

INTRODUCTION: One-third of maternal-to-child HIV transmission occurs during breast-feeding (BF). Several trials are currently evaluating the efficacy of postpartum antiretrovirals to reduce BF transmission. METHODS: This study used Markov modeling to define the circumstances under which the following interventions would be cost-effective: BF for 6 months with daily infant nevirapine (NVP) prophylaxis; maternal combination antiretroviral therapy (ART) during pregnancy and for 6 months of BF; and maternal combination ART only for women who meet CD4 criteria. Each was compared to: BF for 12 months; BF for 6 months; and formula feeding for 12 months. Strategies were evaluated for a hypothetical cohort of 40,000 pregnant women in sub-Saharan Africa, in the context of available voluntary counseling and testing in antenatal care. Model estimates were derived from the literature and local sources. Sensitivity analyses were performed on uncertain estimates. The perspective used was that of a government health district. RESULTS: Using base case estimates, BF for 6 months was the economically preferred strategy: it cost 806,995 dollars and generated 446,208 quality-adjusted life-years (QALYs). Providing daily infant NVP cost an additional 93,638 dollars and generated 1183 additional QALYs, but its incremental cost-effectiveness ratio (ICER) of 79 dollars/QALY exceeded the standard willingness to pay (64 dollars/QALY) for most resource-poor settings. Maternal combination ART was potentially very effective but too costly for most resource-poor settings (ICER: 87 dollars/QALY). In order for daily infant NVP during BF to be preferred, it must have >/=44% relative efficacy or cost 相似文献   

Immunoprophylaxis to prevent mother-to-child transmission of HIV-1

Antiretroviral therapy can profoundly reduce the risk of mother-to-child transmission (MTCT) of HIV, but the drugs have a relatively short half-life and should thus be administered throughout breast-feeding to optimally prevent postnatal infection of the infant. The potential toxicities and the development of resistance may limit the long-term efficacy of antiretroviral prophylaxis, and a safe and effective active/passive immunoprophylaxis regimen, begun at birth, and potentially overlapping with interpartum or neonatal chemoprophylaxis, would pose an attractive alternative. This review draws on data presented at the Ghent Workshop on prevention of breast milk transmission and on selected issues from a workshop specifically relating to immunoprophylaxis held in Seattle in October 2002. This purpose of this review is to address the scientific rationale for the development of passive (antibody) and active (vaccine) immunization strategies for prevention of MTCT. Data regarding currently or imminently available passive and active immunoprophylaxis products are reviewed for their potential use in neonatal trials within the coming 1-2 years.     

Immune status and uptake of antiretroviral interventions to prevent mother-to-child transmission of HIV-1 in Africa

The aim of this study performed in Abidjan, C?te d'Ivoire, was to describe the distribution of CD4+ T-cell lymphocytes (CD4) in HIV-1-infected (HIV+) pregnant women diagnosed during prenatal voluntary counseling and testing and to assess whether HIV-related immunodeficiency influenced the acceptance of an antiretroviral (ARV) package (zidovudine beginning at 36 weeks of amenorrhea plus intrapartum nevirapine) to prevent mother-to-child transmission. Between April and June 2002, a CD4 count was systematically performed in all HIV+ women (n=221) in 5 antenatal clinics carrying out voluntary counseling and testing. No difference in CD4 count was found in HIV+ women who did not return for their test result (n=50) and those who were informed of their positive serostatus (n=171) (median CD4 count: 389/mm3 vs. 420/mm3; P=0.19). We also found a lack of difference in CD4 count in those who accepted ARV (n=72) and those who did not but knew their HIV status (n=99) (median CD4 count: 405/mm3 vs. 425/mm3; P=0.47). The overall uptake of the intervention (31.9%) appeared to be independent of the maternal immune status.     

