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PubMed1997

Long-term resistance to HIV infection in vertical HIV infection: cytokine production, HIV isolation, and HIV phenotype define long-term resistant hosts.

We analyzed immunologic (CD4 and CD8 slopes; interferon-gamma, interleukin-2, interleukin-10, and chemokines production; concentration of IgE; beta 2-microglobulin) and virologic (p24; HIV isolability and phenotype; plasma viremia) parameters in HIV vertically infected children > or = 8 years of age without disease progression or mild symptoms and an absolute CD4+ count > or = 500/microliter with CD4+ percentage > or = 25%. The results were compared to those of two control groups: (1) slow progressors, children > or = 8 years of age with moderate symptomatology and/or moderate CD4 depletion, and (2) progressors, children > or = 8 years of age with severe clinical disease and/or severe CD4 depletion. Pediatric long-term resistant hosts were characterized by higher production of interleukin-2 and interferon-gamma and lower production of interleukin-10, normal concentration of IgE, HIV isolates with a non-syncytium-inducing phenotype, and lower plasma viremia. This condition was not associated with the concentration of beta 2-microglobulin, p24, and chemokines, or with HIV isolability. The IL-10/IL-2 ratio best correlated with both CD4 counts and disease progression. Thus, vertically infected children showing resistance to disease progression are immunologically and virologically distinct from those in whom progressive HIV infection is observed.

Adolescent↗
PubMed1997

Presence of human immunodeficiency virus (HIV) type 1 subtype A infection in a New York community with high HIV prevalence: a sentinel site for monitoring HIV genetic diversity in North America. Centers for Disease Control and Prevention-Bronx Lebanon HIV Serosurvey Team.

To determine whether US residents are infected with subtypes of human immunodeficiency virus (HIV) type 1 other than subtype B (Western), the predominant North American subtype with a unique GPGR genetic sequence in the V3 loop, viruses from 22 HIV-infected adults were serotyped and subtyped. Twenty patients had subtype B (Western), of whom 15 had serotype B (Western), 3 had serotype A/C, 1 had serotype B (Thai), and 1 had a nontypeable serotype. Two had subtype A, both serotype A/C. Both subtype A-infected patients, only 1 of whom had been outside the United States, reported sex with persons traveling abroad, suggesting possible acquisition in the United States. Because US residents are infected with non-subtype B (Western) strains, US surveillance for HIV-1 diversity is needed to elucidate subtype-specific transmission patterns and pathogenesis and to guide evaluation and development of HIV diagnostic tests and vaccines.

Adolescent↗
PubMed2000

Cardiac dysfunction and mortality in HIV-infected children: The Prospective P2C2 HIV Multicenter Study. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study Group.

BACKGROUND: Left ventricular (LV) dysfunction is common in children infected with the human immunodeficiency virus (HIV), but its clinical importance is unclear. Our objective was to determine whether abnormalities of LV structure and function independently predict all-cause mortality in HIV-infected children. METHODS AND RESULTS: Baseline echocardiograms were obtained on 193 children with vertically transmitted HIV infection (median age, 2.1 years). Children were followed up for a median of 5 years. Cox regression was used to identify measures of LV structure and function predictive of mortality after adjustment for other important demographic and baseline clinical risk factors. The time course of cardiac variables before mortality was also examined. The 5-year cumulative survival was 64%. Mortality was higher in children who, at baseline, had depressed LV fractional shortening (FS) or contractility; increased LV dimension, thickness, mass, or wall stress; or increased heart rate or blood pressure (P0.02 for each). Decreased LV FS (P<0.001) and increased wall thickness (P=0.004) were also predictive of increased mortality after adjustment for CD4 count (P<0.001), clinical center (P<0.001), and encephalopathy (P<0.001). FS showed abnormalities for up to 3 years before death, whereas wall thickness identified a population at risk only 18 to 24 months before death. CONCLUSIONS: Depressed LV FS and increased wall thickness are risk factors for mortality in HIV-infected children independent of depressed CD4 cell count and neurological disease. FS may be useful as a long-term predictor and wall thickness as a short-term predictor of mortality.

Cardiovascular Diseases↗
PubMed1998

Field evaluation of a combination of monospecific enzyme-linked immunosorbent assays for type-specific diagnosis of human immunodeficiency virus type 1 (HIV-1) and HIV-2 infections in HIV-seropositive persons in Abidjan, Ivory Coast.

