A prospective study of infants born to women seropositive for human immunodeficiency virus type 1. HIV Infection in Newborns French Collaborative Study Group

Assessment of the risks of transmission of infection with human immunodeficiency virus type 1 (HIV-1) from mother to newborn is difficult, partly because of the persistence for up to a year of maternal antibodies transmitted passively to the infant. To determine the frequency of perinatal transmission of HIV infection, we studied from birth 308 infants born to seropositive women, 62 percent of whom were intravenous drug abusers. Of 117 infants evaluated 18 months after birth, 32 (27 percent) were seropositive for HIV or had died of the acquired immunodeficiency syndrome (AIDS) (n = 6); of the 32, only 2 remained asymptomatic. Another 76 infants (65 percent) were seronegative and free of symptoms, whereas 9 (8 percent) were seronegative but had symptoms suggestive of HIV-1 infection. The infants infected with HIV-1 did not differ from the others at birth with respect to weight, height, head circumference, or rate of malformations, but as compared with newborns who were seronegative at 18 months, their serum IgM levels were higher (78 +/- 81 mg per deciliter vs. 38 +/- 39 mg per deciliter; P less than 0.03) and their CD4 lymphocyte counts were lower (2054 +/- 1221 per cubic millimeter vs. 2901 +/- 1195 per cubic millimeter; P less than 0.006). Neither maternal risk factors nor the route of delivery was a predictor of seropositivity at 18 months; however, 5 of the 6 infants who were breast-fed became seropositive, as compared with 25 of 99 who were not (P less than 0.01). We conclude that approximately one third of the infants born to seropositive mothers will have evidence of HIV-1 infection or of AIDS by the age of 18 months, and that about one fifth of this group will have died.     

Frequency of CCR5-Delta32 deletion in human immunodeficiency virus type 1 (HIV-1) in healthy blood donors, HIV-1-exposed seronegative and HIV-1-seropositive individuals of southern Brazilian population

The frequency of CCR5-Delta32 allele in human immunodeficiency virus type 1 (HIV-1) infection in the southern Brazilian population was determined in a cross-sectional study carried out from October 2001 to June 2004. Genomic DNA was extracted from peripheral blood cells of 134 healthy blood donors, 145 HIV-1-exposed seronegative individuals, 152 HIV-1-seropositive asymptomatic individuals, and 478 HIV-1-seropositive individuals with AIDS. A fragment with 225 base-pairs of the CCR5 gene was amplified by polymerase chain reaction. The CCR5-Delta32 homozygous deletion was observed in 2 (1.5%) blood donors and in 1 (0.7%) individual HIV-1-exposed seronegative, and was absent among all the HIV-1-seropositive individuals (Fisher's exact test, p=0.0242). The frequency of the homozygous CCR5-Delta32 deletion in the HIV-1-exposed did not differ when compared with that observed in the HIV-1 seronegative blood donors (Fisher's exact test, p=0.6093; OR: 2.18, 95% CI: 0.11-129.6). The wild-type genotype CCR5/CCR5 frequency was higher among the HIV-1-seropositive with AIDS compared to HIV-1 seropositive asymptomatic individuals (Chi-square test, p=0.0263; OR: 2.02, 95% CI: 1.03-3.97). The absence of the homozygous deletion of CCR5-Delta32 among HIV-1-seropositive individuals underscored that this genotype is an important genetic factor associated with the decreased susceptibility to HIV-1 infection. The higher frequency of heterozygosity for the CCR5-Delta32 and the CCR5-Delta32 allele in HIV-1 seropositive asymptomatic compared to HIV-seropositive with AIDS individuals also underscored that this deletion could be associated with the delay of the HIV-1 disease progression in this population. However, the low frequency of CCR5-Delta32 homozygosity observed among HIV-1-exposed seronegative individuals shows that the allele could not explain, by itself, the natural resistance to HIV-1 infection and different mechanisms of protection against HIV-1 infection that must be involved in this population.     