HIV-1 reservoirs in breast milk and challenges to elimination of breast-feeding transmission of HIV-1

By compensating for the relative immaturity of the neonatal immune system, breast milk and breast-feeding prevent deaths in children. Nevertheless, transmission of HIV-1 through breast-feeding is responsible for more than half of new pediatric HIV infections. Recent studies of possible HIV-1 reservoirs in breast milk shed new light on features that influence HIV-1 transmission through breast-feeding. The particular characteristics of breast milk CD4(+) T cells that distinguish them from circulating blood lymphocytes (high frequency of cell activation and expression of memory and mucosal homing markers) facilitate the establishment of HIV-1 replication. Breast milk also contains a plethora of factors with anti-infectious, immunomodulatory, or anti-inflammatory properties that can regulate both viral replication and infant susceptibility. In addition, CD8(+) T lymphocytes, macrophages, and epithelial cells in breast milk can alter the dynamics of HIV-1 transmission. Even during efficient antiretroviral therapy, a residual stable, CD4(+) T cell-associated reservoir of HIV-1 is persistently present in breast milk, a likely source of infection. Only prophylactic treatment in infants--ideally with a long-acting drug, administered for the entire duration of breast-feeding--is likely to protect HIV-exposed babies against all forms of HIV transmission from breast milk, including cell-to-cell viral transfer.     

Transmission of cell-free and cell-associated HIV-1 through breast-feeding

BACKGROUND: Transmission through breast-feeding is an important cause of infant HIV-1 infections in developing countries; however, its mechanism remains largely unknown. We have explored the association between cell-free virus (CFV) and cell-associated virus (CAV) levels in breast milk (BM), as reflected by viral RNA and proviral DNA, respectively, and the risk of infant HIV-1 infection after 6 weeks postpartum. METHODS: Sixty-one HIV-positive mothers who transmitted HIV-1 by BM were matched to 61 HIV-positive nontransmitting mothers based on their infant's age at sample collection. CFV and CAV were quantified in a single milk specimen per mother preceding the infant's first HIV-positive result. RESULTS: After adjusting for maternal CD4 cell counts and disease stage, each 10-fold increase in CFV or CAV load was associated with an almost 3-fold increase in BM transmission. Whereas CAV load was predictive of transmission before and after 9 months postpartum, CFV was a significant predictor of transmission occurring only after 9 months. Phylogenetic analyses of the C2 to C5 env region showed that 85% of infants (11 of 13 infants) harboring viruses that clustered with CFV in their mother's milk were infected after 9 months postpartum. CONCLUSION: A reduction in milk CAV and CFV loads might significantly decrease HIV-1 transmission by breast-feeding.     

Mechanisms of HIV-1 escape from immune responses and antiretroviral drugs

Despite the fact that HIV-1 induces vigorous antiviral immune responses, viral replication is never completely controlled in infected individuals. Recent studies have provided insight into the mechanisms by which focused immune pressure directed at particular B or T cell epitopes leads to the rapid appearance of escape mutations. Even if anti-HIV-1 immune responses could be enhanced to the point where they inhibit viral replication to the same extent as certain combinations of antiretroviral drugs, eradication would be unlikely because of the persistence of the virus in an extremely stable latent reservoir in resting memory CD4(+) T cells.     

Subclinical mastitis, cell-associated HIV-1 shedding in breast milk, and breast-feeding transmission of HIV-1

BACKGROUND: Mastitis has been identified as a risk factor for mother-to-child transmission (MTCT) of HIV-1 through breast-feeding. It is unclear whether this association is mediated by increased cell-free virus (CFV) versus cell-associated virus (CAV) HIV shedding in breast milk. METHODS: We examined the risk of MTCT associated with subclinical mastitis and the relation between mastitis and CFV or CAV shedding in breast milk. Fifty-nine women who transmitted HIV through breast-feeding (cases) were individually matched to 59 nontransmitting controls nested in a cohort from Tanzania. For each case, we selected a milk specimen obtained before the infant's first positive test to quantify sodium (Na) and potassium (K) and measure CFV and CAV concentrations. Controls were matched on the child's age at the time of sample collection. RESULTS: Women with a breast milk Na/K ratio suggestive of mastitis (>1.0) had an 11-fold greater odds of transmission (95% confidence interval [CI]: 1.2 to 98.1), compared to women with a Na/K 相似文献   