Serologic distinction between human immunodeficiency virus type 1 (HIV-1) and HIV-2 infection is made difficult because of the cross-reactivity and high cost of existing differentiation assays. An evaluation of a strategy based on a combination of monospecific enzyme-linked immunosorbent assays (ELISAs) (CME), was carried out in Abidjan, Ivory Coast, where both HIV-1 and HIV-2 are present, to determine its accuracy and cost-effectiveness. A total of 1,608 (428 HIV-1-positive, 361 HIV-2-positive, 371 dually HIV-1 and HIV-2 [HIV-D] reactive, and 448 HIV-negative) sera that had been serotyped by a line immunoassay (Peptilav) were tested retrospectively by an HIV-1-monospecific (Wellcozyme HIV Recombinant ELISA) and an HIV-2-monospecific (ICE*-HIV-2) assay. The CME strategy gave concordant results for all of the 428 sera scored as HIV-1 by Peptilav. Of the 361 sera scored as HIV-2 by Peptilav, 316 (87.5%) were scored as HIV-2 by CME; the remaining 45 sera were positive by both monospecific ELISAs (mean optical density ratios, 1.36 for Wellcozyme and 11.30 for ICE*-HIV-2) and were classified as HIV-D by CME. Of the 371 sera classified as HIV-D by Peptilav, 344 (92.7%), 21, and 6 were scored as HIV-D, HIV-1, and HIV-2, respectively, by CME. Additional testing of the discrepant samples by two HIV differentiation assays (RIBA and INNO-LIA) gave results that agreed with those by CME for most of the sera. In addition, 267 other sera were tested prospectively by both CME and Peptilav. In the prospective evaluation, CME results agreed with those by Peptilav for all 106 HIV-1 sera and 40 of the 41 HIV-2 sera. However, of the 120 sera scored as HIV-D by Peptilav, 69 (57.5%), 47 (39.2%), and 4 (3.3%) were scored as HIV-D, HIV-1 only, and HIV-2 only, respectively, by CME. All 47 samples scored as HIV-1 by CME and two of four HIV-2 sera gave concordant results by RIBA, whereas 29 of 47 sera scored as HIV-1 by CME and all four HIV-2 sera gave concordant results by INNO-LIA. The reagent cost for the CME strategy was 59% lower than the cost of the Peptilav strategy. These results suggest that a combination of highly sensitive and specific commercially available monospecific ELISAs is a reliable and cost-effective strategy for type-specific serodiagnosis of HIV-1 and HIV-2 infections in HIV-seropositive persons and therefore represents a recommended strategy in areas where both HIV-1 and HIV-2 are endemic.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Use of human immunodeficiency virus (HIV) type 1 and 2 recombinant strip immunoblot assay to resolve enzyme immunoassay anti-HIV-2-repeatably reactive samples after anti-HIV-1/2 combination enzyme immunoassay screening.

BACKGROUND: With the implementation of combination human immunodeficiency virus types 1 and 2 (HIV-1/2) antibody enzyme immunoassay (EIA) in donor screening in 1992, the supplemental testing algorithm changed to require the use of a Food and Drug Administration (FDA)-licensed HIV-1 Western blot (WB) or immunofluorescence assay, as well as an FDA-licensed HIV-2 EIA. When HIV-2 EIA-reactive specimens are identified, further testing to confirm HIV-2 infection is recommended. Currently, a licensed HIV-2 supplemental assay is not available. STUDY DESIGN AND METHODS: The sensitivity of an HIV-1/2 recombinant strip immunoblot assay (SIA) for HIV-2 was determined on the basis of the analysis of 65 HIV-2-positive samples identified by the Centers for Disease Control and Prevention (CDC). Anti-HIV-1/2 combination EIA-repeatably reactive (RR) specimens from seven blood centers and their affiliated hospitals were tested in parallel by HIV-1 WB and HIV-2 EIA. Anti-HIV-2 EIA-RR specimens were further tested by HIV-1/2 SIA. Specimens interpreted as positive for HIV-2 or HIV-1/2 were referred to the CDC for final resolution of antibody status. RESULTS: Ninety-seven percent (63/65) of known HIV-2-positive samples tested positive for HIV-2 only or HIV-1/2 on the HIV-1/2 SIA. A total of 1048 anti-HIV-1/2 combination-EIA-RR specimens were evaluated. Sixty-nine percent (75/109) of the WB-positive specimens were HIV-2 EIA-RR, while only 9 percent (84/939) of WB-indeterminate or WB-negative specimens tested HIV-2 EIA-RR. The HIV-1/2 SIA resolved 91 percent of HIV-2 EIA-RR samples as negative. Four HIV-2 EIA-RR specimens (all HIV-1 WB-positive) were classified as positive for HIV-1 and HIV-2 in the HIV-1/2 SIA. Final interpretation of these specimens by CDC was that they were reactive for HIV-1 with cross-reactivity to HIV-2. CONCLUSION: No confirmed HIV-2-positive specimens were detected. The HIV-1/2 SIA is currently useful for resolving HIV-2 EIA-RR specimens.