Effect of prenatal zidovudine on disease progression in perinatally HIV-1-infected infants

OBJECTIVE: To determine the influence of prenatal zidovudine (ZDV) prophylaxis on the course of HIV- 1 infection in children by comparing the clinical outcome of infants born to HIV- 1-seropositive mothers who did versus those who did not receive ZDV during pregnancy. METHODS: Medical records of HIV-1-seropositive mothers and their infants were reviewed retrospectively. Participants were divided according to maternal ZDV use: no ZDV (n = 152); ZDV (n = 139). The main outcome measure was rapid disease progression (RPD) in the infant, defined as occurrence of a category C disease or AIDS-related death before 18 months of age. RESULTS: HIV vertical transmission rates were significantly different (no ZDV versus ZDV: 22.3% versus 12.2%; p = .034). Among infected infants, the RPD rate was 29.4% in the no ZDV group compared with 70.6% in the ZDV group (p = .012), and prematurity was significantly associated with a higher risk of RPD (p = .027). CONCLUSIONS: The rate of RPD was significantly higher among perinatally infected infants born to HIV-infected mothers treated with ZDV than among infected infants born to untreated mothers. The decreased proportion of infected infants with nonrapid disease progression in the former group might be related to the ability of ZDV to block intrapartum transmission preferentially and also to nonrapid disease progression resulting from intrapartum transmission.     

Cytotoxic T lymphocyte responses in the peripheral blood of children born to human immunodeficiency virus-1-infected mothers.

Cytotoxic T lymphocytes (CTL) are present at high activities in adult patients infected with the human immunodeficiency virus (HIV). In this report, CTL effectors were identified in peripheral blood mononuclear cells (PBMC) of children born to HIV-1-infected mothers. These CTL killed HLA-matched HIV-1-infected H9 target cells or doubly transfected P815-A2-env, gag or nef mouse tumor cells, which expressed the viral antigens in association with HLA-A1/A3 or HLA-A2, respectively. HIV-1-specific CTL were detected early after birth (less than 2 months) and remained present during the asymptomatic phase of the infection. As in HIV-1-infected adults, HIV-specific CTL declined with disease progression. Surprisingly, HIV-1-specific CTL were detected in the PBMC of three children who subsequently became seronegative.     

Lack of association between maternal antibody and protection of African infants from malaria infection

Maternally derived antibodies are believed to protect infants against infection, but there is little direct evidence for a protective role of passively acquired antibodies against malaria. A longitudinal study of malaria infection in 143 infants was conducted in a region of southern Ghana where Plasmodium falciparum is endemic. Infants born in the high-transmission season were less likely to become infected in the first 20 weeks of life than children born in the low-transmission season. Plasma, obtained at birth, was tested for immunoglobulin G (IgG) and IgG subclasses to P. falciparum schizonts and recombinant circumsporozoite antigen, MSP-1(19), MSP-2, AMA-1, and Pf155 (also called ring-infected erythrocyte surface antigen). Antibody levels at birth were not associated with resistance to malaria infection. On the contrary, antibodies at birth were positively associated with infection, indicating that high levels of maternally derived antibodies represent a marker for intensity of exposure to malaria infection in infants. However, all five children who experienced high-density infections (>100 parasites/microl of blood) were seronegative for MSP-1(19) at the time of infection.     

Reliable confirmation of antibodies to human immunodeficiency virus type 1 (HIV-1) with an enzyme-linked immunoassay using recombinant antigens derived from the HIV-1 gag, pol, and env genes.

