Vertical Transmission Of Human Immunodeficiency Virus Type 1 Research Articles

A study using knowledge, attitude and practices on the prevention of HIV-1 vertical transmission with outcomes in early infant HIV-1 diagnosis in Eastern Uganda

ObjectiveThe objective of this study was to assess trends over time using knowledge, attitude and practices (KAP) among mothers living with HIV and rates of early infant diagnosis (EID) of human immunodeficiency virus type 1 (HIV-1) in a hospital in Eastern Uganda, which is included in the National HIV Prevention Strategy (NHPS) in Uganda. MethodsA thematic qualitative assessment was conducted using focus group discussions (FGDs) with pregnant women, breastfeeding mothers and women attending the antiretroviral therapy (ART) clinic, all living with HIV. In addition, we have performed key informant interviews (KIIs) in October 2011 (baseline) and November 2016 (follow-up) at Mbale Regional Referral Hospital. Data were captured through customised source documents, written narratives and voice recordings. Social scientists decoded, analysed and interpreted the qualitative data with quality control. Retrospective data were obtained from EID registers for 2010 before and 2015 at the end of the NHPS, respectively. Supplementary quantitative data from the same hospital regarding trends of HIV-1 vertical transmission rates were collected from EID registers at baseline and at follow-up. Comparisons were made between HIV-1 transmission rates and KAP levels at baseline and at follow-up. ResultsThree paired sets of FGD sessions, consisting of 8–10 participants for each of the groups of pregnant women, breastfeeding mothers and women attending ART clinic, all living with HIV, were conducted at baseline and at follow-up. Age ranged from 17 to 40 years. Two sets of paired KII interviews corresponding to the periods before and after the NHPS were also held. All study FGDs and KIIs showed improvement in KAP on HIV-1 vertical transmission and lower EID rates when comparing baseline to the follow-up period [9/69 (13.0%) and 14/336 (4.2%)], respectively (P = 0.004). ConclusionImprovement was noted in KAP on HIV-1 vertical transmission in pregnant women, breastfeeding mothers and women attending ART clinic, all HIV positive, in a regional referral hospital in Eastern Uganda over a 5-year period and was associated with a reduction in vertical transmission rates. Our data suggest that KAP is an effective type of intervention with regard to the prevention of HIV-1 vertical transmission in this population in resource-limited settings.

Modeling mucosal cell-associated HIV type 1 transmission in vitro.

Human immunodeficiency virus type 1 (HIV-1) can efficiently spread by direct cell-to-cell contact, a mechanism termed cell-associated HIV transmission. By some estimates, cell-associated HIV transmission is 10-1000-fold more effective than cell-free HIV infection. Mucosal cell-associated HIV transmission may occur when HIV-bearing cells in mucosal secretions from an HIV-infected donor transfer virus directly to recipient target cells in or below the mucosal epithelium, or through HIV transcytosis across the mucosal epithelium of a noninfected host. This mechanism may play an important role in the sexual and vertical transmission of HIV-1, yet most in vitro tests of vaccine and microbicide efficacy assess cell-free virus transmission. This article reviews in vitro assays that have been used to model mucosal cell-associated transmission, including microscopy, immune cell cocultures, use of HIV-infected cells in epithelial cell transcytosis assays, and cell-associated infection of mucosal tissue explants. Assays that authentically simulate mucosal cell-associated HIV transmission could provide valuable insight into mechanisms and molecules that can potentially be targeted for HIV prevention, as well as critical models for testing novel HIV prevention strategies for efficacy against cell-associated HIV transmission.

