Cell-Free (RNA) and Cell-Associated (DNA) HIV-1 and Postnatal Transmission through Breastfeeding

Introduction

Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.

Materials and Methods

Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.

Results

There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively].

Conclusions

The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.     

HIV-1 Autologous Antibody Neutralization Associates with Mother to Child Transmission

The HIV-1 characteristics associated with mother to child transmission (MTCT) are still poorly understood and if known would indicate where intervention strategies should be targeted. In contrast to horizontally infected individuals, exposed infants possess inherited antibodies (Abs) from their mother with the potential to protect against infection. We investigated the HIV-1 gp160 envelope proteins from seven transmitting mothers (TM) whose children were infected either during gestation or soon after delivery and from four non-transmitting mothers (NTM) with similar viral loads and CD4 counts. Using pseudo-typed viruses we tested gp160 envelope glycoproteins for TZM-bl infectivity, CD4 and CCR5 interactions, DC-SIGN capture and transfer and neutralization with an array of common neutralizing Abs (NAbs) (2F5, 2G12, 4E10 and b12) as well as mother and infant plasma. We found no viral correlates associated with HIV-1 MTCT nor did we find differences in neutralization with the panel of NAbs. We did, however, find that TM possessed significantly higher plasma neutralization capacities than NTM (P  = 0.002). Furthermore, we found that in utero (IU) TM had a higher neutralization capacity than mothers transmitting either peri - partum (PP) or via breastfeeding (BF) (P  = 0.002). Plasma from children infected IU neutralized viruses carrying autologous gp160 viral envelopes as well as those from their corresponding mothers whilst plasma from children infected PP and/or BF demonstrated poor neutralizing capacity. Our results demonstrate heightened autologous NAb responses against gp120/gp41 can associate with a greater risk of HIV-1 MTCT and more specifically in those infants infected IU. Although the number of HIV-1 transmitting pairs is low our results indicate that autologous NAb responses in mothers and infants do not protect against MTCT and may in fact be detrimental when considering IU HIV-1 transmissions.     

Frequent detection of escape from cytotoxic T-lymphocyte recognition in perinatal human immunodeficiency virus (HIV) type 1 transmission: the ariel project for the prevention of transmission of HIV from mother to infant

Host immunologic factors, including human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL), are thought to contribute to the control of HIV type 1 (HIV-1) replication and thus delay disease progression in infected individuals. Host immunologic factors are also likely to influence perinatal transmission of HIV-1 from infected mother to infant. In this study, the potential role of CTL in modulating HIV-1 transmission from mother to infant was examined in 11 HIV-1-infected mothers, 3 of whom transmitted virus to their offspring. Frequencies of HIV-1-specific human leukocyte antigen class I-restricted CTL responses and viral epitope amino acid sequence variation were determined in the mothers and their infected infants. Maternal HIV-1-specific CTL clones were derived from each of the HIV-1-infected pregnant women. Amino acid substitutions within the targeted CTL epitopes were more frequently identified in transmitting mothers than in nontransmitting mothers, and immune escape from CTL recognition was detected in all three transmitting mothers but in only one of eight nontransmitting mothers. The majority of viral sequences obtained from the HIV-1-infected infant blood samples were susceptible to maternal CTL. These findings demonstrate that epitope amino acid sequence variation and escape from CTL recognition occur more frequently in mothers that transmit HIV-1 to their infants than in those who do not. However, the transmitted virus can be a CTL susceptible form, suggesting inadequate in vivo immune control.     