An enzyme-linked immunoassay (ELISA) using six recombinant proteins corresponding to large segments of the human immunodeficiency virus type 1 (HIV-1) gag, pol, and env gene products (HIVAGEN; SmithKline Bio-Science Laboratories, Van Nuys, Calif.) was developed to confirm the presence of antibodies to HIV-1 in sera reactive in the whole-cell-derived virion screening ELISAs. Serum samples for testing were obtained from healthy seronegative blood donors and from the different categories of HIV-infected individuals (asymptomatic, acquired immunodeficiency syndrome [AIDS]-related complex, and AIDS). A positive reaction was defined as reactivity against an env and at least one other (either gag or pol) HIV-1 gene product; negative was defined as no reaction with any antigen; and indeterminate was defined as reactivity with gag or pol (or both) or with env alone. None of the 1,180 serum samples from healthy seronegative blood donors gave a positive result, and only 49 of these samples (4%) gave indeterminate results. The recombinant HIV-1 antigen ELISA panel identified seropositive individuals with a high degree of accuracy, as a positive reaction was seen with 99.3% of asymptomatic healthy seropositive individuals, 98.1% of patients with AIDS-related complex, and 90.4% of patients with AIDS. None of the 725 HIV-1-seropositive subjects had a negative test result. Reactivity with the Kp41 antigen, corresponding to an amino-terminal portion of the gp41 envelope glycoprotein, by itself demonstrated 100% sensitivity and specificity in distinguishing seronegative from seropositive sera. A subset of seronegative and seropositive samples were tested both with the recombinant HIV-1 antigen ELISA panel and by Western blot (Du Pont Co.). The recombinant HIV-1 antigen ELISA panel accurately identified more seropositive and seronegative samples and had fewer indeterminate results than did Western blot (interpreted by Du Pont criteria).     

Perinatal transmission of the human immunodeficiency virus type 1 to infants of seropositive women in Zaire

To examine perinatal transmission of the human immunodeficiency virus type 1 (HIV-1) in Zaire, we screened 8108 women who gave birth at one of two Kinshasa hospitals that serve populations of markedly different socioeconomic status. For up to one year, we followed the 475 infants of the 466 seropositive women (5.8 percent of those screened) and the 616 infants of 606 seronegative women matched for age, parity, and hospital. On the basis of clinical criteria, 85 of the seropositive women (18 percent) had the acquired immunodeficiency syndrome (AIDS). The infants of seropositive mothers, as compared with those of seronegative mothers, were more frequently premature, had lower birth weights, and had a higher death rate in the first 28 days (6.2 vs. 1.2 percent; P less than 0.0001). The patterns were similar at the two hospitals. Twenty-one percent of the cultures for HIV-1 of 92 randomly selected cord-blood samples from infants of seropositive women were positive. T4-cell counts were performed in 37 seropositive women, and cord blood from their infants was cultured. The cultures were positive in the infants of 6 of the 18 women with antepartum T4 counts of 400 or fewer cells per cubic millimeter, as compared with none of the infants of the 19 women with more than 400 T4 cells per cubic millimeter (P = 0.02). One year later, 21 percent of the infants of the seropositive mothers had died as compared with 3.8 percent of the control infants (P less than 0.001), and 7.9 percent of their surviving infants had AIDS. We conclude that the mortality rates among children of seropositive mothers are high regardless of socioeconomic status, and that perinatal transmission of HIV-1 has a major adverse effect on infant survival in Kinshasa.     

Postnatal transmission of human immunodeficiency virus type 1 from mother to infant. A prospective cohort study in Kigali, Rwanda.

BACKGROUND. Although transmission of human immunodeficiency virus type 1 (HIV-1) from mother to infant has been well documented during pregnancy and delivery, little is known about the possible transmission of HIV-1 during the postnatal period. METHODS. We conducted a prospective cohort study in Kigali, Rwanda, of 212 mother-infant pairs who were seronegative for HIV-1 at delivery. All the infants were breast-fed. The subjects were followed at three-month intervals, with Western blot assays for antibodies to HIV-1 and testing of mononuclear cells by a double polymerase chain reaction (PCR) using three sets of primers. To evaluate potential risk factors, each mother who seroconverted was matched with three seronegative control women. RESULTS. After a mean follow-up of 16.6 months, 16 of the 212 mothers became seropositive for HIV-1. Of their 16 infants, 9 became seropositive. One infant was excluded from the analysis because of a positive test by PCR on the blood sample obtained at birth. Postnatal seroconversion to HIV-1 occurred in four of the five infants born to the mothers who seroconverted during the first 3 months post partum, and in four infants of the 10 mothers who seroconverted between month 4 and month 21. In all cases, the infant seroconverted during the same three-month period as the mother. The main risk factor for maternal seroconversion was being single. CONCLUSIONS. HIV-1 infection can be transmitted from mothers to infants during the postnatal period. Colostrum and breast milk may be efficient routes for the transmission of HIV-1 from recently infected mothers to their infants.     