Variability of HIV-1 Genomes among Children and Adolescents from São Paulo, Brazil

BackgroundGenetic variability is a major feature of the human immunodeficiency virus type 1 (HIV-1) and considered the key factor to frustrating efforts to halt the virus epidemic. In this study, we aimed to investigate the genetic variability of HIV-1 strains among children and adolescents born from 1992 to 2009 in the state of Sao Paulo, Brazil.MethodologyPlasma and peripheral blood mononuclear cells (PBMC) were collected from 51 HIV-1-positive children and adolescents on ART followed between September 1992 and July 2009. After extraction, the genetic materials were used in a polymerase chain reaction (PCR) to amplify the viral near full length genomes (NFLGs) from 5 overlapped fragments. NFLGs and partial amplicons were directly sequenced and data were phylogenetically inferred.ResultsOf the 51 samples studied, the NFLGs and partial fragments of HIV-1 from 42 PBMCs and 25 plasma were successfully subtyped. Results based on proviral DNA revealed that 22 (52.4%) patients were infected with subtype B, 16 (38.1%) were infected with BF1 mosaic variants and 4 (9.5%) were infected with sub-subtype F1. All the BF1 recombinants were unique and distinct from any previously identified unique or circulating recombinant forms in South America. Evidence of dual infections was detected in 3 patients coinfected with the same or distinct HIV-1 subtypes. Ten of the 31 (32.2%) and 12 of the 21 (57.1%) subjects with recovered proviral and plasma, respectively, protease sequences were infected with major mutants resistant to protease inhibitors. The V3 sequences of 14 patients with available sequences from PBMC/or plasma were predicted to be R5-tropic virus except for two patients who harbored an X4 strain.ConclusionsThe high proportion of HIV-1 BF1 recombinant, coinfection rate and vertical transmission in Brazil merits urgent attention and effective measures to reduce the transmission of HIV among spouses and sex partners.

Role of DC-SIGN and L-SIGN receptors in HIV-1 vertical transmission

The innate immune system acts in the first line of host defense against pathogens. One of the mechanisms used involves the early recognition and uptake of microbes by host professional phagocytes, through pattern recognition receptors (PRRs). These PRRs bind to conserved microbial ligands expressed by pathogens and initiate both innate and adaptative immune responses. Some PRRs located on the surface of dendritic cells (DCs) and other cells seem to play an important role in human immunodeficiency virus type 1 (HIV-1) transmission. Dendritic cell–specific intercellular adhesion molecule–3 grabbing non-integrin, CD209 (DC-SIGN) and its homolog, DC-SIGN-related (DC-SIGNR or L-SIGN) receptors are PPRs able to bind the HIV-1 gp120 envelope protein and, because alterations in their expression patterns also occur, they might play a role in both horizontal and vertical transmission as well as in disseminating the virus within the host. This review aims to explore the involvement of the DC-SIGN and L-SIGN receptors in HIV-1 transmission from mother to child.

Inhibition of DC‐SIGN‐mediated transmission of human immunodeficiency virus type 1 by Toll‐like receptor 3 signalling in breast milk macrophages

The majority of cells in early/colostrum milk are breast milk macrophages (BrMMø) expressing dendritic cell (DC)-specific intercellular adhesion molecule 3 (ICAM3) grabbing nonintegrin (DC-SIGN), and the expression level of DC-SIGN on BrMMø will determine cell-to-cell human immunodeficiency virus type 1 (HIV-1) transmissibility. Thus, one of the strategies to prevent vertical transmission of HIV-1 through breast-feeding is to find a way to suppress DC-SIGN expression on BrMMø. As for the expression of Toll-like receptors (TLRs) in BrMMø, TLR3 was always seen in BrMMø but not in peripheral blood monocytes (PBMo). Also, the expression of TLR3 was slightly enhanced in BrMMø when the cells were treated with interleukin (IL)-4. Moreover, when TLR3 was stimulated with its specific ligand, the double-stranded RNA (dsRNA) poly(I:C), DC-SIGN expression on BrMMø was reduced even in the IL-4-mediated enhanced state. Some reduction may be caused by type I interferons (IFNs), such as IFN-alpha/beta, secreted from BrMMø. Indeed, both IFNs, particularly IFN-beta, showed a strong capacity to suppress the enhancement of DC-SIGN expression on IL-4-treated BrMMø and such TLR3-mediated DC-SIGN suppression was partially abrogated by the addition of anti-IFN-alpha/beta-receptor-specific antibodies. As expected, DC-SIGN-mediated HIV-1 transmission to CD4-positive cells by BrMMø was inhibited by either poly(I:C) stimulation or by treatment with type I IFNs. These findings suggest a possible strategy for preventing mother-to-child transmission (MTCT) of HIV-1 via breast-feeding through TLR3 signalling.