Maternal SDF1 3'A polymorphism is associated with increased perinatal human immunodeficiency virus type 1 transmission

Genetic polymorphisms in chemokine and chemokine receptor genes influence susceptibility to human immunodeficiency virus type 1 (HIV-1) infection and disease progression, but little is known regarding the association between these allelic variations and the ability of the host to transmit virus. In this study, we show that the maternal heterozygous SDF1 genotype (SDF1 3'A/wt) is associated with perinatal transmission of HIV-1 (risk ratio [RR], 1.8; 95% confidence interval [CI], 1.0 to 3.3) and particularly postnatal breastmilk transmission (RR, 3.1; 95% CI, 1.1 to 8.6). In contrast, the infant SDF1 genotype had no effect on mother-to-infant transmission. These data suggest that SDF1, which is a ligand for the T-tropic HIV-1 coreceptor CXCR4, may affect the ability of a mother to transmit the virus to her infant. This suggests that a genetic polymorphism in a gene encoding a chemokine receptor ligand may be associated with increased infectivity of the index case and highlights the importance of considering transmission as well as clinical outcome in designing chemokine-based therapies for HIV-1.     

Modeling Maternal-Infant HIV Transmission in the Presence of Breastfeeding with an Imperfect Test

An important public health question is to determine the probabilities of perinatal HIV transmission and when it occurs, whether antepartum, intrapartum, or postpartum through breastfeeding. However, this is a difficult problem because the presence of HIV infection in an infant can only be ascertained through viral assays in the postpartum period. We propose a model that simultaneously estimates the risks of antepartum, intrapartum, and postpartum transmissions together with the sensitivity of the screening tests for HIV infection. The model allows estimating of infectivity through breast milk during postpartum periods. The methods are illustrated on a South African randomized clinical trial of extended AZT versus a short course of nevirapine in infants whose mothers had no access to antenatal antiretroviral therapy.     

The Role of HIV Replicative Fitness in Perinatal Transmission of HIV

Perinatal transmission of Human immunodeficiency virus(HIV),also called mother-to-child transmission(MTCT),accounts for 90% of infections in infants worldwide and occurs in 30%-45% of children born to untreated HIV-1 infected mothers.Among HIV-1 infected mothers,some viruses are transmitted from mothers to their infants while others are not.The relationship between virologic properties and the pathogenesis caused by HIV-1 remains unclear.Previous studies have demonstrated that one obvious source of selectiv...     

Breast Milk from Tanzanian Women Has Divergent Effects on Cell-Free and Cell-Associated HIV-1 Infection In Vitro

Transmission of HIV-1 during breastfeeding is a significant source of new pediatric infections in sub-Saharan Africa. Breast milk from HIV-positive mothers contains both cell-free and cell-associated virus; however, the impact of breast milk on HIV-1 infectivity remains poorly understood. In the present study, breast milk was collected from HIV-positive and HIV-negative Tanzanian women attending antenatal clinics in Dar es Salaam. Milk was analyzed for activity in vitro against both cell-free and cell-associated HIV-1. Potent inhibition of cell-free R5 and X4 HIV-1 occurred in the presence of milk from all donors regardless of HIV-1 serostatus. Inhibition of cell-free HIV-1 infection positively correlated with milk levels of sialyl-Lewis(X) from HIV-positive donors. In contrast, milk from 8 of 16 subjects enhanced infection with cell-associated HIV-1 regardless of donor serostatus. Milk from two of these subjects contained high levels of multiple pro-inflammatory cytokines including TNFα, IL-1β, IL-6, IL-8, MIP-1α, MIP-1β, MCP-1 and IP-10, and enhanced cell-associated HIV-1 infection at dilutions as high as 1∶500. These findings indicate that breast milk contains innate factors with divergent activity against cell-free and cell-associated HIV-1 in vitro. Enhancement of cell-associated HIV-1 infection by breast milk may be associated with inflammatory conditions in the mother and may contribute to infant infection during breastfeeding.     

