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PubMed1990

Discrimination between HIV-1 and HIV-2-seropositive individuals using mouse monoclonal antibodies directed to HIV transmembrane proteins.

Mouse monoclonal antibodies directed against the transmembrane proteins of HIV-1 or HIV-2 provided site-directed, unambiguous discrimination between HIV-1 and HIV-2 antibody-positive sera, when employed in immunoassays as competitive probes against serum antibodies. These monoclonal antibodies mapped to epitopes outside of the well-characterized immunodominant regions (IDR) of the transmembrane proteins. The monoclonal competitive immunoassay was a superior method for discrimination compared with immunoprecipitation of metabolically radiolabeled HIV envelope glycoproteins, Western blot against viral envelope glycoproteins, or noncompetitive enzyme immunoassays employing HIV recombinant transmembrane proteins or synthetic IDR peptides as serological targets. The monoclonal competitive assay was not affected by antigenic cross reactivity or nonspecific reactivity exhibited by selected serum samples toward envelope proteins or peptides, respectively. Results of the monoclonal competitive immunoassay were supported by results of a peptide inhibition assay employing free IDR peptides in competition with IDR peptides on a solid support for binding of serum antibody. IDR peptide inhibition clearly demonstrated non-cross-reactive antigenic specificity of sera toward either the HIV-1 IDR or the HIV-2 IDR. The monoclonal competitive assay also identified samples containing antibody to both HIV-1 and HIV-2 transmembrane proteins. Analysis of these samples by IDR peptide inhibition indicated they contained two distinct, non-cross-reactive populations of antibodies, one directed to the HIV-1 IDR and the other directed to the HIV-2 IDR.

AIDS Serodiagnosis↗
PubMed2000

HIV-1-Specific CD4 helper function in persons with chronic HIV-1 infection on antiviral drug therapy as measured by ELISPOT after treatment with an inactivated, gp120-depleted HIV-1 in incomplete Freund's adjuvant.

OBJECTIVE: We hypothesized that treatment of HIV-1-seropositive study subjects receiving potent antiviral therapy with an HIV-specific immune-based therapy would increase HIV-1-specific T-helper immune function. DESIGN: 10 HIV-1-seropositive study subjects receiving antiretroviral therapy were treated with an inactivated, gp120-depleted immunogen in IFA (HIV-1 immunogen, Remune) at baseline, week 12, and week 24. METHODS: The frequency of HIV-1 antigen-stimulated interferon-gamma (IFN-gamma)-producing cells was determined by the ELISPOT assay. RESULTS: Study subjects significantly increased their frequency of HIV-1-stimulated (p <. 001) or p24 antigen-stimulated (p <.01) IFN-gamma-producing cells after one, two, and three treatments of HIV-1 immunogen. Depletion of CD4 cells resulted in the strongest abrogation of the IFN-gamma response. The frequency of HIV-1 (r = 0.64; p =.0002) and p24 (r = 0. 72; p <.001) antigen-stimulated IFN-gamma-producing cells in the CD8-depleted population before and after treatment was associated with the lymphocyte-proliferative response. CONCLUSIONS: Treatment with HIV-1 immunogen significantly enhanced the frequency of HIV-1-specific IFN-gamma-producing cells. Studies are ongoing to determine the relationship between this reversal of HIV-specific anergy and virologic outcomes.

AIDS Vaccines↗
PubMed1998

A critical assessment of the prognostic value of HIV-1 RNA levels and CD4+ cell counts in HIV-infected patients. The Swiss HIV Cohort Study.

OBJECTIVE: To determine to what extent human immunodeficiency type 1 (HIV-1) RNA levels and CD4+ cell counts predict clinical outcomes in a general HIV-1-infected population. METHODS: Community-based prospective study (Swiss HIV Cohort Study) including 394 HIV-1-infected patients, randomly selected from 4 strata of CD4+ cell counts (0 to < 0.05, 0.05 to < 0.20, 0.20 to < 0.50, and > or = 0.50 x 10(9)/L). Levels of HIV-1 RNA, CD4+ cell counts, and other variables were evaluated from samples collected between 1991 and 1993 for their ability to predict death and clinical progression. RESULTS: Patients were followed up on average for 29 months. Baseline HIV-1 RNA levels, CD4+ cell counts, clinical stage, and beta 2-microglobulin levels independently predicted survival, whereas only HIV-1 RNA levels and CD4+ cell counts independently predicted clinical progression. Multivariate relative hazards (RHs) for death ranged from 1.0 to 5.4 across quartiles of CD4+ counts, but only from 1.0 to 1.8 across quartiles of HIV-1 RNA. For clinical progression, gradients of risk were similar for CD4+ counts (1.0-4.2) and for HIV-1 RNA (1.0-3.1). In patients with CD4+ cell counts less than 0.05 x 10(9)L, HIV-1 RNA levels predicted neither death nor clinical progression. Finally, the number of HIV-1 RNA copies per CD4+ cell was the best predictor of death (multivariate RH, 1.0-9.7 across quartiles) and clinical progression (multivariate RH, 1.0-4.1). CONCLUSIONS: Levels of HIV-1 RNA and CD4+ cell counts provided independent and complementary information on clinical outcomes. The RNA/CD4+ ratio was the best single predictor. In patients who had fewer than 0.05 x 10(9)/L CD4+ cells, HIV-1 RNA levels had little prognostic value.