Determinants and trends in perinatal human immunodeficiency virus type 1 (HIV-1) transmission in the metropolitan area of Belo Horizonte, Brazil: 1998 - 2005

Significant decrease in human immunodeficiency virus type 1 (HIV-1) vertical transmission has been observed worldwide in centers where interventions such as antiretroviral therapy (ART), elective cesarean section, and avoidance of breastfeeding have been implemented. This prospective cohort study aimed to assess the determinants of and the temporal trends in HIV-1 vertical transmission in the metropolitan area of Belo Horizonte, Brazil from January 1998 to December 2005. The rate of HIV-1 vertical transmission decreased from 20% in 1998 to 3% in 2005. This decline was associated with increased use of more complex ART regimens during pregnancy. Multivariate analysis restricted to clinical variables demonstrated that non ART, neonatal respiratory distress/sepsis and breastfeeding were independently associated with HIV-1 vertical transmission. When laboratory parameters were included in the model, high maternal viral load and non maternal ART were associated with HIV-1 vertical transmission. The results from this study confirm the impact of ART in the reduction of HIV-1 vertical transmission and indicate the need for improvement in the care and monitoring of mother and infant pairs affected by HIV-1.

The role of infant immune responses and genetic factors in preventing HIV-1 acquisition and disease progression.

Mother-to-child HIV-1 transmission accounts for more than 700 000 new paediatric HIV-1 infections in developing countries each year [1]. This comprises less than one-third of the infants born to human immunodeficiency virus type 1 (HIV-1) infected mothers, the majority of whom remain uninfected despite recurrent risk for contact with the virus in utero, during delivery and through breastfeeding. A comprehensive approach to studying infant immunity against HIV-1 may provide insight into the determinants of HIV-1 acquisition, promote an understanding of resistance to infection in the setting of repeated exposure to the virus and contribute to the development of therapeutic interventions or vaccines against HIV-1 transmission. Several unique features of mother-to-child HIV-1 transmission provide advantages in determining correlates of HIV-1 acquisition and viral immunity when compared to sexual HIV-1 transmission models. Both HIV-1 infected mothers and their exposed infants can be evaluated for viral and immunological factors associated with transmission. HIV-1 exposure can be characterized by quantifying maternal HIV-1 viral load in plasma, breast milk and genital tract secretions, and infant immune responses can be defined simultaneously or near the time of exposure. Timing of transmission can be estimated using HIV-1 polymerase chain reaction (PCR) at birth and at regular intervals after exposure during delivery and breastfeeding. Vertical HIV-1 transmission risk is also higher than sexual transmission risk. Per sexual act, it is estimated that the risk of heterosexual transmission is approximately 0·1% in an antiretroviral naive population [2]. The risk of HIV-1 acquisition during delivery ranges from 10 to 20%, more than 100-fold higher than heterosexual transmission rates. Disparities between heterosexual and vertical HIV-1 transmission rates persist in the setting of antiretroviral therapy. This enables mother–child transmission studies to provide robust epidemiological data regarding specific immune mechanisms and combinations of immune responses that may constitute protective immunity against HIV-1. This review examines the spectrum of innate, humoral and cellular immune responses and genetic factors that have been studied in infants who are HIV-1 infected or HIV-1 exposed and uninfected (Fig. 1). Fig. 1 Immune responses and genetic factors associated with mother-to-child HIV-1 transmission and paediatric HIV-1 disease progression. *May be maternally acquired in utero or via breast milk. †Alloimmunity is dependent on degree of maternal–infant ... INNATE IMMUNITY Innate immune responses are generated rapidly and are important in preventing and containing infections with a variety of viral pathogens. Broad innate immunity may also be capable of protecting against immune-escape viruses generated by more narrow adaptive immune responses. In HIV-1 transmission and disease progression, relevant innate mechanisms of immunity include the activity of natural killer (NK) cells and antiviral proteins such as the CC chemokines, CD8+ antiviral factor (CAF) and secretory leucocyte protease inhibitor (SLPI). Natural killer (NK) cell activity Natural killer (NK) cells induce inflammation and lyse infected cells without prior sensitization and in a non-HLA restricted manner. NK cells from HIV-1 infected individuals release the CC chemokines MIP-1α, MIP-1β and RANTES, three factors that have been shown to inhibit HIV-1 independently in vitro by blocking the CCR5 HIV-1 coreceptor [3,4]. NK cells also act by lysing HIV-1 infected cells via antibody-dependent cellular cytotoxicity (ADCC). This is initiated by binding of NK cell Fc receptors (CD16) to target cells coated with HIV-specific antibodies of the subclass IgG1 [5–7]. HIV-specific ADCC antibodies are directed against the viral envelope glycoproteins gp120 and gp41 and are distinct from virus-neutralizing antibodies [8]. There is conflicting evidence regarding the role of NK cells in containing HIV-1 in chronically infected children and in preventing vertical HIV-1 transmission. Several studies have evaluated HIV-specific ADCC antibody titres in sera of infants born to HIV-1 infected mothers and found that these antibodies are transferred efficiently across the placenta from mother to fetus [9,10]. However, there was no significant correlation between antibody titres at birth and either HIV-1 disease progression during 2 years of follow-up or mother-to-child HIV-1 transmission [9,10]. Active production of HIV-specific ADCC antibodies was observed in the majority of HIV-infected infants only after 12 months of age [10] and effector cells from HIV-1 infected children appear unable to generate NK cell-mediated cytotoxicity [11]. Thus, an immature immune system may account for the absence of ADCC-mediated NK protection against HIV-1 infection in neonates and young infants, despite adequate levels of passively transferred ADCC antibodies. This may contribute to rapid HIV-1 progression in children infected with HIV-1 early in life [10,11].