AIDS Serodiagnosis↗
PubMed1998

Longitudinal study of plasma HIV-1 RNA concentrations during the asymptomatic stage of HIV infection measured using AMPLICOR HIV monitor and NASBA HIV-1 RNA QT tests. ACCTES Association.

The predictive value of two methods for measuring HIV RNA concentration in plasma was assessed in relation to CD4 lymphocyte counts during the asymptomatic period of infection. The design was a retrospective longitudinal case-control study for a mean period of 60 months involving 20 asymptomatic patients included in the French National prospective survey. The CD4 counts in these patients during the last 36 months of the study were stable (non-progressors) or declined (progressors). Plasma RNA concentrations were determined in each subject annually using the AMPLICOR and NASBA techniques. Only AMPLICOR gave RNA titers above the cut-off value for all the patients. The techniques agreed satisfactorily, although there was a difference, median 0.4 log10, between the AMPLICOR and NASBA values. The non-progressors had low and stable RNA concentrations. The concentration was higher in the progressors, according to the AMPLICOR technique, from their inclusion in the study, and according to the NASBA technique, from 1 year after inclusion. However, only four of ten individual progressors had stable plasma HIV RNA concentrations significantly above those of the non-progressors before the decline in their CD4 counts. These were all and only the patients with a decline in lymphocyte counts more than 100 CD4/mm3/year. In each of the other progressors, the RNA concentration was not significantly different from those of the non-progressors. Thus, when making decisions about therapy, plasma HIV RNA determinations cannot be used in place of CD4 counts and may provide valuable additional information.

CD4 Lymphocyte Count↗
PubMed2001

[Evaluation of an HIV screening assay kit for the combined detection of anti-HIV-1/2 antibodies and HIV p24 antigen].

We have evaluated a new HIV screening assay kit (Genscreen HIV Ag-Ab) for the HIV antigen-antibody combined test by comparing with two HIV antigen-antibody combined assay kits (VIDAS HIV DUO, Enzygnost HIV integral). Genscreen HIV Ag-Ab is a microwell plate enzyme immunoassay for the detection of HIV infection, based on the detection of anti-HIV-1/2 antibodies and HIV p24 antigen in human serum or plasma. In this study, 90 samples of HIV-1 antibody positive sera and 670 samples of HIV negative sera were examined. The sensitivity was 100% and the specificity was 99.7%. All of HIV-1 group M sera (subtypes A to G and B/D), HIV-1 group O sera and HIV-2 sera in worldwide HIV performance panel-302 were positive with Genscreen HIV Ag-Ab. Ten commercially available HIV-1 seroconversion panels were tested to evaluate sensitivity of three HIV antigen-antibody combined assay kits. Genscreen HIV Ag-Ab detected infection at the same bleeds as VIDAS HIV DUO in 8 of 10 seroconversion panels and 1 to 2 bleeds earlier than Enzygnost HIV integral in 5 of 10 seroconversion panels. However, VIDAS HIV DUO indicated false negative on 5th bleed in panel BB (PRA952). The result of the specimen was positive on 3rd bleed, equivocal on 4th bleed, negative on 5th bleed and again positive on 6th bleed. All of these specimens were positive by Genscreen HIV Ag-Ab. Therefore, Genscreen HIV Ag-Ab that shorten the window period is a useful and reliable for HIV screening test, especially in case of primary infection.

AIDS Serodiagnosis↗
PubMed2006

Lower levels of HIV RNA in semen in HIV-2 compared with HIV-1 infection: implications for differences in transmission.

