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.     

Perinatal transmission of major, minor, and multiple maternal human immunodeficiency virus type 1 variants in utero and intrapartum

Previous studies have provided conflicting data on the presence of selective pressures in the transmission of a homogeneous maternal viral subpopulation to the infant. Therefore, the purpose of this study was to definitively characterize the human immunodeficiency virus type 1 (HIV-1) quasispecies transmitted in utero and intrapartum. HIV-1 envelope gene diversity from peripheral blood mononuclear cells and plasma was measured during gestation and at delivery in mothers who did and did not transmit HIV perinatally by using a DNA heteroduplex mobility assay. Children were defined as infected in utero or intrapartum based on the timing of the first detection of HIV. Untreated transmitting mothers (n = 19) had significantly lower HIV-1 quasispecies diversity at delivery than untreated nontransmittting mothers (n = 18) (median Shannon entropy, 0.711 [0.642 to 0.816] versus 0.853 [0.762 to 0.925], P = 0.005). Eight mothers transmitted a single major env variant to their infants in utero, and one mother transmitted a single major env variant intrapartum. Four mothers transmitted multiple HIV-1 env variants to their infants in utero, and two mothers transmitted multiple env variants intrapartum. The remaining six intrapartum- and two in utero-infected infants had a homogeneous HIV-1 env quasispecies which did not comigrate with their mothers' bands at their first positive time point. In conclusion, in utero transmitters were more likely to transmit single or multiple major maternal viral variants. In contrast, intrapartum transmitters were more likely to transmit minor HIV-1 variants. These data indicate that different selective pressures, depending on the timing of transmission, may be involved in determining the pattern of maternal HIV-1 variant transmission.     

Mother-to-infant transmission of human immunodeficiency virus type 1 involving five envelope sequence subtypes.

Genetic analysis of human immunodeficiency virus type 1 (HIV-1) from cases of mother-to-infant transmission were analyzed in an effort to provide insights into the viral selection that may occur during transmission, as well as the timing and source of transmitted viruses. HIV-1 env genes obtained from seven mothers and their perinatally infected infants in Sweden were studied. Five envelope sequence clades (A to E) were found to be represented. We used a heteroduplex tracking assay (HTA) to assess the genetic relatedness between early viral isolates from the infants and serial maternal virus populations taken during pregnancy and at delivery. HTA findings were used to select for DNA sequence analysis maternal virus populations that were either closely or more distantly related to the infant virus. In each case, nucleotide sequence analysis confirmed the genetic relationships inferred by the HTA. Only maternal peripheral blood was sampled, and large sets of maternal specimens throughout pregnancy were generally not available. However, no consistent correlation was found to support the hypothesis that infant viruses should match blood-derived maternal virus genotypes found early in pregnancy if infants were found to be infected at birth or, conversely, that infant viruses should match blood-derived maternal virus genotypes found at delivery if infants were found to be infected only some time later.     

Role of maternal autologous neutralizing antibody in selective perinatal transmission of human immunodeficiency virus type 1 escape variants

Perinatal human immunodeficiency virus type 1 (HIV-1) transmission is characterized by acquisition of a homogeneous viral quasispecies, yet the selective factors responsible for this genetic bottleneck are unclear. We examined the role of maternal autologous neutralizing antibody (aNAB) in selective transmission of HIV-1 escape variants to infants. Maternal sera from 38 infected mothers at the time of delivery were assayed for autologous neutralizing antibody activity against maternal time-of-delivery HIV-1 isolates in vitro. Maternal sera were also tested for cross-neutralization of infected-infant-first-positive-time-point viral isolates. Heteroduplex and DNA sequence analyses were then performed to identify the initial infecting virus as a neutralization-sensitive or escape HIV-1 variant. In utero transmitters (n = 14) were significantly less likely to have aNAB to their own HIV-1 strains at delivery than nontransmitting mothers (n = 17, 14.3% versus 76.5%, P = 0.003). Cross-neutralization assays of infected-infant-first-positive-time-point HIV-1 isolates indicated that while 14/21 HIV-1-infected infant first positive time point isolates were resistant to their own mother's aNAB, no infant isolate was inherently resistant to antibody neutralization by all sera tested. Furthermore, both heteroduplex (n = 21) and phylogenetic (n = 9) analyses showed that selective perinatal transmission and/or outgrowth of maternal autologous neutralization escape HIV-1 variants occurs in utero and intrapartum. These data indicate that maternal autologous neutralizing antibody can exert powerful protective and selective effects in perinatal HIV-1 transmission and therefore has important implications for vaccine development.     