The role of HIV replicative fitness in perinatal transmission of HIV

Perinatal transmission of Human immunodeficiency virus(HIV),also called mother-to-child transmission(MTCT),accounts for 90% of infections in infants worldwide and occurs in 30%-45% of children born to untreated HIV-1 infected mothers.Among HIV-1 infected mothers,some viruses are transmitted from mothers to their infants while others are not.The relationship between virologic properties and the pathogenesis caused by HIV-1 remains unclear.Previous studies have demonstrated that one obvious source of selective pressure in the perinatal transmission of HIV-1 is maternal neutralizing antibodies.Recent studies have shown that viruses which are successfully transmitted to the child have growth advantages over those not transmitted,when those two viruses are grown together.Furthermore,the higher fitness is determined by the gp120 protein of the virus envelope.This suggests that the selective transmission of viruses with higher fitness occurred exclusively,regardless of transmission routes.There are many factors contributing to the selective transmission and HIV replicative fitness is an important one that should not be neglected.This review summarizes current knowledge of the role of HIV replicative fitness in HIV MTCT transmission and the determinants of viral fitness upon MTCT.     

Replication and pathogenicity of human immunodeficiency virus type 1 accessory gene mutants in SCID-hu mice.

The functional roles of the human immunodeficiency virus type 1 (HIV-1) accessory genes (nef, vpr, vpu, and vif) are as yet unclear. Using the SCID-hu model system, we have examined the infectivity, replicative capacity, and pathogenicity of strains of the molecular clone HIV-1NL4-3 that contain deletion mutations in these individual accessory genes. We determined that deletion of these genes had differential effects on both infectivity and pathogenicity. Deletion of vpr had little or no effect on viral infectivity, replication, and pathogenicity; however, deletion of vpu or vif had a significant effect on infectivity and moderate effects on pathogenicity. nef-minus strains were the most attenuated in this system, demonstrating significantly lower levels of infectivity and pathogenicity. However, deletion of these individual genes attenuated but did not abrogate the pathogenic properties of HIV-1. Mutant viruses still retained the ability to induce thymocyte depletion to various degrees if implants were infected with higher doses of virus or observed for longer periods of time. The relative contributions of these genes to in vivo pathogenic potential should be taken into consideration when one is contemplating a live attenuated vaccine for HIV-1.     

Vaccine platform for prevention of tuberculosis and mother-to-child transmission of human immunodeficiency virus type 1 through breastfeeding

Most children in Africa receive their vaccine against tuberculosis at birth. Those infants born to human immunodeficiency virus type 1 (HIV-1)-positive mothers are at high risk of acquiring HIV-1 infection through breastfeeding in the first weeks of their lives. Thus, the development of a vaccine which would protect newborns against both of these major global killers is a logical yet highly scientifically, ethically, and practically challenging aim. Here, a recombinant lysine auxotroph of Mycobacterium bovis bacillus Calmette-Guérin (BCG), a BCG strain that is safer than those currently used and expresses an African HIV-1 clade-derived immunogen, was generated and shown to be stable and to induce durable, high-quality HIV-1-specific CD4⁺- and CD8⁺-T-cell responses. Furthermore, when the recombinant BCG vaccine was used in a priming-boosting regimen with heterologous components, the HIV-1-specific responses provided protection against surrogate virus challenge, and the recombinant BCG vaccine alone protected against aerosol challenge with M. tuberculosis. Thus, inserting an HIV-1-derived immunogen into the scheduled BCG vaccine delivered at or soon after birth may prime HIV-1-specific responses, which can be boosted by natural exposure to HIV-1 in the breast milk and/or by a heterologous vaccine such as recombinant modified vaccinia virus Ankara delivering the same immunogen, and decrease mother-to-child transmission of HIV-1 during breastfeeding.     

Inhibition of HIV-1 infectivity through an innate mechanism involving naturally occurring IgM anti-leukocyte autoantibodies