The Low Viral Production in Trophoblastic Cells Is Due to a High Endocytic Internalization of the Human Immunodeficiency Virus Type 1 and Can Be Overcome by the Pro-inflammatory Cytokines Tumor Necrosis Factor-α and Interleukin-1

Maternal-infant transmission of human immunodeficiency virus type-1 (HIV-1) is the primary cause of this retrovirus infection in neonates. Trophoblasts have been proposed to play a critical role in modulating virus spread to the fetus. This paper addresses the mechanism of HIV-1 biology in trophoblastic cells. The trophoblastic cell lines BeWo, JAR, and JEG-3 were infected with reporter HIV-1 particles pseudotyped with envelope glycoproteins from the vesicular stomatitis virus or various strains of HIV-1. We demonstrate that despite a high internalization process of HIV-1 and no block in viral production, HIV-1 established a limited infection of trophoblasts with the production of very few progeny viruses. The factor responsible for this restriction to virus replication in such a cellular microenvironment is that the intracellular p24 is concentrated predominantly in endosomal vesicles following HIV-1 entry. HIV-1 transcription and virus production of infectious particles were both augmented upon treatment of trophoblasts with tumor necrosis factor-alpha and interleukin-1. However, the amount of progeny virions released by trophoblasts infected with native HIV-1 virions was so low even in the presence of pro-inflammatory cytokines that a co-culture step with indicator cells was necessary to detect virus production. Collectively these data illustrate for the first time that the natural low permissiveness of trophoblasts to productive HIV-1 infection is because of a restriction in the mode of entry, and such a limitation can be overcome with physiologic doses of tumor necrosis factor-alpha and interleukin-1, which are both expressed by the placenta, in conjunction with cell-cell contact. Considering that there is a linear correlation between viral load and HIV-1 vertical transmission, the environment may thus contribute to the propagation of HIV-1 across the placenta.