Broad Spectrum of Time of Detection, Primary Symptoms and Disease Progression in Infants with HIV-1 Infection

 The relationship between time of HIV-1 detection, appearance of symptoms and disease progression was studied in all 24 HIV-1-infected infants from a cohort of 117 children who were born to HIV-1-infected mothers and monitored from birth. HIV isolation from plasma and mononuclear cells, HIV-1 DNA PCR (polymerase chain reaction) and, retrospectively, a quantitative assay for HIV-1 RNA were used for virus detection. Two infants possibly exhibited a symptomatic primary HIV infection. More children with than without symptoms during the first year of life progressed to immunological class 3 (P=0.013) and to AIDS or death (P=0.003) during follow-up. HIV-1 was detected within 4 days of age in 4 of 16 infants: 3 of them became symptomatic within 1 year, as did 6 of the remaining 12 infants (not statistically significant). All four infants in whom virus was detected within 4 days of age progressed to severe immunosuppression, compared to 6 of 14 in whom the virus detection test was initially negative prior to the first positive result (n.s.). Two children with previous repeatedly negative HIV detection tests were diagnosed with HIV-1 infection at 8 and 9 months, respectively. Repeated blood sampling is needed for the diagnosis of HIV-1 infection in perinatally exposed infants, and virus detection tests for exclusion of HIV-1 infection must be used with caution.     

Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor.

BACKGROUND AND METHODS. To define the risk factors associated with neonatal acquisition of herpes simplex virus (HSV) infection, we prospectively obtained HSV cultures from the cervix and external genitalia of 15,923 pregnant women in early labor who were without symptoms or signs of genital HSV infection. Follow-up of the women with positive cultures for HSV and their HSV-exposed infants included serologic tests and serial cultures for HSV. RESULTS. HSV was isolated from 56 of the women (0.35 percent), 18 of whom (35 percent) had serologic evidence of a recently acquired, subclinical first episode of genital HSV infection, and 34 of whom (65 percent) had reactivation of HSV. Neonatal HSV developed in 6 of 18 infants (33 percent) born to the women with a first episode of genital HSV, and in 1 of 34 infants (3 percent) born to the women with reactivation of HSV (P less than 0.01); neonatal HSV also occurred in three of the infants born to the 15,867 women with negative cultures. Neonatal HSV-2 occurred in 1 of 4 infants born to mothers seronegative at delivery for both HSV-1 and HSV-2, in 4 of 12 infants exposed to HSV-2 whose mothers had only HSV-1 antibodies at delivery, and in none of the infants born to 31 women who were HSV-2-seropositive. An increased risk of neonatal HSV was associated with exposure to viral shedding from the cervix and the use of fetal-scalp electrodes. CONCLUSIONS: Of the asymptomatic women who shed HSV in early labor, about a third have recently acquired genital HSV, and their infants are 10 times more likely to have neonatal HSV than those of women with asymptomatic reactivation of HSV. The presence of maternal antibodies specific to HSV-2 but not HSV-1 appears to reduce the neonatal transmission of HSV-2. Further studies are necessary to determine whether screening and prophylactic treatment are warranted for infants of HSV-2-seronegative mothers who shed HSV-1 or HSV-2 in early labor.     

Direct detection of proviral gag segment of human immunodeficiency virus in peripheral blood lymphocytes by colorimetric PCR assay as a clinical laboratory tool applied to different at-risk populations.

