Placental malaria and perinatal transmission of human immunodeficiency virus type 1

Prevalence of placental malaria in human immunodeficiency virus (HIV) type 1-infected and -uninfected women and the effect of placental malaria on genital shedding and perinatal transmission of HIV-1 were examined. Genital samples for HIV-1 DNA RNA were collected during labor. Infants were tested for HIV-1 at 1 day and 6 weeks postpartum. Placental malaria was diagnosed by histopathological examination: 372 placentas of HIV-1-infected women and 277 of HIV-1-uninfected women were processed. A higher prevalence of placental malaria was seen in HIV-1-infected women. No association was found between placental malaria and either maternal virus load, genital HIV-1 DNA, or HIV-1 RNA. Placental malaria did not correlate with in utero or peripartal transmission of HIV-1.     

Thyroid function in children with perinatal human immunodeficiency virus type 1 infection.

OBJECTIVE: To study thyroid function in children with perinatal HIV-1 infection retrospectively and determine whether thyroid abnormalities are correlated with clinical condition, disease progression, immunological impairment, and viral load. STUDY DESIGN AND SETTING: Total (TT4) and free (FT4) thyroxine, total (TT3) and free (FT3) triiodothyronine, reverse triiodothyronine (rT3), thyrotropin (TSH), thyroglobulin (TG), and thyroid binding globulin (TBG) were measured twice in 56 children with perinatal human immunodeficiency virus type 1 (HIV-1) infection. Median age at first determination was 13.5 (range: 0.03-127.0) months; median age at second determination was 66.2 (range 3.42-147.4) months. Antithyroglobulin, antimicrosomal, thyroid peroxidase, and thyrotropin receptor antibodies were also evaluated. Fifty-three healthy children were selected as controls. RESULTS: TT3, TT4, FT4, and TG were significantly reduced and rT3, TBG, and TSH increased in children with HIV-1 infection when compared with controls. Thyroid dysfunction correlated with severe immunosuppression and high viral load early in life preceded the onset of the disease and worsened over time. Autoantibodies were negative in all children with HIV-1 infection in all determinations. CONCLUSION: Thyroid abnormalities are observed early in the course of perinatal HIV-1 infection; thyroid dysfunction is particularly pronounced in children with severe immunosuppression and high viral load. Modifications of thyroid function precede worsening of clinical course in HIV-1 infected children.     

Lack of association between human immunodeficiency virus type 1 antibody in cervicovaginal lavage fluid and plasma and perinatal transmission, in Thailand

To determine the association between human immunodeficiency virus type 1 (HIV)-specific antibody and RNA levels in cervicovaginal lavage (CVL) samples and plasma, zidovudine treatment, and perinatal transmission, HIV subtype E gp160-specific IgG and IgA were serially measured in a subset of 74 HIV-infected women in a placebo-controlled trial of zidovudine, beginning at 36 weeks of gestation. HIV IgG was detected in 100% of plasma and 97% of CVL samples; HIV IgA was consistently detected in 62% of plasma and 31% of CVL samples. Antibody titers in CVL samples correlated better with the RNA level in CVL samples than with plasma antibody titers. Zidovudine did not affect antibody titers. Perinatal HIV transmission was not associated with antibody in CVL samples or plasma. HIV-specific antibody is present in the cervicovaginal canal of HIV-infected pregnant women; its correlation with the RNA level in CVL fluid suggests local antibody production. However, there was no evidence that these antibodies protected against perinatal HIV transmission.     

Comparative prediction of perinatal human immunodeficiency virus type 1 transmission,using multiple virus load markers

Maternal plasma human immunodeficiency virus (HIV) type 1 RNA load has a role in perinatal transmission, but significant overlap in the range of plasma virus loads among transmitters and nontransmitters is often observed, which makes it difficult to predict transmission outcome. We measured several virus markers in a drug-naive population of HIV-1-infected mothers in Botswana. Maternal plasma HIV-1 RNA load, peripheral blood mononuclear cell-associated blood HIV-1 DNA load, and cervicovaginal fluid (CVF) HIV-1 DNA load were determined using quantitative real-time polymerase chain reaction. The overall rate of transmission among these mother-infant pairs was 35.7%. Median infant age was 2.5 months. An association between increased plasma HIV-1 RNA load and perinatal transmission was observed (odds ratio [OR], 2.20/1-log virus load; 95% confidence interval [CI], 1.15-4.18). However, the association between increased blood HIV-1 DNA load and perinatal transmission was stronger (OR, 10.30; 95% CI, 2.11-50.38). When blood HIV-1 DNA load was combined with CVF HIV-1 DNA load, the association with transmission increased (OR, 25.0; 95% CI 2.73-228.60).     