Adult↗
PubMed1998

Detection of HIV-RNA-positive monocytes in peripheral blood of HIV-positive patients by simultaneous flow cytometric analysis of intracellular HIV RNA and cellular immunophenotype.

Determinations of plasma HIV viral RNA copy numbers help to define the kinetics of HIV-1 infection in vivo and to monitor antiretroviral therapy. However, questions remain regarding the identity of various infected cell types contributing to this free virus pool and to the in vivo lifecycle of HIV during disease progression. Characterization of a novel fluorescence in situ hybridization (FISH) assay employing a pool of labeled oligonucleotide probes directed against HIV RNA was done followed by coupling of the FISH assay with simultaneous surface immunophenotyping to address these questions. In vitro characterizations of this assay using tumor necrosis factor-alpha stimulated and unstimulated ACH-2 cells demonstrated the ability to detect < 5% HIV RNA positive cells with a sensitivity of < 30 RNA copies per cell. Peripheral blood mononuclear cells from 39 HIV-seropositive patients on no, single, combination, or triple drug therapy and 8 HIV-seronegative patients were examined. The majority of HIV-positive patients (24/39) harbored monocytes positive for HIV RNA and a significantly higher fraction of patients with high plasma viral load carried positive monocytes (13/16) than did patients in the low plasma viral load group (11/23). These results demonstrate the effectiveness of a novel FISH assay for identifying and monitoring HIV-infected cell populations in the peripheral blood of HIV-positive patients. In addition, monocytes are a major source of cellular HIV virus in the peripheral blood of HIV patients, even with progression of disease.

Cell Line↗
PubMed1990

Bacterially produced HIV-2 env polypeptides specific for distinguishing HIV-2 from HIV-1 infections.

Five unique recombinant polypeptides, each encoded by a DNA segment representing a different region of the HIV-2 (NIH-Z strain) env gene, were produced at relatively high levels (greater than or equal to 5%) as cII-fusion products in Escherichia coli. These recombinant polypeptides were characterized serologically by the Western blot assay against a panel of HIV-2 and HIV-1 antibody-positive sera, and with normal human sera (HIV-1 and HIV-2 antibody negative). Only those polypeptides that are encoded by a segment of the env gene from the N-terminal region of the transmembrane protein gp35 (amino acids 537 to 707) were immunoreactive. Three polypeptides (921, 996, and 997), each encoding this immunoreactive region of the HIV-2 (NIH-Z) gp35, reacted strongly and specifically with antibodies in sera from HIV-2-positive individuals, but not with antibodies in sera from HIV-1-positive or HIV-uninfected individuals. These results show that the N-terminal region of the HIV-2 gp35 contains a highly antigenic determinant which is strongly immunogenic in HIV-2-infected individuals. The gp35-encoded recombinant env polypeptides can potentially be used in diagnostic assays to specifically differentiate between HIV-2 and HIV-1 infections.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Early detection of perinatal human immunodeficiency virus (HIV) type 1 infection using HIV RNA amplification and detection. New York City Perinatal HIV Transmission Collaborative Study.

Early diagnosis of perinatally transmitted human immunodeficiency virus type 1 (HIV) infection can guide early interventions. HIV coculture and DNA polymerase chain reaction (DNA-PCR) detect few HIV-infected infants at birth and 90%-100% by age 3 months. Because extracellular HIV RNA may appear soon after infection, a plasma HIV RNA assay was compared with DNA-PCR for early detection of perinatally infected infants. Blood-draw specimens (108) obtained at the same time from 49 HIV-infected infants and 10 specimens from 8 uninfected infants were tested. HIV RNA and DNA-PCR positivity rates were 56% and 33%, respectively, in 36 specimens from 36 infants <28 days of age (binomial test, P = .001). Among 81 specimens obtained after age 14 days, 79 (98%) were positive by HIV RNA testing. No HIV-infected infant specimens were DNA-PCR-positive and HIV RNA-negative. All specimens from 8 uninfected infants were HIV RNA-negative. These results suggest that plasma HIV RNA was detectable earlier and more reliably than HIV DNA in perinatal infection.