We used a colorimetric polymerase chain reaction (PCR)-based assay in kit form to detect directly human immunodeficiency virus type 1 (HIV-1) proviral gag sequences in peripheral blood cells from 68 healthy blood donors, 51 subjects at risk for HIV infection, 122 patients with HIV-1 infection, 11 patients with indeterminate Western blot (immunoblot) results, 4 blood donors HIV-1 positive by enzyme immunoassay, and 13 children born to HIV-1-seropositive mothers. The results obtained in the blood donors and HIV-1-infected patients demonstrated the high degree of diagnostic specificity and sensitivity of the PCR method. HIV-1 infection was excluded in 10 of the 11 patients with indeterminate Western blot results and in all four enzyme immunoassay-positive blood donors. A diagnosis of HIV infection was ruled out by negative PCR results in 5 of 13 children from seropositive mothers, which excluded vertical transmission of the infection in these cases; these children were younger than 3 months and had positive serological results. Two at-risk patients with negative serological results had positive PCR results. All results were confirmed by conventional PCR. In conclusion, colorimetric PCR, which is commercially available in kit form, is an easy and reliable technique that can be used to detect proviral HIV-1 genomes in blood cells, and despite the limitations owing to HIV genome variability, it is useful in the clinical setting for the diagnosis of HIV infection in selected categories of patients.     

Immunoblotting analysis of IgA and IgM antibody to human immunodeficiency virus type 1 (HIV-1) polypeptides in seropositive infants

Seventy infants born to human immunodeficiency virus type 1 (HIV-1) seropositive mothers were studied for specific antibody (IgA, IgM and IgG) production and the presence of active infection (detectable level of virus in peripheral blood lymphocytes). Among these children, followed for up to 15–40 months after birth, 11 presented unequivocal signs of HIV-1 infection (persistent p24 antigenemia and/or positive virus isolation). Analysis of sera by immunoblotting showed that IgA antibody to HIV-1 p24 core protein, alone or associated with envelope glycoproteins (gp120, gp41), was present in the majority of infected babies (7 of 11), while IgM was found in a lower percentage of cases (4 of 11). No IgA and or IgM antibody to HIV-1 was ever found in babies, born to seropositive mothers, who seroreverted after birth or in the control group enrolled in this study. Our results indicate that immunoblotting analysis of IgA antibody to HIV-1 polypeptides may represent a useful complementary prognostic marker in children born to HIV-1 seropositive mothers.     

HIV-1, HIV-2, and HTLV-I infection in high-risk groups in Brazil

We conducted a serologic survey for antibodies to human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and human T-cell lymphotropic virus Type I (HTLV-I) in 704 Brazilians with the acquired immunodeficiency syndrome (AIDS) or at risk for it. The study population included 70 homosexual men (11 of whom were prostitutes), 58 bisexual men (19 of whom were prostitutes), 101 female prostitutes from three socioeconomic groups, 13 wives of men with hemophilia who were seropositive for HIV-1 antibodies, and 47 blood donors with positive Venereal Disease Research Laboratory tests for syphilis, all from Rio de Janeiro; 86 female prostitutes from two rural towns in Minas Gerais; 133 patients with AIDS from S?o Paulo; and 196 men with bleeding disorders who were seropositive for HIV-1 antibodies on enzyme-linked immunosorbent assay, from S?o Paulo and Rio de Janeiro. The prevalence of HIV-1 infection was highest in the homosexual male prostitutes (45 percent), the wives of patients with hemophilia (38 percent), the bisexual men (28 percent), the homosexual men who were not prostitutes (19 percent), and the female prostitutes from the lower class (9 percent). Combined HIV-1 and HIV-2 infection was found in 3 percent of the patients with AIDS and in 1 percent of the homosexual men. The prevalence of HTLV-I infection ranged from 1 percent in rural female prostitutes to 13 percent in HIV-1-positive men with bleeding disorders in Rio de Janeiro. Combined HIV-1 and HTLV-I infection occurred in 1 to 11 percent of some male subgroups. We conclude that in Brazil HIV-1 infection is already well established among homosexuals, bisexuals, and lower-class female prostitutes, with bisexual men probably acting as a bridge between the heterosexual and homosexual communities, that HTLV-I infection is prevalent in groups at risk for AIDS, and that HIV-2 infection has already been introduced into the country.     