Neutralizing Antibody Escape during HIV-1 Mother-to-Child Transmission Involves Conformational Masking of Distal Epitopes in Envelope

HIV-1 variants transmitted to infants are often resistant to maternal neutralizing antibodies (NAbs), suggesting that they have escaped maternal NAb pressure. To define the molecular basis of NAb escape that contributes to selection of transmitted variants, we analyzed 5 viruses from 2 mother-to-child transmission pairs, in which the infant virus, but not the maternal virus, was resistant to neutralization by maternal plasma near transmission. We generated chimeric viruses between maternal and infant envelope clones obtained near transmission and examined neutralization by maternal plasma. The molecular determinants of NAb escape were distinct, even when comparing two maternal variants to the transmitted infant virus within one pair, in which insertions in V4 of gp120 and substitutions in HR2 of gp41 conferred neutralization resistance. In another pair, deletions and substitutions in V1 to V3 conferred resistance, but neither V1/V2 nor V3 alone was sufficient. Although the sequence determinants of escape were distinct, all of them involved modifications of potential N-linked glycosylation sites. None of the regions that mediated escape were major linear targets of maternal NAbs because corresponding peptides failed to compete for neutralization. Instead, these regions disrupted multiple distal epitopes targeted by HIV-1-specific monoclonal antibodies, suggesting that escape from maternal NAbs occurred through conformational masking of distal epitopes. This strategy likely allows HIV-1 to utilize relatively limited changes in the envelope to preserve the ability to infect a new host while simultaneously evading multiple NAb specificities present in maternal plasma.     

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.     

Mutations that confer resistance to broadly-neutralizing antibodies define HIV-1 variants of transmitting mothers from that of non-transmitting mothers

Despite considerable reduction of mother-to-child transmission (MTCT) of HIV through use of maternal and infant antiretroviral therapy (ART), over 150,000 infants continue to become infected with HIV annually, falling far short of the World Health Organization goal of reaching <20,000 annual pediatric HIV cases worldwide by 2020. Prior to the widespread use of ART in the setting of pregnancy, over half of infants born to HIV-infected mothers were protected against HIV acquisition. Yet, the role of maternal immune factors in this protection against vertical transmission is still unclear, hampering the development of synergistic strategies to further reduce MTCT. It has been established that infant transmitted/founder (T/F) viruses are often resistant to maternal plasma, yet it is unknown if the neutralization resistance profile of circulating viruses predicts the maternal risk of transmission to her infant. In this study, we amplified HIV-1 envelope genes (env) by single genome amplification and produced representative Env variants from plasma of 19 non-transmitting mothers from the U.S. Women Infant Transmission Study (WITS), enrolled in the pre-ART era. Maternal HIV Env variants from non-transmitting mothers had similar sensitivity to autologous plasma as observed for non-transmitting variants from transmitting mothers. In contrast, infant variants were on average 30% less sensitive to paired plasma neutralization compared to non-transmitted maternal variants from both transmitting and non-transmitting mothers (p = 0.015). Importantly, a signature sequence analysis revealed that motifs enriched in env sequences from transmitting mothers were associated with broadly neutralizing antibody (bnAb) resistance. Altogether, our findings suggest that circulating maternal virus resistance to bnAb-mediated neutralization, but not autologous plasma neutralization, near the time of delivery, predicts increased MTCT risk. These results caution that enhancement of maternal plasma neutralization through passive or active vaccination during pregnancy may potentially drive the evolution of variants fit for vertical transmission.     

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.     