In prior studies, we show that naturally occurring IgM anti-leukocyte autoantibodies (IgM-ALA) bind to CD3, CD4, CCR5, and CXCR4 receptors. These observations prompted us to determine whether IgM-ALA have a role in inhibiting HIV-1 infectivity by inhibiting viral entry into cells. We show that purified IgM, but not IgG, from individual sera of both normal and HIV-1 infected individuals is highly inhibitory (>95%) to HIV-1 viral infectivity both in vitro using PHA plus IL-2 activated PBL and in vivo using the human PBL-SCID mouse. Inhibition was observed with physiological doses of purified serum IgM and even after IgM was added 3 days postinfection in the in vitro assays. Absorbing purified serum IgM either with leukocytes or immobilized recombinant CD4 significantly decreased (>80%) the inhibitory effect on HIV-1 infectivity. IgM inhibited by >90% syncytia formation with the X4-IIIB infected SupT-1 cells indicating therefore that IgM inhibits viral attachment to core-receptors. IgM mediated anti-HIV-1 activity was highly specific as only certain IgM-ALA, obtained from human B cell clones inhibited HIV-1. IgM from certain HIV-1 infected individuals were not inhibitory to some R5-HIV-1 viral strains indicating that certain HIV-IgM may lack Abs reactive to strain specific coreceptor epitopes. These data indicate that an innate immune mechanism which is present from birth i.e., IgM-ALA, has a role in inhibiting HIV-1 viral entry into cells. Validation of this data with other in vivo models will be needed to determine whether in vivo administration or enhancement of IgM-ALA, e.g., through a vaccine, could prolong the asymptomatic state in HIV-1 infected individuals.     

The breadth and potency of passively acquired human immunodeficiency virus type 1-specific neutralizing antibodies do not correlate with the risk of infant infection

Although a major goal of human immunodeficiency virus type 1 (HIV-1) vaccine efforts is to elicit broad and potent neutralizing antibodies (NAbs), there are no data that directly demonstrate a role for such NAbs in protection from HIV-1 infection in exposed humans. The setting of mother-to-child transmission provides an opportunity to examine whether NAbs provide protection from HIV-1 infection because infants acquire passive antibodies from their mothers prior to exposure to HIV-1 through breastfeeding. We evaluated the characteristics of HIV-1-specific NAbs in 100 breast-fed infants of HIV-1-positive mothers who were HIV-1 negative at birth and monitored them until age 2. A panel of eight viruses that included variants representative of those in the study region as well as more diverse strains was used to determine the breadth of the infant NAbs. From their mothers, infants acquired broad and potent NAbs that were capable of recognizing heterologous circulating HIV-1 variants of diverse subtypes, but the presence of NAbs of broad HIV-1 specificity was not associated with transmission risk. There was also no correlation between responses to any particular virus tested, which included a range of diverse variants that demonstrated different neutralization profiles, including recognition by specific antibodies with known epitope targets. The eight viruses tested exhibited neutralization profiles to a variety of monoclonal antibodies (2F5, PG9, and VRC01) similar to those of viruses present in pregnant women in the cohort. These results suggest that the breadth and potency of the heterologous antibody response in exposed infants, measured against a virus panel comprised of variants typical of those circulating in the population, does not predict protection.     

Multiploid inheritance of HIV-1 during cell-to-cell infection

During cell-to-cell transmission of human immunodeficiency virus type 1 (HIV-1), many viral particles can be simultaneously transferred from infected to uninfected CD4 T cells through structures called virological synapses (VS). Here we directly examine how cell-free and cell-to-cell infections differ from infections initiated with cell-free virus in the number of genetic copies that are transmitted from one generation to the next, i.e., the genetic inheritance. Following exposure to HIV-1-expressing cells, we show that target cells with high viral uptake are much more likely to become infected. Using T cells that coexpress distinct fluorescent HIV-1 variants, we show that multiple copies of HIV-1 can be cotransmitted across a single VS. In contrast to cell-free HIV-1 infection, which titrates with Poisson statistics, the titration of cell-associated HIV-1 to low rates of overall infection generates a constant fraction of the newly infected cells that are cofluorescent. Triple infection was also readily detected when cells expressing three fluorescent viruses were used as donor cells. A computational model and a statistical model are presented to estimate the degree to which cofluorescence underestimates coinfection frequency. Lastly, direct detection of HIV-1 proviruses using fluorescence in situ hybridization confirmed that significantly more HIV-1 DNA copies are found in primary T cells infected with cell-associated virus than in those infected with cell-free virus. Together, the data suggest that multiploid inheritance is common during cell-to-cell HIV-1 infection. From this study, we suggest that cell-to-cell infection may explain the high copy numbers of proviruses found in infected cells in vivo and may provide a mechanism through which HIV preserves sequence heterogeneity in viral quasispecies through genetic complementation.     