Human immunodeficiency virus (HIV)-specific antibody in cervicovaginal lavage specimens obtained from women infected with HIV type 1.

To evaluate correlates of anti-human immunodeficiency virus (HIV) type 1 (HIV-1) immunoglobulin (Ig) in the genital tract, anti-HIV-gp120 IgA and IgG titers in cervicovaginal lavage specimens obtained from 104 HIV-1-infected women were measured by enzyme-linked immunosorbent assay. Overall, 24% and 94% of women had detectable anti-gp120 IgA and IgG, respectively. CD4 cell count correlated negatively with total IgA concentration (r=-0.301; P=.0027) and positively with specific IgA activity (anti-gp120 IgA titer/total IgA concentration, r=0.306; P=.0023). Women with bacterial vaginosis had 5-fold lower anti-gp120 IgG titer (P=.0042), 5-fold lower total IgG concentration (P< or =.0001), and 4-fold higher specific IgG activity (P=.0474) compared with women who did not have bacterial vaginosis. Enhanced understanding of correlates of mucosal immunity to HIV-1 may assist in the design of vaccine strategies or in the prevention of vertical transmission of HIV-1.

Combination antiretroviral therapy in 100 HIV-1-infected pregnant women.

In recent years, combination antiretroviral therapy has substantially improved the prognosis of human immunodeficiency virus type-1 (HIV-1) infection. However, at present, information regarding the effects of these regimens during pregnancy is limited. Side-effects, vertical transmission rate and neonatal outcome associated with different combination therapies were evaluated retrospectively in a consecutive series of 100 women who attended the II Department of Obstetrics and Gynecology for the management of HIV-1 infection in pregnancy. Antiretroviral treatment was initiated at a median of 16 weeks gestation with a range from pre-pregnancy until 31 weeks gestation. Twentythree women continued their pre-pregnancy therapy during the first trimester of gestation. Protease inhibitors were incorporated in 23 of the final therapeutic regimens. Twentyfive women did not receive zidovudine. Most women (97) delivered by Caesarean section and none breast-fed. Prematurity rate for the entire series was 19%. When women who actively used illicit drugs were excluded, only seven of 69 (10%) women were found to deliver prematurely. The use of protease inhibitors was limited by an elevated frequency of severe gastrointestinal disturbances. The rate of congenital malformations did not appear to differ significantly from that reported in the literature for the general population. Only one of 102 live newborns was found to be HIV-1-infected (1.0%, 95% confidence interval; 0.3-4.6%). The present findings confirm the remarkable efficacy of combination antiretroviral therapy, Caesarean section and refraining from breast-feeding in lowering the rate of vertical HIV-1 transmission. Moreover, they are suggestive that combination antiretroviral therapy may not be related to major neonatal toxicity. The necessity to discontinue the therapy during the first trimester of pregnancy and to systematically incorporate zidovudine into combination regimens is discussed.

Maternal antibodies to HIV-1 envelope domains: No correlation with HIV-1 vertical transmission in patients from Argentina.

The role of the maternal antibody response in relation to vertical human immunodeficiency virus type 1 (HIV-1) transmission was investigated in HIV-1-infected mothers from Argentina. Sera from 23 transmitting and 18 nontransmitting HIV-1-infected mothers were tested for the presence of antibodies to V3 loop gp120 peptides representing both Argentinian sequences and several well-characterized viral isolates from different geographic areas. Argentinian sera from transmitting mothers had significantly higher capacity to react with four of 14 V3 loop peptides tested than sera from nontransmitting mothers. Frequency of reactivity against the other peptides did not differ between the two maternal groups. Furthermore, no differences in antibody affinity were found between transmitting and nontransmitting mothers. Sera were also tested against overlapping peptides covering a neutralizing epitope of the HIV-1 MN gp41 (amino acids 648-677). Statistical analysis indicated that no correlation between anti-gp41 antibodies and vertical transmission exists. Although we used V3 loop peptides based on local HIV-1 sequences, our data showed that maternal antibodies to these peptides, as well as to gp41 peptides, are not correlated with protection against HIV-1 vertical transmission.