Genetic analysis of simian immunodeficiency virus expressed in milk and selectively transmitted through breastfeeding

To develop effective intervention strategies that prevent breast milk transmission of human immunodeficiency virus (HIV), we must understand the specific viral properties and mechanisms responsible for infant infection. We have used lactating rhesus macaques infected with a pathogenic simian immunodeficiency virus (SIV) stock to analyze the viral genotypes expressed in plasma and milk throughout the disease course and to identify those variants ultimately transmitted to infants through breastfeeding. In these studies we observed mother-to-infant transmission of SIV/Delta(B670) by eight females during the chronic phase of disease, and we analyzed by heteroduplex tracking assays and sequence analysis the distribution and fluctuations in viral genotypes expressed. Each female expressed multiple V1 envelope genotypes in milk near the time of transmission, while a single genotype was found in each of the infants. Variants transmitted to infants were not expressed throughout the maternal disease course but were only detected near the time of transmission. The emergence of the transmitted genotype in the dam typically occurred in plasma before milk and was coincident with increased milk viral loads. Transmitted genotypes tended to be longer and more glycosylated and had a less negative charge over the V1 region compared to viral genotypes expressed in milk but not transmitted. These observations demonstrate that specific viral genotypes are selectively transmitted to infants through breastfeeding and support the hypothesis that transmission occurs as genotypes adapt for efficient expression in milk.     

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.     

HIV-1-specific CD8+ T cell responses and viral evolution in women and infants

CD8+ T lymphocyte responses play an important role in controlling HIV-1 replication but escape from CD8+ T cell surveillance may limit the effectiveness of these responses. Mother-to-child transmission of CD8+ T cell escape variants may particularly affect CD8+ T cell recognition of infant HIV-1 epitopes. In this study, amino acid sequence variation in HIV-1 gag and nef was examined in five untreated mother-infant pairs to evaluate the potential role of CD8+ T cell responses in the evolution of the viral quasispecies. Several CD8+ T cell escape variants were detected in maternal plasma. Evaluation of infant plasma viruses at 1-3 mo documented heterogeneity of gag and nef gene sequences and mother-to-child transmission of CD8+ T cell escape variants. Infant HLA haplotype and viral fitness appeared to determine the stability of the escape mutants in the infant over time. Changes in CD8+ T cell epitope sequences were detected in infants' sequential plasma specimens, suggesting that infants are capable of generating virus-specific CD8+ T cell responses that exert selective pressures in vivo. Altogether, these studies document that HIV-1-specific CD8+ T cell responses contribute to the evolution of the viral quasispecies in HIV-1-infected women and their infants and may have important implications for vaccine design.     

海南省及云南西双版纳州HIV-1的分子流行病学比较研究

目的调查比较HIV-1在海南省及云南西双版纳州的流行情况及分子流行病学分析高危因素传播的情况以及传播链的鉴定。方法我们与海南省CDC及西双版纳州CDC合作在其境内开展了HIV血清学调查,筛查了海南省（1991～2006）及西双版纳州（1996～2005）高危人群志愿者血清样本。在本次两地调查中,我们通过系统进化分析方法,对已诊断的HIV感染者进行分子流行病学的追踪,来分析其中的主要流行亚群以及结合个案追踪进行传播链的鉴定。结果我们共筛查了海南省499725人,共检出HIV阳性感染者523例（0.1%）,以注射器吸毒感染为主要传播途径（经共用注射器吸毒感染占69．2％、经性接触传播占19．3％、供血和使用血液／血液制品感染占3．3％、母婴传播占0．8％、不详占7．7％）。然而,在西双版纳州筛查中发现了较海南省高20倍的检出率：在25390受检人中,共检出HIV阳性感染者501例（2％）并以异性性传播为主（经异性性接触传播占77．3％、经共用注射器吸毒感染占21．1％、经同性性接触传播占0．4％、母婴传播占1．2％）。在海南省抽样的83人中,以CRF01_-AE重组亚型（70人,84．3％）为主要病毒亚型,其他病毒亚型包括B’亚型（8人）、C亚型（2人）、CRF08_BC重组亚型（1人）、B亚型（1人）和1个未报道过的CRF01～AE／B’重组亚型。同样,在版纳抽样的44人中,也以CRF01_AE重组亚型（27人,61．3％）为主要病毒亚型,其他病毒亚型包括CRF08_BC重组亚型（15人）、G亚型（1人）、和1个未报道过的B／C重组亚型。在海南省抽样中有66人（79．5％）分布于4个大小不同的传播群,传播群1（59人）较大（奠基效应）,属于CRF01_AE重组亚型,传播群2、3、4则较小,分别为3、2、2人,分别属于CRF01_AE重组亚型、C亚型和B’亚型。相反,在版纳抽样中有18人（40．9％）分布于8个较小的传播群（每群平均含2．25感染个体）。在海南省抽样中怀疑的6对异性性接触的传播链中,经系统进化分析方法确认了其中的4对,2对被拒绝。在版纳抽样中怀疑的8对异性性接触的传播链中,经系统进化分析方法确认了其中的5对,2对被拒绝,1对无法分析,此外还新发现了3对异性性接触传播群。结论HIV-1感染者的分子流行病学的追踪和分析对于追溯艾滋病流行的源头和地区性预防策略的制定有着重大的意义。     