BACKGROUND AND OBJECTIVES: HIV-2 infection, in comparison with HIV-1, is characterized by lower plasma viral loads, slower CD4 cell count decline, decreased AIDS-related mortality, and lower rates of mother-to-child and sexual transmission. To gain further insight into why HIV-1 is more readily transmitted as compared with HIV-2, we analyzed semen and plasma HIV RNA levels in HIV-1 and HIV-2-positive men from Senegal. DESIGN AND METHODS: Twenty-two HIV-1 and 10 HIV-2-infected subjects from the University of Dakar donated semen and blood samples for this analysis. HIV-1 and HIV-2 viral loads in semen and plasma were quantified using type-specific polymerase chain reaction assays. RESULTS: The mean age of the subjects was 37 and 40 years; mean CD4 cell count was 222 and 276 cells/microl and the mean plasma viral load was 4.7 and 3.0 log10 copies/ml for HIV-1 and HIV-2, respectively (P = 0.002). HIV RNA was detected in semen in 21 of 22 (95%) of HIV-1 and seven of 10 (70%) of HIV-2-infected subjects; P = 0.07). However, the levels of HIV RNA present in semen were markedly different between those with HIV-1 and HIV-2, with a mean of 4.4 log10 copies/ml among those with HIV-1 and a mean of 2.6 log10 copies/ml among those with HIV-2 (P < 0.001). In multivariate analysis, plasma viral load and HIV type, but not CD4 cell count, were independently predictive of semen viral load (P = 0.03, 0.05, 0.48, respectively) CONCLUSIONS: These data suggest that differences in semen viral load between HIV-1 and HIV-2 may be in part responsible for the markedly different transmission rates of these two viruses. In addition, risk of male genital tract shedding strongly correlates with plasma viral loads. Interventions that decrease viral load may help decrease transmission of both HIV-1 and HIV-2.

Adult↗
PubMed2003

Missed opportunities for perinatal HIV prevention among HIV-exposed infants born 1996-2000, pediatric spectrum of HIV disease cohort.

OBJECTIVE: Despite dramatic reductions in perinatal human immunodeficiency virus (HIV) transmission in the United States, obstacles to perinatal HIV prevention that include lack of prenatal care; failure to test pregnant women for HIV before delivery; and lack of prenatal, intrapartum, or neonatal antiretroviral (ARV) use remain. The objective of this study was to describe trends in perinatal HIV prevention methods, perinatal transmission rates, and the contribution of missed opportunities for perinatal HIV prevention to perinatal HIV infection. METHODS: We analyzed data obtained from infant medical records on 4755 HIV-exposed singleton deliveries in 1996-2000, from 6 US sites that participate in the Centers for Disease Control and Prevention's Pediatric Spectrum of HIV Disease Project. HIV-exposed deliveries refer to deliveries in which the mother was known to have HIV infection during the pregnancy. RESULTS: Of the 4287 women with data on prenatal care, 92% had prenatal care. From 1996 to 2000, among the 3925 women with prenatal care, 92% had an HIV test before delivery; the use of prenatal zidovudine (ZDV) alone decreased from 71% to 9%, and the use of prenatal ZDV with other ARVs increased from 6% to 70%. Complete data on maternal and neonatal ARVs were available for 3284 deliveries. Perinatal HIV transmission was 3% in 1651 deliveries with prenatal ZDV in combination with other ARVs, intrapartum ZDV, and neonatal ZDV; 6% in 1111 deliveries with prenatal, intrapartum, and neonatal ZDV alone; 8% in 152 deliveries with intrapartum and neonatal ZDV alone; 14% of 73 deliveries with neonatal ZDV only started within 24 hours of birth; and 20% in 297 deliveries with no prenatal, intrapartum, and neonatal ARVs. Complete data on prenatal events were available in 328 HIV-infected and 3258 HIV-uninfected infants. A total of 56% of mothers of HIV-infected infants had missed opportunities for perinatal HIV prevention versus 16% of mothers of HIV-uninfected infants. Forty-four percent of the infected infants were born to mothers who had prenatal care, a prenatal HIV diagnosis, and documented prenatal ARV therapy. Seventeen percent of women with reported illicit drug use had no prenatal care versus 3% of women with no reported drug use. In a multivariate analysis, maternal illicit drug use was significantly associated with lack of prenatal care. In a multivariate analysis, year of infant birth and the combination of lack of maternal HIV testing before delivery and lack of prenatal antiretroviral therapies were significantly associated with perinatal HIV transmission. CONCLUSIONS: Missed opportunities for perinatal HIV prevention contributed to more than half of the cases of HIV-infected infants. Prenatal care and HIV testing before delivery are major opportunities for perinatal HIV prevention. Illicit drug use was highly associated with lack of prenatal care, and lack of HIV testing before delivery was highly associated with perinatal HIV transmission.

Anti-HIV Agents↗
PubMed1998

Rapid assay for simultaneous detection and differentiation of immunoglobulin G antibodies to human immunodeficiency virus type 1 (HIV-1) group M, HIV-1 group O, and HIV-2.