Levels of circulating fibronectin receptor in adult and pediatric patients with human immunodeficiency virus type 1 infection.

We found a significant increase in fibronectin receptor (FNR) levels in the sera of adult human immunodeficiency virus type 1 (HIV-1)-infected patients, especially in those with AIDS (1,026.9 +/- 583.9 ng/ml; P < 0.0001). In contrast, AIDS patients with neurologic disorders and HIV-1-seropositive patients showed normal levels of FNR in serum. In addition, HIV-1-infected children showed increased levels of FNR in serum (824.4 +/- 333.5 ng/ml; P = 0.03). We suggest that an increase of FNR levels in AIDS patients is related to enhanced expression of FNR on HIV-1-infected cells.     

Anti-leukocyte antibodies as a consequence of HIV infection in HIV+ individuals.

Antibodies (Ab) that induce antibody-dependent cell-mediated cytotoxicity (ADCC) against non-T lymphocytes, anti-HLA class II specific Ab and anti-PMN were tested in hemophilic (He) patients who were alloimmunized because they had received replacement treatment with blood derivates and become infected with HIV, as well as in those who remained seronegative. In addition, the serum reactivity of spouses of HIV+ individuals and their children was studied to determine the effect of HIV infection in the absence of concomitant alloimmunization. The results of this study indicate that ADCC Ab were already present in HIV- He, suggesting the influence of alloimmunization. Their titer increased after appearance of HIV disease. While low reactivity against class II antigens was observed in HIV- He, activity augmented sharply after HIV infection and increased further with disease progression. Anti-PMN reactivity followed a similar pattern. Anti-class II, ADCC Ab and anti-PMN were also detected in the asymptomatic HIV+ spouses of HIV+ patients in titers that were similar to those of asymptomatic HIV+ He. In children born to HIV+ mothers in whom HIV infection was confirmed, anti-class II, ADCC Ab and anti-PMN reactivity were also observed, and activity increased after the onset of disease. These results suggest that induction of anti-leukocyte Ab occurs in the absence of massive allostimulation after HIV infection. HIV infection may enhance preexisting class II and anti-leukocyte response in allostimulated individuals.     

Use of the polymerase chain reaction for early detection of the proviral sequences of human immunodeficiency virus in infants born to seropositive mothers. New York City Collaborative Study of Maternal HIV Transmission and Montefiore Medical Center HIV Perinatal Transmission Study Group

The early diagnosis of infection with human immunodeficiency virus (HIV) in infants born to infected mothers is essential for early treatment, but current tests cannot detect HIV infection in newborns because of the presence of maternal antibodies. We used the polymerase chain reaction, a new technique that amplifies proviral sequences of HIV within DNA, to detect HIV infection in peripheral-blood mononuclear cells obtained from infants of seropositive women during the neonatal (age less than 28 days) and postneonatal periods. In blood obtained during the neonatal period, the polymerase chain reaction was positive in five of seven infants in whom the acquired immunodeficiency syndrome (AIDS) later developed (a mean of 9.8 months after the test). The test was also positive in one of eight newborns who later had nonspecific signs and symptoms suggestive of HIV infection (mean follow-up, 12 months). No proviral sequences were detected in neonatal samples from nine infants who remained well (mean follow-up, 16 months). HIV proviral sequences were detected in samples obtained during the postneonatal period (median age, five months) in all of 6 infants tested who later had AIDS and in 4 of 14 infants with nonspecific findings suggestive of HIV infection. No proviral sequences were detected in 25 infants who remained well (mean follow-up, 17 months) after being born to HIV-seropositive mothers, or in 15 infants born to HIV-seronegative mothers. We conclude that the polymerase chain reaction will be a useful technique to diagnose HIV infection in newborns and to predict the subsequent development of AIDS. However, larger studies will be required to determine the sensitivity and specificity of the test.     