Diarrheal disease in patients infected with human immunodeficiency virus in Bangkok, Thailand.

Diarrheal disease and its associated morbidities occur frequently in patients infected with human immunodeficiency virus (HIV) and may be associated with a decreased quality of life. We studied the spectrum of symptoms, measures of nutritional status, and the enteric pathogens associated with diarrheal disease in a group of 24 patients infected with HIV in Bangkok, Thailand compared with a group of 19 patients infected with HIV without diarrhea cared for at the same clinic. Patients with diarrhea appeared to have more advanced disease by CD4 cell counts and complained more frequently of symptoms such as anorexia, gas, and bloating than patients without diarrhea. Patients with diarrhea had a tendency toward a lower nutritional status, as measured by body mass index and mid arm circumference. Stool culture and examination revealed that enteric pathogens including Salmonella species and Cryptosporidium parvum sporidia were recovered at equal frequencies in patients with and without diarrhea (27% of the patients with diarrhea and 25% of the patients without diarrhea). Microsporidia was identified in one patient with diarrhea. It was not possible to identify a pathogen in 73% of the patients with diarrhea and 75% of the patients without diarrhea, suggesting that additional agents or factors may be responsible for the diarrheal symptoms in the patients with diarrhea. More extensive studies to identify potentially treatable pathogens in HIV-infected patients with diarrhea in Thailand are warranted and further attempts to better define the syndrome of pathogen-negative diarrheal disease in patients infected with HIV might result in the development of more targeted interventions in these patients.     

Secretory leukocyte protease inhibitor in vaginal fluids and perinatal human immunodeficiency virus type 1 transmission

The presence of both viral particles and antiviral mucosal proteins may represent critical determinants of perinatal human immunodeficiency virus type 1 (HIV-1) transmission. In 60 HIV-1-infected women, concentrations of the innate mucosal protein, secretory leukocyte protease inhibitor (SLPI), were lower in vaginal fluid samples from 17 women whose babies became infected than in samples from nontransmitting women (mean+/-SE, 57+/-11 vs. 557+/-177 ng/mL, respectively; P=.01). Rates of transmission among women with higher SLPI concentrations (>100 ng/mL) were lower than those among women with lower concentrations (<100 ng/mL; 8.7% vs. 40.5%, respectively; P=.01). Concentrations of other putative HIV-1-inhibitory innate immune factors were similar in both groups. Concentrations of vaginal HIV-1 tended to be higher in transmitting than in nontransmitting women (407 vs. 174 virions/mL; P=.09). Increased concentrations of selected innate mucosal immune factors, such as SLPI, seem to be associated with reduced rates of perinatal HIV-1 transmission and may contribute to natural antiretroviral defense.     

Severe transient neutropenia associated with acute human immunodeficiency virus type 1 infection

Severe neutropenia associated with primary HIV infection is unusual. We report the fifth case in a 50-year-old male with a neutrophil count of 500/mm(3) and a platelet count of 92,000/mm(3) at the time of early HIV-1 seroconversion. In all previously published cases and in our case, severe neutropenia was a very early sign of acute HIV infection, and it regressed spontaneously and quickly. HIV testing should be recommended when severe neutropenia is observed, especially in the context of a flu-like or mononucleosis-like infectious syndrome.     