A rapid immunodiagnostic test that detects and discriminates human immunodeficiency virus (HIV) infections on the basis of viral type, HIV type 1 (HIV-1) group M, HIV-1 group O, or HIV-2, was developed. The rapid assay for the detection of HIV (HIV rapid assay) was designed as an instrument-free chromatographic immunoassay that detects immunoglobulin G (IgG) antibodies to HIV. To assess the performance of the HIV rapid assay, 470 HIV-positive plasma samples were tested by PCR and/or Western blotting to confirm the genotype of the infecting virus. These samples were infected with strains that represented a wide variety of HIV strains including HIV-1 group M (subtypes A through G), HIV-1 group O, and HIV-2 (subtypes A and B). The results showed that the HIV genotype identity established by the rapid assay reliably (469 of 470 samples) correlates with the HIV genotype identity established by PCR or Western blotting. A total of 879 plasma samples were tested for IgG to HIV by a licensed enzyme immunoassay (EIA) (470 HIV-positive samples and 409 HIV-negative samples). When they were tested by the rapid assay, 469 samples were positive and 410 were negative (99.88% agreement). Twelve seroconversion panels were tested by both the rapid assay and a licensed EIA. For nine panels identical results were obtained by the two assays. For the remaining three panels, the rapid assay was positive one bleed later in comparison to the bleed at which the EIA was positive. One hundred three urine samples, including 93 urine samples from HIV-seropositive individuals and 10 urine samples from seronegative individuals, were tested by the rapid assay. Ninety-one of the ninety-three urine samples from HIV-seropositive individuals were found to be positive by the rapid assay. There were no false-positive results (98.05% agreement). Virus in all urine samples tested were typed as HIV-1 group M. These results suggest that a rapid assay based on the detection of IgG specific for selected transmembrane HIV antigens provides a simple and reliable test that is capable of distinguishing HIV infections on the basis of viral type.

HIV Antibodies↗
PubMedDate not supplied

Low peripheral blood viral HIV-2 RNA in individuals with high CD4 percentage differentiates HIV-2 from HIV-1 infection.

OBJECTIVES: To elucidate why the virulence of HIV-1 and HIV-2 infections differ in West African populations. STUDY DESIGN/METHOD: Peripheral blood plasma virion RNA and cellular proviral DNA levels were measured in a cross-section of 59 HIV-1 and 49 HIV-2 singly infected individuals representing all stages of infection in The Gambia, West Africa. Novel reverse transcriptase polymerase chain reaction (RT-PCR) assays specific and sensitive for virus quantification of non-clade B HIV-1 and HIV-2 infections were used. RESULTS: HIV-1 and HIV-2 proviral and plasma RNA levels were inversely correlated with CD4+ count for both infections with cellular proviral load similar at each stage of infection. Critically, up to three-fourths of HIV-2-infected individuals with high CD4 percentages (> 28%) had undetectable (< 500 copies/mL) levels of peripheral blood HIV-2 RNA in contrast to HIV-1-infected individuals who had readily detectable plasma virus at all stages of infection (P < .0001). Plasma RNA levels were similar in the intermediate and end stages of infection, indicating similar replication potential for both viruses. In the cross-section of HIV-1- and HIV-2-infected patients studied, the data indicate a wider dynamic range of HIV-2 RNA in vivo compared with HIV-1. DISCUSSION: Low levels of HIV-2 replication and virion expression characterize individuals with high CD4+ lymphocyte counts, suggesting that a very different dynamic equilibrium exists between virus and host for HIV-2 compared with HIV-1. By analogy with HIV-1, our data implicate a considerably lower turnover of HIV-2 virion RNA in vivo with a markedly reduced production of infectious genomes in individuals during the subclinical phase of infection. CONCLUSION: The lower levels of virion expression of HIV-2 infections in vivo are compatible with observed differences in the natural history of HIV-1 and HIV-2 infections, relating to overall differences in the pathogenesis and disease progression of the two infections.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Comparison of human immunodeficiency virus (HIV)-specific T-cell responses in HIV-1- and HIV-2-infected individuals in Senegal.