Lack of protection against vertical transmission of HIV-1 by interferons produced during pregnancy in a cohort from East African republic of Malawi.

Interferons (IFNs) associated with pregnancy were studied for their possible role in inhibition of vertical transmission of the human immunodeficiency virus type 1 (HIV-1). A study group was composed of 43 HIV-1-positive mothers, of whom 15 transmitted the virus to the offspring and 28 did not. The control group included 48 HIV-1-negative mother-infant pairs. The IFN-alpha was detected only sporadically in the maternal sera from the groups of transmitters (27%), nontransmitters (21%), and controls (19%). The average levels of IFN-alpha were low, 16.3 +/- 2.5 pg/ml, 21.4 +/- 9.9 pg/ml, and 21.3 +/- 9.4 pg/ml among the transmitters, nontransmitters, and control subjects, respectively. In the cord blood, IFN-alpha was detected only on two occasions among transmitters, and on a single occasion in the control group. IFN-beta was absent from both maternal and cord blood in the study group, and found to be present in one case in the control group simultaneously in the maternal and fetal sera. In the placentas, on the other hand, both type I and II IFNs were expressed universally in the villous trophoblast, and IFN-alpha and -beta in the stromal macrophages as well. In one case among transmitters, no IFNs were detected; nevertheless, no significant difference with respect to nontransmitters could be confirmed. Our data suggest that although the placental IFNs have an antiviral potential, they are not sufficient to suppress transmission of HIV from mother to infant.

Effect of immediate neonatal zidovudine on prevention of vertical transmission of human immunodeficiency virus type 1

Objectives: To describe the effects of various short zidovudine (ZDV) prophylactic regimens on vertical transmission of human immunodeficiency virus type 1 (HIV-1) infection, especially the effect of immediate neonatal ZDV prophylaxis. Materials and Methods: The study included children of HIV-1-infected mothers who were born at a teaching hospital in Bangkok. The ZDV prophylaxis regimens varied by time periods that included: (1) no ZDV (1991–1996); (2) antenatal oral ZDV, 250 mg given twice a day starting at 34 to 36 weeks' gestation and continued until labor (1995–1998); (3) antenatal oral ZDV plus immediate neonatal oral ZDV, 6 mg/0.6 mL/dose started within the first 2 hours after birth and continued at 6-hour intervals for 4 to 6 weeks (1997–1998); and (4) intrapartum intravenous ZDV given in addition to regimen 3 (1998–1999). Neonatal ZDV was administered within 2 hours after birth in 95% of the neonates. Results: In a cohort of 136 children born at least 9 months before the analysis date, the HIV-1 vertical infection rates were: (1) no ZDV, 11 of 48 (22.9%, 95% confidence interval [Cl] = 12.0–37.3); (2) late antenatal ZDV, 10 of 47 (21.3%, 95% Cl = 10.7–35.7); (3) late antenatal ZDV plus immediate neonatal ZDV, 0 of 28 (0%, 95% Cl = 0–12.3); (4) late antenatal, intrapartum intravenous ZDV, plus immediate neonatal ZDV, 0 of 13 (0%, 95% Cl = 0–24.7). An estimated 0% (95% Cl = 0–8.6) of the infants who received immediate neonatal ZDV with or without intrapartum ZDV were infected, as compared with 22.1% (95% Cl = 14.2–31.8 ) of those who received no ZDV or only late antenatal ZDV (P < 0.001). Conclusion: The results of this study suggests high protective effect of immediate administration of neonatal ZDV. Perinatal components of antiretroviral prophylaxis provided the best results for protecting against vertical HIV-1 transmission.

Influence of maternal CD4 levels on the predictive value of virus load over mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). Study Group for Vertical Transmission.