The HLA A2/6802 supertype is associated with reduced risk of perinatal human immunodeficiency virus type 1 transmission

Certain HLAs may, in part, account for differences in human immunodeficiency virus type 1 (HIV-1) susceptibility by presenting conserved immunogenic epitopes for T cell recognition. The HLA supertype A2/6802 is associated with decreased susceptibility to HIV-1 among sex workers. The alleles in this supertype present the same HIV-1 peptide epitopes for T cell recognition in some cases. This study sought to determine whether the HLA A2/6802 supertype influenced HIV-1 transmission in a prospective cohort of HIV-1-infected mothers and children in Kenya. Decreased perinatal HIV-1 infection risk was strongly associated with possession of a functional cluster of related HLA alleles, called the A2/6802 supertype (odds ratio, 0.12; 95% confidence interval, 0.03-0.54; P=.006). This effect was independent of the protective effect of maternal-child HLA discordance. These data provide further evidence that HLA supertypes are associated with differential susceptibility to HIV-1 transmission.     

Thrombotic thrombocytopenic purpura associated with human immunodeficiency virus type 1 (HIV-1) infection

The cases of 14 patients with thrombotic thrombocytopenic purpura admitted to one institution after 1980 were reviewed. Three of the fourteen cases occurred in patients with the acquired immunodeficiency syndrome (AIDS)-related complex and one occurred in a patient with probable human immunodeficiency virus (HIV) infection. The diagnosis in all four cases had been made after 1985. The association of thrombotic thrombocytopenic purpura with HIV infection was judged to be statistically significant on the basis of the proportion of patients with AIDS among the general population of patients admitted to the same institution during the same period. The fact that this association is only now being recognized suggests that there may be a long incubation period for thrombotic thrombocytopenic purpura or that the association is a rare one recognized now only because of the increased number of persons with AIDS.     

Higher seroprevalence of Entamoeba histolytica infection is associated with human immunodeficiency virus type 1 infection in Taiwan

We assessed the seroprevalence of Entamoeba histolytica infection using indirect hemagglutination antibody (IHA) assay among 667 HIV-infected persons (group A), 1,311 asymptomatic HIV-uninfected persons seeking anonymous HIV testing (group B), 616 HIV-uninfected controls with gastrointestinal symptoms (diarrhea and/or liver abscess) seeking medical care (group C), and 2,500 healthy controls undergoing health check-up (group D). An IHA titer >or= 128 was detected in 7.1% of group A, 2.5% of group B, 1.8% of group C, and 0.1% of group D (P < 0.0001). The highest seroprevalence (11.2%) was noted among HIV-infected persons who were men having sex with men (MSM) 30-39 years of age. Compared with persons with gastrointestinal symptoms, the adjusted odds ratio for having high IHA titers among HIV-infected persons was 3.206 (95% confidence interval, 1.433, 7.176; P = 0.005). These findings show that HIV-infected persons, especially MSM 30-39 years of age, are at significantly higher risk of E. histolytica infection.     

Risk factors for in utero or intrapartum mother-to-child transmission of human immunodeficiency virus type 1 in Thailand

BACKGROUND: The identification of risk factors for in utero and intrapartum transmission of human immunodeficiency virus type 1 (HIV-1) is crucial to the design and understanding of preventive interventions.METHODS: The randomized Perinatal HIV Prevention Trial-1 enrolled 1437 pregnant women and their non-breast-fed infants, to compare the efficacy of various durations of zidovudine prophylaxis. Using univariate and multivariate logistic regression analyses, we studied the role that factors known or occurring at various times during gestation or delivery play in in utero and intrapartum transmission. RESULTS: Variables independently associated with in utero transmission were HIV-1 load >35,000 copies/mL (adjusted odds ratio [AOR], 4.2) and delayed initiation of maternal zidovudine prophylaxis until >31.4 weeks gestation (AOR, 3.0). Variables associated with intrapartum transmission were HIV-1 load >10,000 copies/mL (AOR, 3.8 for 10,000-35,000 copies/mL and 7.1 for >35,000 copies/mL), induction of labor (AOR, 2.6), and premature labor with tocolysis (AOR, 15.1).CONCLUSIONS: With the exception of very high HIV-1 load, risk factors for in utero transmission were different from those for intrapartum transmission. Optimal prophylactic interventions must address each of the major risk factors, with appropriate timing.     