Human immunodeficiency virus type 2 (HIV-2) infection is typically less virulent than HIV-1 infection, which may permit the host to mount more effective, sustained T-cell immunity. We investigated antiviral gamma interferon-secreting T-cell responses by an ex vivo Elispot assay in 68 HIV-1- and 55 HIV-2-infected Senegalese patients to determine if differences relate to more efficient HIV-2 control. Homologous HIV-specific T cells were detected in similar frequencies (79% versus 76%, P = 0.7) and magnitude (3.12 versus 3.08 log(10) spot-forming cells/10(6) peripheral blood mononuclear cells) in HIV-1 and HIV-2 infection, respectively. Gag-specific responses predominated in both groups (>/=64%), and significantly higher Nef-specific responses occurred in HIV-1-infected (54%) than HIV-2-infected patients (22%) (P < 0.001). Heterologous responses were more frequent in HIV-1 than in HIV-2 infection (46% versus 27%, P = 0.04), but the mean magnitude was similar. Total frequencies of HIV-specific responses in both groups did not correlate with plasma viral load and CD4(+) T-cell count in multivariate regression analyses. However, the magnitude of HIV-2 Gag-specific responses was significantly associated with lower plasma viremia in HIV-1-infected patients (P = 0.04). CD4(+) T-helper responses, primarily recognizing HIV-2 Gag, were detected in 48% of HIV-2-infected compared to only 8% of HIV-1-infected patients. These findings indicate that improved control of HIV-2 infection may relate to the contribution of T-helper cell responses. By contrast, the superior control of HIV-1 replication associated with HIV-2 Gag responses suggests that these may represent cross-reactive, higher-avidity T cells targeting epitopes within Gag regions of functional importance in HIV replication.

Adolescent↗
PubMed2006

Quantification of genital human immunodeficiency virus type 1 (HIV-1) DNA in specimens from women with low plasma HIV-1 RNA levels typical of HIV-1 nontransmitters.

Studies of human immunodeficiency virus type 1 (HIV-1) transmission suggest that genital HIV-1 RNA and DNA may both be determinants of HIV-1 infectivity. Despite its potential role in HIV-1 transmission, there are limited quantitative data on genital HIV-1 DNA. Here we validated an in-house real-time PCR method for quantification of HIV-1 DNA in genital specimens. In reactions with 100 genomes to 1 genome isolated from a cell line containing one HIV-1 provirus/cell, this real-time PCR assay is linear and agrees closely with a commercially available real-time PCR assay specific for a cellular housekeeping gene. In mock genital samples spiked with low numbers of HIV-1-infected cells such that the expected HIV-1 DNA copy number/reaction was 100, 10, or 5, the average copy number/reaction was 80.2 (standard deviation [SD], 28.3), 9.1 (SD, 5.4), or 3.1 (SD, 2.1), respectively. We used this method to examine genital HIV-1 DNA levels in specimens from women whose low plasma HIV-1 RNA levels are typical of HIV-1 nontransmitters. The median HIV-1 DNA copy number in endocervical secretions from these women (1.8 HIV-1 DNA copies/10,000 cells) was lower than that for women with higher plasma HIV-1 RNA levels (16.6 HIV-1 DNA copies/10,000 cells) (P=0.04), as was the median HIV-1 DNA copy number in vaginal secretions (undetectable versus 1.0 HIV-1 DNA copies/10,000 cells). These data suggest that women with low plasma HIV-1 RNA and thus a predicted low risk of HIV-1 transmission have low levels of genital HIV-1 cell-associated virus. The assay described here can be utilized in future efforts to examine the role of cell-associated HIV-1 in transmission.

Adult↗
PubMed1996

Frequency of human immunodeficiency virus (HIV) infection among contemporary anti-HIV-1 and anti-HIV-1/2 supplemental test-indeterminate blood donors. The Retrovirus Epidemiology Donor Study.