Rapid screening for early detection of mother-to-child transmission of human immunodeficiency virus type 1.

The testing of dried blood spots (DBSs) for the presence of human immunodeficiency type 1 (HIV-1) proviral DNA by PCR was first described in 1991. The technology has proven to be particularly valuable for resolving the infection status in HIV-1-indeterminate infants born to HIV-1-seropositive mothers. To broaden the applicability of DBS PCR, we adapted it to a standardized, commercially available microwell plate amplification and detection kit, Amplicor HIV-1, produced by Roche Diagnostic Systems. The microwell assay is rapid and easy to perform and uses equipment that is readily available in routine diagnostic laboratories. The high level of performance of the assay was demonstrated in 1,168 duplicate tests performed on 584 DBSs from 178 uninfected and 100 HIV-1-infected individuals, including 56 children with perinatally acquired HIV-1. Of 12 infants who were followed prospectively from birth, 3 (25%) were infected in utero (PCR positive at birth) and 9 (75%) were infected intrapartum (PCR negative, culture negative at birth). Overall, HIV-1 DNA was identified in 3 of 11 (27.3%) DBSs collected from infected infants during the first 4 days of life, 8 of 9 (88.9%) DBSs collected between 10 and 15 days postpartum, and 166 of 167 (99.4%) DBSs collected after 15 days of age. All 320 DBSs from uninfected children were PCR DNA negative. These findings indicate that use of the Roche microwell DBS PCR assay provides a powerful new approach for large-scale perinatal screening programs and population-based studies of vertical transmission.     

Neutralizing antibodies as a prognostic indicator in the progression of acquired immune deficiency syndrome (AIDS)-related disorders: A double-blind study

A double-blind longitudinal study for the presence of human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies (NAb) in the sera of 36 patients with acquired immune deficiency syndrome (AIDS), 149 prodromal homosexual subjects, and 33 heterosexual subjects has been carried out. All AIDS patients and 68% of prodromal homosexual subjects (101/149) were found to be HIV-1 antibody positive by Western blot assay. All heterosexual subjects were HIV-1 antibody negative. Neutralizing antibody(s) was determined by testing the protective activity of sera against HIV-1 infection of human T-cell line H9. Study subjects were divided into NAb(+) (antibody titer, >1:40) and NAb(–) (antibody titer, <1:40) groups. During the 24-month observation period 2 of 80 (3%) HIV-1(+) NAb(+) individuals progressed to AIDS and died, as compared to 5 of 21 (24%) of HIV-1(+) NAb(–) subjects who progressed to AIDS. Similarly, among the NAb(+) AIDS patients 8 of 23 (35%) died, while 10 of 13 (77%) of the NAb(–) patients died during the course of the study. In addition, the absence or reduction of HIV-1 p17 and p24 antibodies directed against HIV-1 antigens as well as the low titer or absence of NAb appears to be closely related to the clinical progression of the disease. These studies suggest that a decrease in the virus neutralization capacity of the sera and a decrease or complete loss of HIV-1 p17 and p24 antibodies may be useful as prognostic indicators for the progression of disease in HIV-1-seropositive patients.     

Detection of human immunodeficiency virus type 1 (HIV-1) in heel prick blood on filter paper from children born to HIV-1-seropositive mothers.

The human immunodeficiency virus type 1 (HIV-1) DNA PCR results of 94 dried blood spot (DBS) samples on filter paper and corresponding venous blood in EDTA obtained from infants born to HIV-1-seropositive mothers were compared. In addition, the results of HIV-1 DNA PCR on DBS and the HIV-1 RNA PCR from plasma of 70 paired samples were compared. A 100% specificity and a 95% sensitivity for HIV-1 DNA PCR on DBS compared with results for venous blood were observed for the 94 paired samples. The results of the DBS HIV-1 DNA PCR and HIV-1 RNA PCR of 70 corresponding plasma samples correlated perfectly (100%). The DBS HIV-1 DNA PCR method proved reliable for HIV-1 detection.