Adaptive changes after human immunodeficiency virus type 1 transmission

Primary HIV-1 infection (PHI) is associated with a period of viremia, the resolution of which generally coincides with the development of both humoral and cellular immune responses. In this study replication-competent quasispecies were derived from virus isolated from an individual before and after seroconversion. Virus was also isolated from the presumed donor. Phenotypic and genotypic analysis of biological clones identified transmission of an R5/M-tropic phenotype. However, the ability of clones derived from the recipient to replicate in primary macrophages and PBMCs was restricted after transmission. This apparent selection process was supported by analysis of molecular clones derived from the isolated virus. Analysis of the ratio of synonymous and nonsynonymous substitutions predicted the existence of selective pressure soon after transmission, coincident with the development of HIV-1-specific antibodies. An Env trans-complementation assay demonstrated that the infectivity of a clone derived from the recipient after seroconversion was enhanced in the presence of a selected neutralizing antibody, indicating that the developing humoral immune response may have at least in part contributed to the selective pressure identified.     

Short-course antenatal zidovudine reduces both cervicovaginal human immunodeficiency virus type 1 RNA levels and risk of perinatal transmission. Bangkok Collaborative Perinatal HIV Transmission Study Group

Human immunodeficiency virus (HIV) levels in cervicovaginal lavage (CVL) and plasma samples were evaluated in relation to perinatal transmission in a randomized placebo-controlled trial of brief antenatal zidovudine treatment. Samples were collected at 38 weeks' gestation from 310 women and more frequently from a subset of 74 women. At 38 weeks, after a 2-week treatment period, CVL HIV-1 was quantifiable in 23% and 52% of samples in the zidovudine and placebo groups, respectively (P<.001). The perinatal transmission rate was 28.7% among women with quantifiable CVL HIV-1 and high plasma virus levels (>10,000 copies/mL) and 1% among women without quantifiable CVL HIV-1 and with low plasma virus levels (P<.001). A 1-log increase in plasma HIV-1 increased the transmission odds 1.8 and 6.1 times (95% confidence interval, 0.9-3.5 vs. 2.4-15.4) for women with and without quantifiable CVL HIV-1, respectively (P=.03). CVL HIV-1 is an independent risk factor for perinatal HIV-1 transmission.     

Hematological abnormalities in hemophilic patients with human immunodeficiency virus infection

Hematological abnormalities are common in patients with AIDS or AIDS-related complex. We studied cytological characteristics in peripheral blood and bone marrow samples of 33 hemophilic patients with HIV Infection and in six HIV negatives. The HIV-positive patients presented leukopenia (60.6%), thrombocytopenia (69.9%), and anemia (57.5%). Bone marrow showed abnormalities of maturation in one or more cell lines similar to those described in other HIV-infected groups of patients. These findings were more prominent in megakaryocytes and granulocytic series. Lymphocytosis, plasmocytosis, and increased hemophagocytosis were also common. These alterations do not appear in HIV-negative patients and seem related to a direct effect of HIV on bone marrow cells or to alterations in T-cell regulatory functions.     

Hepatitis C virus infection in individuals with or without human immunodeficiency virus type 1 infection

Summary Serum specimens from 111 human immunodeficiency virus type 1 (HIV-1) infected and 183 HIV-1 seronegative patients were analysed for antibodies to hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis A virus (HAV) by enzyme linked immunoassay (ELISA) and radioimmunoassay. Anti-HCV and anti-HBV antibodies were found in the vast majority (89 and 83%, respectively) of intravenous drug addicts (IVDA), independent of the type of drug abuse or whether the patients were HIV-1 infected or not. Anti-HAV antibodies were found in 60% of the IVDA. Anti-HCV antibodies were found in anti-HIV-1 positive homosexual men (14%) and anti-HIV-1 negative heterosexual persons (8%), but not in HIV-1 seronegative homosexual men. Also anti-HAV antibodies were found to a small extent in these groups. In contrast, anti-HBV antibodies were common in the homosexual men. The absorbance values of the positive reactions in the anti-HCV ELISA were lower for HIV-1 seropositive patients than those for HIV-1 seronegative subjects, particularly in the late stages of HIV-1 infection. These data suggest that HCV infection is transmitted as readily as HBV infection by intravenous drug abuse and that all three types of hepatitis virus infection are common in IVDA. Although transmission of HCV is primarily mediated by blood, sexual transmission may also occur. HIV-1 infection seems to be associated with unusually low levels of anti-HCV antibodies, especially in the late stages of HIV-1 infection.