Antenatal couple counseling increases uptake of interventions to prevent HIV-1 transmission

To determine effect of partner involvement and couple counseling on uptake of interventions to prevent HIV-1 transmission, women attending a Nairobi antenatal clinic were encouraged to return with partners for voluntary HIV-1 counseling and testing (VCT) and offered individual or couple posttest counseling. Nevirapine was provided to HIV-1-seropositive women and condoms distributed to all participants. Among 2104 women accepting testing, 308 (15%) had partners participate in VCT, of whom 116 (38%) were couple counseled. Thirty-two (10%) of 314 HIV-1-seropositive women came with partners for VCT; these women were 3-fold more likely to return for nevirapine (P = 0.02) and to report administering nevirapine at delivery (P = 0.009). Nevirapine use was reported by 88% of HIV-infected women who were couple counseled, 67% whose partners came but were not couple counseled, and 45%whose partners did not present for VCT (P for trend = 0.006). HIV-1-seropositive women receiving couple counseling were 5-fold more likely to avoid breast-feeding (P = 0.03) compared with those counseled individually. Partner notification of HIV-1-positive results was reported by 138 women (64%) and was associated with 4-fold greater likelihood of condom use (P = 0.004). Partner participation in VCT and couple counseling increased uptake of nevirapine and formula feeding. Antenatal couple counseling may be a useful strategy to promote HIV-1 prevention interventions.     

HIV-1 viral load and other risk factors for mother-to-child transmission of HIV-1 in a breast-feeding population in Cote d'Ivoire

Short-course antiretroviral regimens have been evaluated to reduce mother-to-child transmission of HIV in resource-limited settings. This report from Abidjan, Cote d'Ivoire, examines the risk factors for HIV transmission by 1 and 24 months among breast-feeding women. Eligible HIV-1-seropositive pregnant women enrolled in this randomized double-blind clinical trial were randomly assigned to receive either oral zidovudine (ZDV) (n = 126) prophylaxis or placebo (n = 124). Maternal prophylaxis began at 36 weeks of gestation (300 mg ZDV twice daily antepartum and 300 mg every 3 hours intrapartum); there was no neonatal prophylaxis component. The cumulative risk of transmission in the treatment group was 11.9% and 22.1% by 1 and 24 months, respectively. In adjusted analyses, viral load at enrollment was the strongest predictor of transmission (per log increment: odds ratio [OR] = 4.8, 95% confidence interval [CI]: 2.5-9.5 at 1 month; OR = 5.7; 95% CI: 3.1-10.8 at 24 months). Overall, ZDV prophylaxis was not significantly protective for infection at 1 or 24 months. Comparing ZDV with placebo following dichotomization of viral load (<50,000 vs. > or =50,000 copies/mL) at enrollment, however, there was a significant effect of ZDV seen only among those women with a low viral load at enrollment. The substantial risk of transmission despite ZDV prophylaxis, particularly among those with higher viral loads, underscores the need to find more effective regimens appropriate for use in resource-limited settings.     

Prevention of HIV transmission through breast-feeding: strengthening the research agenda

Mother-to-child transmission of HIV through breast-feeding is the remaining challenge facing mothers in resource-poor settings with a high HIV prevalence. Nearly all infants in developing countries are initially breast-fed, and most children continue to receive some breast-feeding until at least 6 months of age but frequently into the 2nd year of life, especially in sub-Saharan Africa and Asia. In December 2002, international researchers convened in Ghent, Belgium, to discuss mechanisms for, rates and risk factors of, and approaches to prevention of HIV transmission through breast-feeding. Four papers were compiled bringing together the presentation and discussions during this workshop, while the fourth paper also benefits from presentation made during an earlier workshop on vaccines in the prevention of mother-to-child transmission. These papers summarize the current state of knowledge and highlight the outstanding issues that will need to be addressed in the very near future before research advances can be translated into public health practice.