Maternal-fetal transmission of human immunodeficiency virus

The World Health Organization estimates that by year 2000, 10 million children will be infected with human immunodeficiency virus type 1 (HIV-1) at birth and will subsequently develop AIDS. Perinatally acquired infections account for the majority of all HIV-1 cases in children, with an estimated mother-to-infant transmission rate of more than 30%. It is not clear why more than half of the children born to HIV-1-infected mothers are uninfected. Maternal transmission of HIV-1 occurs at three levels: prepartum, intrapartum, and postpartum. Several maternal parameters including advanced clinical stages of the mother, low CD4+ lymphocyte counts, maternal immune response to HIV-1, recent infection, high level of circulating HIV-1, and maternal disease progression have been implicated in an increased risk of mother-to-infant transmission of HIV-1. Viral factors influencing mother-to-infant transmission are not known. Furthermore, several other factors such as acute infection during pregnancy, presence of other sexually transmitted diseases (STD) or other chronic infections, vaginal bleeding, disruption of placental integrity, premature rupture of membrane (PROM), and preterm PROM have been associated with mother-to-infant transmission of HIV-1. In addition, tobacco and cigarette smoking during pregnancy have been shown to triple the rate of maternal transmission of HIV-1. The AIDS Clinical Trial Group (ACTG) suggested that zidovudine (ZDV) can reduce the rate of mother-to-infant transmission of HIV-1 if administered to HIV-1-infected pregnant women with CD4 counts greater than 200. Moreover, this study failed to take into consideration several factors that may influence maternal transmission of HIV-1. However, the molecular mechanisms involved in mother-to-infant transmission of HIV-1 are not understood, which makes it more difficult to define strategies for effective treatment and prevention of HIV-1 infection in children. Several groups are engaged in the understanding of the molecular and biological properties of HIV-1 influencing mother-to-infant transmission. Results from my and several other laboratories suggest that the minor genotypes, subtypes, or variants of HIV-1 found in a genetically heterogeneous virus population of infected mothers are transmitted to their infants. The minor HIV-1 genotype predominates initially as a homogeneous population in the infant and then becomes diverse as the infant matures. Furthermore, transmission of a major or multiple HIV-1 genotypes from mother to infant has been reported. Taken together, these results strongly suggest that there are differences among the molecular and biological properties of the maternal variants that are transmitted to the infants and the maternal variants that are not transmitted to the infants. The understanding of the molecular and biological properties of the transmitted viruses will enable researchers to target a particular subtype in the mothers that is transmitted to the infants.     

Mother-to-child transmission of HIV in Botswana: an ethical perspective on mandatory testing

Mother-to-child transmission (MTCT) of HIV represents a particularly dramatic aspect of the HIV epidemic with an estimated 600,000 newborns infected yearly, 90% of them living in sub-Saharan Africa. Since the beginning of the HIV epidemic, an estimated 5.1 million children worldwide have been infected with HIV. MTCT is responsible for 90% of these infections. Two-thirds of the MTCT are believed to occur during pregnancy and delivery, and about one-third through breastfeeding. As the number of women of child bearing age infected with HIV rises, so does the number of infected children. It is apparent that voluntary testing in Botswana has made some valuable inroads in decreasing perinatal HIV transmission, but the statistics showing the increased rate of HIV infection among women 15-24 years of age are not very promising. After reviewing all the pertinent scientific data it is clear that mandatory HIV testing of all pregnant women in conjunction with the implementation of a full package of interventions would save thousands of lives -- mothers, newborns and others who could be infected as a result of these women not being aware of their HIV status. If the protection and preservation of human life is a priority in Botswana, then it is time to allow for mandatory HIV testing of all pregnant women, before it is too late for those who are the most vulnerable. To do less would be medically inappropriate and ethically irresponsible.     