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Hepatitis C Virus Infektionen bei HIV-1 Infizierten und nicht mit HIV-Inifizierten

Zusammenfassung Serumproben von 111 mit dem menschlichen Immunschwächevirus Typ 1 (HIV-1) Infizierten und von 183 HIV-1 seronegativen Patienten wurden auf Antikörper gegen das Hepatitis C Virus (HCV), Hepatitis B Virus (HBV) und Hepatitis A Virus (HAV) mittels enzymgebundenem Immunassay (ELISA) oder Radioimmunassay untersucht. Bei der überwiegenden Mehrzahl der i. v. Drogenabhängigen fanden sich Antikörper gegen HCV (89%) und HBV (83%). Dabei fand sich keine Korrelation zur Art der Droge oder HIV-Infektion. 60% der i. v. Drogenabhängigen hatten auch HAV-Antikörper. Unter den anti-HIV-1 positiven Männern wiesen 14% Antikörper gegen HCV auf. Anti-HIV negative heterosexuelle Personen waren zu 8% anti-HCV positiv. Unter den HIV-1 seronegativen homosexuellen Männern fanden sich in keinem Fall Antikörper gegen HCV. Ein kleiner Anteil der Personen dieser Gruppen wies auch Antikörper gegen HAV auf. Anti-HBV Antikörper fanden sich häufig bei homosexuellen Männern, wobei keine Abhängigkeit vom HIV-Serumstatus bestand. Bei HIV-1 seropositiven Patienten, und zwar besonders ausgeprägt im Spätstadium der HIV-Infektionen, waren die Absorptionswerte bei positivem anti-HCV ELISA niedriger als bei HIV-1 seronegativen Personen. Daraus läßt sich schließen, daß die HCV-Infektion wie die HBV-Infektion durch intravenösen Drogenmißbrauch übertragen wird und daß alle drei Typen der Virushepatitis bei i. v. Drogenabhängigen häufig sind. Obwohl die HCV-Übertragung hauptsächlich durch Blut erfolgt, ist eine sexuelle Übertragung ebenfalls möglich. Bei HIV-1 Infizierten sind die anti-HCV Antikörperspiegel ungewöhnlich niedrig, vor allem in den Spätstadien der Infektion.

     

Disease progression and survival with human immunodeficiency virus type 1 subtype E infection among female sex workers in Thailand

This study describes rates and correlates of disease progression and survival among 194 female sex workers in northern Thailand who were infected with human immunodeficiency virus type 1 (HIV-1; 96% with subtype E). The median rate of CD4 T lymphocyte decline (3.9 cells/microL/month), median time from infection to <200 CD4 T lymphocytes/microL (6.9 years), and time to 25% mortality (6.0 years) were similar to those found in studies performed in Western countries before highly active antiretroviral therapy was available to populations infected with HIV-1 subtype B. Mortality rates among women with >100,000 HIV-1 RNA copies/mL were 15.4 times higher (95% confidence interval, 5.2-45.2) than among women with <10,000 copies. Initial CD4 T lymphocyte counts and serum virus load were independently strong predictors of survival. These results can help in assessing the effects of the epidemic in Thailand and in determining the prognoses for individual patients.     

Maternal humoral factors associated with perinatal human immunodeficiency virus type-1 transmission in a cohort from Kigali, Rwanda, 1988-1994