BACKGROUND: Follow-up studies from the mid-1980s showed that 1 to 5 percent of blood donors testing reactive in anti-human immunodeficiency virus type 1 (HIV-1) enzyme immunoassay (EIA) and testing indeterminate in Western blot were infected with HIV-1 and were in the process of seroconverting. The present study was conducted to establish the rate of HIV infection among contemporary anti-HIV-1/HIV type 2 (HIV-2) EIA-reactive, Western blot-indeterminate donors. STUDY DESIGN AND METHODS: Donations (n = 607) with indeterminate HIV supplemental test results were identified by screening 3,021,342 donations given from November 1990 through August 1993 at five participating blood centers. Consenting donors were enrolled and samples taken 4 to 8 weeks after donation. Follow-up sera were tested by EIA and Western blot for anti-HIV-1 seroconversion and by type-specific peptide assays for antibodies to HIV-2 and HIV-1 subtype O. Peripheral blood mononuclear cells and/or plasma from the follow-up samples were tested for HIV-1 DNA and/or RNA by polymerase chain reaction. The rate of HIV-1 infection among Western blot-indeterminate donors was also estimated by multiplying the incidence rate of HIV-1 seroconversion in this donor population by the estimated duration of the EIA-reactive and Western blot-indeterminate window during seroconversion (8.5 days). RESULTS: Supplemental test-indeterminate donors (n = 355) enrolled a median of 38 days after donation; 265 (75%) of these donors were identified as indeterminate after an anti-HIV-1/2 EIA-reactive donation. Enrolled and non-enrolled donors had similar distributions of demographic characteristics and band patterns. Follow-up samples from all 355 donors tested negative for HIV-1 in polymerase chain reaction. Follow-up sera tested Western blot-negative in 54 cases (15%) and Western blot-indeterminate in 299 (84%). Two follow-up sera (0.6%) were interpreted, according to manufacturer's package insert criteria, as Western blot positive with p24 and gp41 bands and/or gp120/160 bands; however, paired testing of index and follow-up sera from these two cases showed identical Western blot and EIA reactivity, and polymerase chain reaction was negative for HIV RNA and DNA, which ruled out HIV infection. The absence of HIV infection in 355 Western blot-indeterminate donors was consistent with our incidence-based model analysis, which yielded an estimate of one HIV-1 infection for every 215 Western blot-indeterminate donations (95% CI, 1/39-1/8333). CONCLUSION: Contemporary blood donors classified as indeterminate in supplemental HIV testing are infrequently infected with HIV. Donors whose follow-up samples test negative in anti-HIV-1/2 EIAs and negative or persistently indeterminate in Western blots should be considered eligible for reinstatement.

Adult↗
PubMed1995

HIV status of female sex partners of men reactive to HIV-1, HIV-2 or both viruses in Abidjan, Côte d'Ivoire.

OBJECTIVES: To compare rates of serologic concordance in the female sex partners of men with HIV-1 and HIV-2 infections, and to determine the serologic status of sex partners of men who reacted serologically to both viruses. DESIGN: Cross-sectional study. SETTING: Infectious diseases service in a University Hospital in Abidjan, Côte d'Ivoire (West Africa). PARTICIPANTS: Hospitalized men reactive on synthetic peptide-based tests to HIV-1, HIV-2 or both viruses (dually reactive), and their spouses visiting them in hospital. OUTCOME MEASURES: Serologic status of female spouses of seropositive men. RESULTS: The serologic status of 540 spouses of 490 HIV-1- and/or HIV-2-positive, hospitalized men was studied. Similar proportions of spouses of HIV-1-infected men (49%) and HIV-2-infected men (44%) were concordantly seropositive. The overall prevalence of infection in spouses of dually reactive men (72%) was significantly higher than in spouses of other men; 44% of these spouses were infected with HIV-1, 8% with HIV-2, and 20% were themselves dually reactive. Considering only the seropositive female spouses of men monotypically reactive to HIV-1 or HIV-2, and the male spouses of women monotypically infected, rates of serologic discordance were significantly greater in men (24%) than women (7%). CONCLUSIONS: Men were likely to have been infected earlier than women because of their HIV-associated illness; also, men more frequently had serologic profiles indicative of infection outside of the union. Rates of serologic concordance in spouses of men with advanced HIV-1 or HIV-2 infection were similar (44-49%). Dually reactive hospitalized men frequently (72%) had seropositive sex partners, most of whom were HIV-1-positive. Dual reactivity was also frequent in these spouses, suggesting transmission of both HIV-1 and HIV-2, or of a cross-reactive strain, and a minority of partners were infected with HIV-2 alone. Prospective studies of discordant couples using quantitative molecular diagnostic techniques are required for better understanding of dual reactivity and transmission of HIV-1 and HIV-2.

Adolescent↗
PubMed2001

Prevalence and risk factors of cervicovaginal HIV shedding among HIV-1 and HIV-2 infected women in Dakar, Senegal.