The human immunodeficiency virus type 1 envelope confers higher rates of replicative fitness to perinatally transmitted viruses than to nontransmitted viruses

Selection of a minor viral genotype during perinatal transmission of human Immunodeficiency virus type 1 (HIV-1) has been observed, but there is a lack of information on the correlation of the restrictive transmission with biological properties of the virus, such as replicative fitness. Recombinant viruses expressing the enhanced green fluorescent protein or the Discosoma sp. red fluorescent (DsRed2) protein carrying the V1 to V5 regions of env from seven mother-infant pairs (MIPs) infected by subtype C HIV-1 were constructed, and competition assays were carried out to compare the fitness between the transmitted and nontransmitted viruses. Flow cytometry was used to quantify the frequency of infected cells, and the replicative fitness was determined based on a calculation that takes into account replication of competing viruses in a single infection versus dual infections. Transmitted viruses from five MIPs with the mothers chronically infected showed a restrictive env genotype, and all the recombinant viruses carrying the infants' Env had higher replicative fitness than those carrying the Env from the mothers. This growth fitness is lineage specific and can be observed only within the same MIP. In contrast, in two MIPs where the mothers had undergone recent acute infection, the viral Env sequences were similar between the mothers and infants and showed no further restriction in quasispecies during perinatal transmission. The recombinant viruses carrying the Env from the infants' viruses also showed replication fitness similar to those carrying the mothers' Env proteins. Our results suggest that newly transmitted viruses from chronically infected mothers have been selected to have higher replicative fitness to favor transmission, and this advantage is conferred by the V1 to V5 region of Env of the transmitted viruses. This finding has important implications for vaccine design or development of strategies to prevent HIV-1 transmission.     

Inflammatory Genital Infections Mitigate a Severe Genetic Bottleneck in Heterosexual Transmission of Subtype A and C HIV-1

The HIV-1 epidemic in sub-Saharan Africa is driven largely by heterosexual transmission of non-subtype B viruses, of which subtypes C and A are predominant. Previous studies of subtype B and subtype C transmission pairs have suggested that a single variant from the chronically infected partner can establish infection in their newly infected partner. However, in subtype A infected individuals from a sex worker cohort and subtype B individuals from STD clinics, infection was frequently established by multiple variants. This study examined over 1750 single-genome amplified viral sequences derived from epidemiologically linked subtype C and subtype A transmission pairs very early after infection. In 90% (18/20) of the pairs, HIV-1 infection is initiated by a single viral variant that is derived from the quasispecies of the transmitting partner. In addition, the virus initiating infection in individuals who were infected by someone other than their spouse was characterized to determine if genital infections mitigated the severe genetic bottleneck observed in a majority of epidemiologically linked heterosexual HIV-1 transmission events. In nearly 50% (3/7) of individuals infected by someone other than their spouse, multiple genetic variants from a single individual established infection. A statistically significant association was observed between infection by multiple genetic variants and an inflammatory genital infection in the newly infected individual. Thus, in the vast majority of HIV-1 transmission events in cohabiting heterosexual couples, a single genetic variant establishes infection. Nevertheless, this severe genetic bottleneck can be mitigated by the presence of inflammatory genital infections in the at risk partner, suggesting that this restriction on genetic diversity is imposed in large part by the mucosal barrier.     

The Breadth and Titer of Maternal HIV-1-Specific Heterologous Neutralizing Antibodies Are Not Associated with a Lower Rate of Mother-to-Child Transmission of HIV-1

It has been hypothesized that neutralizing antibodies (NAbs) should have broad specificity to be effective in protection against diverse HIV-1 variants. The mother-to-child transmission model of HIV-1 provides the opportunity to examine whether the breadth of maternal NAbs is associated with protection of infants from infection. Samples were obtained at delivery from 57 transmitting mothers (T) matched with 57 nontransmitting mothers (NT) enrolled in the multicenter French perinatal cohort (ANRS EPF CO1) between 1990 and 1996. Sixty-eight (59.6%) and 46 (40.4%) women were infected by B and non-B viruses, respectively. Neutralization assays were carried out with TZM-bl cells, using a panel of 10 primary isolates of 6 clades (A, B, C, F, CRF01_AE, and CRF02_AG), selected for their moderate or low sensitivity to neutralization. Neutralization breadths were not statistically different between T and NT mothers. However, a few statistically significant differences were observed, with higher frequencies or titers of NAbs toward several individual strains for NT mothers when the clade B-infected or non-clade B-infected mothers were analyzed separately. Our study confirms that the breadth of maternal NAbs is not associated with protection of infants from infection.     