OBJECTIVES: to study different parameters of humoral immunity responses in the serum of 39 human immunodeficiency virus type-1 infected pregnant women from Kigali, (Rwanda) in correlation with perinatal transmission. METHODS: this study was done between 1988 and 1994. Thirty nine HIV-1 infected women, 18 transmitting (T) and 21 non-transmitting (NT) mothers, have been chosen based on the quantity of sera available for analysis. Maternal data were collected at the time of delivery or during the preceding month. Quantification of viral load was performed by the signal amplification bDNA assay. Specific reactivity of antibody was tested against recombinant p24 protein and five different synthetic peptides from gp120 and gp41 based on HIV LAI-strain sequences. Neutralization assays were performed against laboratory (RII strain of the HIV-1 C subtype) and primary strains (two NSI and one SI of the HIV-1 A subtype). Antibody Dependent Cellular Cytotoxicity assay was performed with CEM.NK(R) cells against a laboratory HIV-1 strain. RESULTS: absence of correlation regarding maternal viral load, or viral subtype and vertical transmission was observed. By contrast, the CD4/CD8 ratio was significantly higher in non-transmitting mothers compared to transmitting mothers. Moreover, high anti-p24 antibody avidity was correlated with a lower risk of perinatal transmission. Furthermore, transmission risk appeared significantly higher with reactivity of serum samples to linear epitopes of gp41 (amino acids 566-582, 578-594), whereas risk appeared lower with reactivity to the immunodominant domain of gp41 (amino acids 597-609). No significant difference was observed in titres of antibody neutralizing primary isolates (two NSI (non syncitium inducer) and one SI (syncitium inducer) of the HIV-1 A subtype) and laboratory strain (RII strain, of the HIV-1 C subtype) between transmitting and non-transmitting mother's sera. In addition, titres of Antibody Dependent Cellular Cytotoxicity were similar in transmitting versus non-transmitting mothers. However, high Antibody Dependent Cellular Cytotoxicity titres were correlated with a good clinical status of children. CONCLUSIONS: three parameters such as high CD4/CD8 ratio, high anti-p24 antibody avidity and high reactivity against the immunodominant epitope of gp41 have been shown to be correlated with no perinatal transmission. High Antibody Dependent Cellular Cytotoxicity titres appeared to be linked to a good clinical status of children after birth. One parameter, reactivity against two linear epitopes of gp41, appeared to be correlated with vertical transmission.     

Human immunodeficiency virus (HIV) type 1 antibodies in perinatal HIV-1 infection: association with human HIV-1 transmission, infection, and disease progression. For the Women and Infants Transmission Study

Anti -human immunodeficiency virus (HIV) type 1 antibodies in 242 pregnant women and 238 infants were measured at birth and at 1, 2, 4, and 6 months after birth, to estimate their association with perinatal transmission and infant disease progression. Maternal anti-p24 (P=.01) and anti-gp120 (P=.04) antibodies were inversely associated with vertical transmission rates, independent of maternal percentage of CD4 cells, hard drug use, duration of ruptured membranes, serum albumin levels, serum vitamin A levels, and quantitative HIV-1 peripheral mononuclear blood cell culture, but not with maternal plasma immune complex dissociated p24 or HIV-1 RNA copy number, both of which were highly correlated with antibodies. From ages 1-2 months, anti-gp120, -gp41, -p31, and -p66 decayed to a greater extent in infected than in uninfected infants. Infected infants produced anti-p24 antibody by age 2 months, anti-p17 by 4 months, and anti-p41 and anti-gp120 by 6 months. As early as birth, infants with rapid disease progression had lower levels of anti-p24 than did infants whose disease did not rapidly progress, but not independently of HIV-1 RNA levels.     

Human immunodeficiency virus load in breast milk, mastitis, and mother-to-child transmission of human immunodeficiency virus type 1.

Human immunodeficiency virus (HIV) type 1 load in breast milk and mastitis were examined as risk factors for vertical transmission of HIV-1. Six weeks after delivery, HIV-1 load and sodium (an indicator of mastitis) were measured in breast milk from 334 HIV-1-infected women in Malawi. Median breast milk HIV-1 load was 700 copies/mL among women with HIV-1-infected infants versus undetectable (<200 copies/mL) among those with uninfected infants, respectively (P<. 0001). Elevated breast milk sodium levels consistent with mastitis occurred in 16.4% of HIV-1-infected women and were associated with increased vertical transmission of HIV-1 (P<.0001). Median breast milk HIV-1 load was 920 copies/mL among women with versus undetectable among those without elevated breast milk sodium levels, respectively (P<.0001). Mastitis and breast milk HIV-1 load may increase the risk of vertical transmission of HIV-1 through breast-feeding.