OBJECTIVES: To assess the risk determinants and prevalence of cervicovaginal shedding of HIV-1 and HIV-2 among women in Dakar, Senegal. METHODS: We conducted a cross sectional study of 153 HIV seropositive female sex workers (FSW) and another 142 HIV seropositive women attending an infectious diseases unit, based on an interview, physical examination, and laboratory screening for major sexually transmitted infections (STI). Cervicovaginal lavage fluid was tested for HIV-RNA by means of nested PCR. Links between cervicovaginal shedding of HIV-1 and HIV-2 and sociodemographic, clinical, and laboratory variables were identified by using odd ratios and 95% confidence intervals. Logistic regression analysis was used to identify independent links with HIV shedding. RESULTS: The detection rate of HIV-RNA in cervicovaginal lavage fluid was low among FSW, with no difference between HIV-1 (7/90: 8%) and HIV-2 (3/48: 6%). The rate was far higher among the other women (41%, 48/117; 33%, 7/21 for HIV-1 and HIV-2, respectively). In multivariate analysis, high plasma viral load (>40 000 copies/ml) (AOR = 2.4 (1.0-5.6) p = 0.04) and basic vaginal pH (AOR = 2.2 (1.3-3.7) p = 0.002) were independently associated with HIV-1 shedding. For HIV-2 a CD4 count < 200 cells x 10(6)/l was the only factor associated with the shedding of HIV-2 (AOR = 9.0 (0.9-93)). The genital shedding rate was higher with HIV-1 than with HIV-2 (OR = 2.1 (0.9-4.8), but this difference disappeared after adjustment for the CD4+ cell count (AOR = 1.2 (0.5-2.9)). CONCLUSION: Advanced disease stage and immunosuppression are the major risk determinants for shedding of both HIV-1 and HIV-2. Basic vaginal pH is also a risk determinant for HIV-1 shedding.

Adult↗
PubMed1993

Second exon of Tat of HIV-2 is required for optimal trans-activation of HIV-1 and HIV-2 LTRs.

To determine conditions for optimal trans-activation by Tat of HIV-2, genomic DNAs and cDNAs encoding Tat of HIV-2 were tested on their homologous (HIV-2) and heterologous (HIV-1) long terminal repeats (LTRs). It has been previously reported that Tat of HIV-2 could efficiently trans-activate only its own LTR but not that of HIV-1. The inefficient trans-activation of HIV-1 is due, in part, to an acidic residue in the basic, RNA-binding domain of Tat of HIV-2. Here we demonstrate that inefficient trans-activation of HIV-1 LTR is observed only with plasmids that express exon 1 and genomic forms of tat of HIV-2. Expression of both exons of Tat of HIV-2 from cDNA results in trans-activation of HIV-1 that is equivalent to the effect of Tat of HIV-1. In addition, the cDNA form of tat of HIV-2 trans-activates the HIV-2 LTR more efficiently than exon 1 and genomic forms of tat of HIV-2. We conclude that exon 2 of Tat of HIV-2 is important for optimal interactions with the trans-acting responsive regions (TARs) of HIV-1 and HIV-2 and that differential expression of short and full-length Tats of HIV-2 during the viral life cycle might affect viral latency, levels of viral replication, and cellular cytopathology.

Amino Acid Sequence↗
PubMed1998

Characterization of HIV-1-specific antibodies and HIV-1-crossreactive antibodies to platelets in HIV-1-infected haemophiliac patients.

Sera from HIV-1-infected haemophiliacs were examined for human immunodeficiency virus (HIV) specific antibodies and for platelet crossreactive antibodies. Using HIV sepharose 4B affinity columns for serum absorption, antibodies against various HIV antigens, including HIV lysate. HIV-p24 and HIV-gp120, were eluted either by low or by high pH buffer. The eluates were examined by ELISA for HIV specificity and by flow cytometry for platelet crossreactivity. Two types of HIV antibodies could be eluted, i.e. acid-sensitive and alkaline-sensitive antibodies. HIV antibodies were obtained in 26/29 acid eluates and in 25/29 of the alkaline eluates from HIV-lysate columns; 96% (25/26) of the acid-eluted antibodies were HIV-specific but 48% (12/ 25) of the alkaline-eluted antibodies also showed crossreactivity to platelets. Of the 20 alkaline-eluted HIV-p24 antibodies, 40% (8/20) reacted specifically with HIV-p24 and 60% (12/20) were platelet crossreactive. In contrast, of the alkaline-eluted HIV-gp120 antibodies (n=17), 88% (15/17) were HIV gp120-specific and only 12% (2/17) were platelet crossreactive. Western blot analysis of platelets demonstrated that the anti-p24 antibodies recognized three bands with approximate molecular weights of 72000 to 95000. 69% of the serum antiplatelet antibodies showed platelet glycoprotein IIbIIIa specificity. Anti-HIV antibodies could be eluted from platelets. Hence, platelet crossreactive antibodies in HIV infection are primarily alkaline-sensitive and are associated predominantly with HIV p24 antibody; these antibodies may play a role in the immune thrombocytopenia of HIV-infected haemophiliacs.

Acquired Immunodeficiency Syndrome↗