Genetic analysis of human immunodeficiency virus type 1 envelope V3 region isolates from mothers and infants after perinatal transmission.

The human immunodeficiency virus type 1 (HIV-1) sequences from variable region 3 (V3) of the envelope gene were analyzed from seven infected mother-infant pairs following perinatal transmission. The V3 region sequences directly derived from the DNA of the uncultured peripheral blood mononuclear cells from infected mothers displayed a heterogeneous population. In contrast, the infants' sequences were less diverse than those of their mothers. In addition, the sequences from the younger infants' peripheral blood mononuclear cell DNA were more homogeneous than the older infants' sequences. All infants' sequences were different but displayed patterns similar to those seen in their mothers. In the mother-infant pair sequences analyzed, a minor genotype or subtype found in the mothers predominated in their infants. The conserved N-linked glycosylation site proximal to the first cysteine of the V3 loop was absent only in one infant's sequence set and in some variants of two other infants' sequences. Furthermore, the HIV-1 sequences of the epidemiologically linked mother-infant pairs were closer than the sequences of epidemiologically unlinked individuals, suggesting that the sequence comparison of mother-infant pairs done in order to identify genetic variants transmitted from mother to infant could be performed even in older infants. There was no evidence for transmission of a major genotype or multiple genotypes from mother to infant. In conclusion, a minor genotype of maternal virus is transmitted to the infants, and this finding could be useful in developing strategies to prevent maternal transmission of HIV-1 by means of perinatal interventions.     

Factors affecting intention to breastfeed among Syrian and Jordanian mothers: a comparative cross-sectional study

Background

Breastfeeding remains normative and vital for child survival in the developing world. However, knowledge of the risk of Human Immunodeficiency Virus (HIV) transmission through breastfeeding has brought to attention the controversy of whether breastfeeding can be safely practiced by HIV positive mothers. Prevention of mother to child transmission (PMTCT) programs provide prevention services to HIV positive mothers including infant feeding counseling based on international guidelines. This study aimed at exploring infant feeding choices and how breastfeeding and the risk of HIV transmission through breastfeeding was interpreted among HIV positive mothers and their counselors in PMTCT programs in Addis Ababa, Ethiopia.

Methods

The study was conducted in the PMTCT clinics in two governmental hospitals in Addis Ababa, Ethiopia, using qualitative interviews and participant observation. Twenty two HIV positive mothers and ten health professionals working in PMTCT clinics were interviewed.

Results

The study revealed that HIV positive mothers have developed an immense fear of breast milk which is out of proportion compared to the evidence of risk of transmission documented. The fear is expressed through avoidance of breastfeeding or, if no other choice is available, through an intense unease with the breastfeeding situation, and through expressions of sin, guilt, blame and regret. Health professionals working in the PMTCT programs seemed to largely share the fear of HIV positive mother's breast milk, and their anxiety was reflected in the counseling services they provided. Formula feeding was the preferred infant feeding method, and was chosen also by HIV positive women who had to beg in the streets for survival.

Conclusions

The fear of breast milk that seems to have developed among counselors and HIV positive mothers in the wake of the HIV epidemic may challenge a well established breastfeeding culture and calls for public health action. Based on strong evidence of the risks when infants are not exclusively breastfed, there is a great need to protect breastfeeding from pressures of replacement feeding and to promote exclusive breastfeeding as the best infant feeding option for HIV positive and HIV negative mothers alike.