Forty-four anti-HIV seropositive pregnant women were enrolled in a study of maternal factors related to mother-to-infant human immunodeficiency virus type 1 (HIV-1) transmission. HIV-1 infection was documented in 11 of 45 infants (24.4%). Obstetric factors, maternal CD4 counts, and disease stage were not related to the risk of transmission. HIV-1 RNA levels at delivery were significantly higher in mothers who transmitted the infection (P = .024). A strong relationship between viral load and risk of transmission was observed in women with stage A1 (P= .006), but not in those with stages A2-A3. These results suggest that vertical transmission of HIV-1 is multifactorial and that viral load plays a major role in mothers with early-stage HIV-1 infection.

The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1--a meta-analysis of 15 prospective cohort studies.

To evaluate the relation between elective cesarean section and vertical transmission of human immunodeficiency virus type 1 (HIV-1), we performed a meta-analysis using data on individual patients from 15 prospective cohort studies. North American and European studies of at least 100 mother-child pairs were included in the meta-analysis. Uniform definitions of modes of delivery were used. Elective cesarean sections were defined as those performed before onset of labor and rupture of membranes. Multivariate logistic-regression analysis was used to adjust for other factors known to be associated with vertical transmission. The primary analysis included data on 8533 mother-child pairs. After adjustment for receipt of antiretroviral therapy, maternal stage of disease, and infant birth weight, the likelihood of vertical transmission of HIV-1 was decreased by approximately 50 percent with elective cesarean section, as compared with other modes of delivery (adjusted odds ratio, 0.43; 95 percent confidence interval, 0.33 to 0.56). The results were similar when the study population was limited to those with rupture of membranes shortly before delivery. The likelihood of transmission was reduced by approximately 87 percent with both elective cesarean section and receipt of antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, as compared with other modes of delivery and the absence of therapy (adjusted odds ratio, 0.13; 95 percent confidence interval, 0.09 to 0.19). Among mother-child pairs receiving antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, rates of vertical transmission were 2.0 percent among the 196 mothers who underwent elective cesarean section and 7.3 percent among the 1255 mothers with other modes of delivery. The results of this meta-analysis suggest that elective cesarean section reduces the risk of transmission of HIV-1 from mother to child independently of the effects of treatment with zidovudine.

Medical management of the pregnant woman infected with human immunodeficiency virus type 1 and her child

Heterosexual contact and intravenous drug use continue to result in new cases of human immunodeficiency virus type 1 (HIV-1) infection among adolescents and women of childbearing age. In North American and European surveys, 0.1% to 0.3% of childbearing women are infected with HIV; rates are 10 to 20 times higher in some inner-city areas. Timely, comprehensive, and well-coordinated care of the pregnant HIV-infected mother offers a unique opportunity to significantly influence two lives simultaneously. The mother can be offered therapeutic and prophylactic agents to treat her own infection, including antiretroviral therapy, which has been shown to markedly reduce the risk of vertical HIV-1 transmission. Recent advances in diagnostic virology now make it possible to definitively identify by 3 to 4 months of age those infants who are infected with HIV. Infants infected with HIV can be offered effective prophylaxis against Pneumocystis carinii pneumonia, which has dramatically reduced the incidence of this once common infection. Infected infants also should be monitored closely to institute antiretroviral therapy, and to diagnose and treat opportunistic and intercurrent infections and other acquired immunodeficiency syndrome-defining illnesses in a timely way.

Breastfeeding and vertical transmission of HIV-1.

An estimated one-third to one-half of vertical transmission of human immunodeficiency virus type 1 (HIV-1) worldwide is due to breastfeeding. The exact frequency of breast milk HIV-1 transmission is unknown, but it has been estimated to be 14% in the setting of established maternal HIV-1 infection and 29% in the setting of acute maternal infection. The timing of breast milk transmission during the course of lactation also remains unknown, but two studies have found an association between duration of breastfeeding and risk of infant infection. In one such study, prolonged breastfeeding for 15 months or longer was associated with a twofold increased transmission risk. Human immunodeficiency virus type 1 DNA can be detected in over 50% of breast milk samples and is correlated with CD4 depletion and vitamin A deficiency. The presence of breast milk HIV-1 provirus is associated with increased transmission risk. Many current intervention strategies to prevent vertical transmission of HIV-1 are aimed at in utero or perinatal transmission. In developing countries in which breastfeeding by HIV-1 infected women is recommended practice, additional intervention strategies to reduce breast milk transmission warrant evaluation.