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...     

Molecular Evidence for Mother-to-Child Transmission of Multiple Variants by Analysis of RNA and DNA Sequences of Human Immunodeficiency Virus Type 1

We have examined the viral selection that may occur during transmission by studying the env gene sequences from four cases of mother-to-child transmission of human immunodeficiency virus type 1. The V3 region sequences were directly amplified from both plasma viral RNA and peripheral blood mononuclear cells containing proviral DNA from mothers at delivery and at the time of diagnosis for children. Transmission occurred perinatally in three cases. The similarity of the viral sequences in each infant sample contrasted with the heterogeneous viral populations in the mothers. Phylogenetic analysis indicated the transmission of one or a few closely related maternal minor virus variants. In contrast, the child virus population in the fourth case was as heterogeneous as that of his mother, and phylogenetic analysis strongly suggested the transmission of multiple maternal variants. This case of multiple transmission was confirmed by analyzing sequences obtained at three times after delivery. Strains with sequences corresponding to the syncytium-inducing phenotype were also transmitted in this fourth case, and this was associated with the rapid development of disease in the child. There was no evidence for transmission of particular viral variants from mother to infant. We have thus described a particular case of vertical human immunodeficiency virus type 1 transmission with the transmission of multiple maternal variants to the infant and a rapid, fatal outcome in the child.     

Neutralization escape variants of human immunodeficiency virus type 1 are transmitted from mother to infant

Maternal passive immunity typically plays a critical role in protecting infants from new infections; however, the specific contribution of neutralizing antibodies in limiting mother-to-child transmission of human immunodeficiency virus type 1 is unclear. By examining cloned envelope variants from 12 transmission pairs, we found that vertically transmitted variants were more resistant to neutralization by maternal plasma than were maternal viral variants near the time of transmission. The vertically transmitted envelope variants were poorly neutralized by monoclonal antibodies b12 [corrected] 2G12, 2F5, and 4E10 individually or in combination. Despite the fact that the infant viruses were among the most neutralization resistant in the mother, they had relatively few glycosylation sites. Moreover, the transmitted variants elicited de novo neutralizing antibodies in the infants, indicating that they were not inherently difficult to neutralize. The neutralization resistance of vertically transmitted viruses is in contrast to the relative neutralization sensitivity of viruses sexually transmitted within discordant couples, suggesting that the antigenic properties of viruses that are favored for transmission may differ depending upon mode of transmission.     

Restricted Genetic Diversity of HIV-1 Subtype C Envelope Glycoprotein from Perinatally Infected Zambian Infants

Background

Mother-to-child transmission of HIV-1 remains a significant problem in the resource-constrained settings where anti-retroviral therapy is still not widely available. Understanding the earliest events during HIV-1 transmission and characterizing the newly transmitted or founder virus is central to intervention efforts. In this study, we analyzed the viral env quasispecies of six mother-infant transmission pairs (MIPs) and characterized the genetic features of envelope glycoprotein that could influence HIV-1 subtype C perinatal transmission.