Sexual behavior and injection drug use during pregnancy and vertical transmission of HIV-1.

We evaluated maternal sexual behavior and injection drug use practices as possible risk factors for vertical transmission of human immunodeficiency virus type 1 (HIV-1). Data were analyzed from the Mothers and Infants Cohort Study, a prospective study in Brooklyn and the Bronx, New York. A total of 207 mother-infant sets were enrolled between 1986 and 1991 and followed for up to 4 years after the enrollment visit during pregnancy. HIV-1 transmission occurred in 49 of 201 mother-infant sets, yielding an overall transmission rate of 24.4% (95% confidence interval (CI) = 18.7% to 31.0%). Increased frequency of vaginal intercourse after the first trimester of pregnancy was positively associated with vertical transmission of HIV-1 (trend p = 0.03). A lifetime history of injection drug use was not associated with vertical transmission. However, a history of combined cocaine and heroin injection after the first trimester of pregnancy was associated with vertical HIV-1 transmission, particularly among women with CD4+ lymphocyte levels of 20% or higher (risk ratio = 4.0; 95% CI = 2.0 to 8.1). Cocaine and heroin injection drug use after the first trimester accounted for most of the relation between preterm birth and vertical HIV-1 transmission in this cohort. Maternal coinfection with hepatitis C virus or human T-cell lymphotropic virus types I and II could not explain these observations, because coinfection with these viruses had no detectable effect on HIV-1 transmission. These results suggest that maternal sexual behavior and injection drug use practices during the second and third trimester of pregnancy may modify the risk of vertical HIV-1 transmission.

Vertical transmission of human immunodeficiency virus type 1: seroreactivity by maternal antibodies to the carboxy region of the gp41 envelope glycoprotein.

Maternal antibodies against the envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) have previously been suggested to be important in influencing the rate of vertical transmission. In this study, serum antibody responses in mothers who did or did not transmit HIV-1 infection to their children were measured against the carboxy region of the transmembrane envelope glycoprotein gp41. Results indicate significantly higher binding reactivity of nontransmitter mothers compared with transmitters to three peptides spanning amino acids 771-810 and 841-856. In addition, high neutralization titers in maternal sera against HIV-1(MN) were associated with a nontransmission status. This is the initial report demonstrating a correlation between maternal antibody binding to epitopes within the carboxy region of gp41 envelope glycoprotein and lack of vertical transmission. Immunodetection that identifies antibodies to these regions in gp41 could therefore be considered a strategy to assess the risk of vertical transmission of HIV-1.

Genital shedding of human immunodeficiency virus type 1 DNA during pregnancy: association with immunosuppression, abnormal cervical or vaginal discharge, and severe vitamin A deficiency.

The presence of human immunodeficiency virus type 1 (HIV-1) in genital secretions may be a determinant of vertical HIV-1 transmission. Cervical and vaginal secretions from HIV-1-seropositive pregnant women were evaluated to determine prevalence and correlates of HIV-1-infected cells in the genital tract. HIV-1 DNA was detected by polymerase chain reaction in 32% of 212 cervical and 10% of 215 vaginal specimens. Presence of HIV-1 DNA in the cervix was associated with cervical mucopus and a significantly lower absolute CD4 cell count (354 vs. 469, P < .001). An absolute CD4 cell count <200 was associated with a 9.6-fold increased odds of cervical HIV-1 DNA detection compared with a count > or = 500 (95% confidence interval, 2.8-34.2). Detection of vaginal HIV- 1 DNA was associated with abnormal vaginal discharge, lower absolute CD4 cell count, and severe vitamin A deficiency. Presence of HIV-1-infected cells in genital secretions was associated with immunosuppression and abnormal cervical or vaginal discharge.