Methodology and Findings

The V1-V5 region of env was amplified from 6 MIPs baseline samples and 334 DNA sequences in total were analyzed. A comparison of the viral population derived from the mother and infant revealed a severe genetic bottleneck occurring during perinatal transmission, which was characterized by low sequence diversity in the infant. Phylogenetic analysis indicates that most likely in all our infant subjects a single founder virus was responsible for establishing infection. Furthermore, the newly transmitted viruses from the infant had significantly fewer potential N-linked glycosylation sites in Env V1-V5 region and showed a propensity to encode shorter variable loops compared to the nontransmitted viruses. In addition, a similar intensity of selection was seen between mothers and infants with a higher rate of synonymous (dS) compared to nonsynonymous (dN) substitutions evident (dN/dS<1).

Conclusions

Our results indicate that a strong genetic bottleneck occurs during perinatal transmission of HIV-1 subtype C. This is evident through population diversity and phylogenetic patterns where a single viral variant appears to be responsible for infection in the infants. As a result the newly transmitted viruses are less diverse and harbored significantly less glycosylated envelope. This suggests that viruses with the restricted glycosylation in envelope glycoprotein appeared to be preferentially transmitted during HIV-1 subtype C perinatal transmission. In addition, our findings also indicated that purifying selection appears to predominate in shaping the early intrahost evolution of HIV-1 subtype C envelope sequences.     

Differences in natural killer cell quantification and receptor profile expression in HIV-1 infected Chinese children

Natural killer (NK) cells are believed to play a role in the progression of human immunodeficiency virus 1 (HIV-1) disease, and NK cell levels are reduced in individuals with chronic HIV-1 infection. To assess the effects on quantity of NK cells and the changes of NK cell receptors in HIV-1 infected children via mother-to-child transmission, the percentage of NK cells is quantified and the changes in the NK cell receptor profiles in 20 HIV-1 infected children who are not progressing into AIDS were examined. The results showed that NK cell percentage was decreased in the HIV-1 infected children. The expression of NKp30 on NK cells was increased, while the expressions of CD16, NKp44, NKp46, NKp80, NTB-A, CD244, KIR2D, KIR3DL1 and NKG2D on NK cells were decreased in the HIV-1 infected children. NK cell cytolytic activity was elevated in HIV-1 infected children. These results indicate that the acute changes in NK cell percentage and NK cell receptors in HIV-1 infected children are different from the HIV-1 infected adult individuals. Moreover, serum concentrations of IL-18 were elevated in HIV-infected children compared to HIV-uninfected controls. These differences probably play a role in protecting against transmission of maternal HIV-1 virus and guiding the therapeutic strategies for HIV-1 infected children.     

Retrospective study of maternal HIV-1 and HIV-2 infections and child survival in Abidjan,C?te d'Ivoire.

OBJECTIVES--To compare the effects of maternal HIV-1 and HIV-2 infections on outcome of pregnancy, infant mortality, and child survival, and to measure serological concordance between mothers and children. DESIGN--Retrospective cohort study with cross sectional study of concordance for HIV antibodies. SETTING--Hospital, tuberculosis clinic, and maternal and child health centre in Abidjan, Côte d''Ivoire, west Africa. SUBJECTS--986 women who had had a total of 2758 pregnancies since 1980. The last born children of 194 of these women. MAIN OUTCOME MEASURES--Pregnancy outcomes; mortality for all children born since 1980; and outcome for last born children. Serological concordance between mothers and last born children. RESULTS--Women with HIV-1 and HIV-2 infections had higher rates of spontaneous abortion and stillbirth than uninfected women (86/769 in HIV-1 positive women, 48/421 in HIV-2 positive, 31/234 in dually reactive, and 96/1131 in uninfected). Compared with children born to uninfected mothers (mortality 10.3%), greater proportions of children of HIV-1 positive (20.6%) and dually reactive (20.3%) mothers had died; mortality in children of HIV-2 infected women (13.1%) was not significantly increased. Infant mortalities for the last born children of HIV-1 positive, dually reactive, HIV-2 positive, and seronegative women were, respectively, 133, 82, 32, and 40 per 1000 live births. Nine of 77 last born children of HIV-1 positive mothers were concordantly seropositive compared with none of 21 children of HIV-2 infected mothers. CONCLUSIONS--Maternal HIV-2 infection has less influence on child survival than infection with HIV-1, probably because of a lower vertical transmission rate.