Female↗
PubMed2000

Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children < or = 5 years of age, Pediatric Spectrum of HIV Disease project (PSD), USA.

BACKGROUND: In response to recent reports of mitochondrial dysfunction in HIV-uninfected infants exposed to antiretroviral (ARV) prophylaxis, the Perinatal Safety Review Working Group reviewed deaths in five large HIV-exposed perinatal cohorts in the United States to determine if similar cases of severe mitochondrial toxicity could be detected. We describe the results of this review for the PSD cohort. METHODS: Hospitalization, clinic and death records for deceased HIV-uninfected and HIV-indeterminate children who were less than 5 years of age were reviewed. Standard definitions were used to classify HIV infection status and the likelihood that signs and symptoms were related to mitochondrial dysfunction. Children were classified as having signs and symptoms that were considered (1) unrelated, (2) unlikely, (3) consistent with, or (4) likely related to mitochondrial disease. SIDS deaths were put into a separate category. RESULTS: 8,465 of 13,125 HIV-exposed children were either HIV-uninfected or HIV-indeterminate. Among the 84 deaths in the subgroup of 8,465 children, 9 were considered in Class 2 (unlikely), 4 were considered in Class 3 (consistent with), and none were considered in Class 4 (likely). 97% of those children who received ARV prophylaxis received zidovudine alone. None of the HIV-uninfected deaths were classified in 2, 3, or 4; and only one of these was exposed to ARV prophylaxis. Among the 3 HIV-indeterminate children who were classified in 3 (consistent with), 2 had no or unknown ARV exposure before 1994 when use of ZDV prophylaxis became the standard of care. Both HIV-uninfected and HIV-indeterminate children with ARV exposure or unknown exposure had lower mortality rates than children without ARV exposure. CONCLUSION: Monoprophylaxis with ZDV was not associated with higher death rates in the cohort of 8,465 children or with any findings likely consistent with mitochondrial dysfunction among the 85 deaths. Ongoing monitoring of drug safety in large multi-site prospective cohort studies of HIV-exposed children is essential in the era of highly active antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Comparative evaluation of NASBA HIV-1 RNA QT, AMPLICOR-HIV monitor, and QUANTIPLEX HIV RNA assay, three methods for quantification of human immunodeficiency virus type 1 RNA in plasma.

Three commercial assays for quantifying plasma human immunodeficiency virus type 1 (HIV-1) RNA were evaluated. The assays differed in their sample volumes, the means of preparing samples, and methods of amplification and detection. Plasma samples were obtained from 36 HIV-1-infected patients representing all stages of HIV-1 infection and were analyzed as coded specimens. Measurement of HIV-1 RNA baseline levels revealed no significant difference in sensitivity between the three assays. The assays were also applied to the quantitation of HIV-1 RNA levels in the plasma of patients who were changing their antiretroviral therapy. The changes measured in HIV-1 RNA levels in plasma in response to therapy were comparable by the three assays. No close correlation was found between the amount of HIV-1 RNA and the CD4 T-cell count; HIV-1 RNA assays were more sensitive than p24 antigen assays as an indicator of plasma viremia. Overall, the study demonstrates that all three quantitative assays for HIV-1 RNA can be used to measure the HIV-1 RNA copy number representing the HIV-1 viremia status in patients with HIV-1 infection. Since this copy number is likely to be useful in monitoring the effectiveness of antiviral therapy, these quantitative assays for HIV-1 RNA are ready to be built into clinical trials.

Adult↗
PubMed2000

Proviral HIV-1 DNA in gingival crevicular fluid of HIV-1-infected patients in various stages of HIV disease.

The oral cavity is rarely reported to be a site of human immunodeficiency virus (HIV) transmission, despite detectable virus in saliva and relatively frequent prevalence of periodontal disease in HIV-infected persons yielding increased excretion of mononuclear-cell-enriched gingival fluid. To search for possible sources of HIV in saliva, and using the polymerase chain-reaction technique, we sought the presence and shedding patterns of proviral HIV-1 DNA in gingival crevicular fluid in a group of patients previously determined as HIV-1-seropositive. Periodontal status at the collection sites was monitored by several clinical parameters, including Plaque Index, Gingival Index, probing depth, and clinical attachment loss. Gingival crevicular fluid samples were collected by means of paper points. Proviral HIV-1 DNA was detected in the gingival fluid of 17 out of 35 HIV-1-infected patients. Its detection correlated significantly with higher plasma HIV-1 RNA viral load (p = 0.03) and not with peripheral blood CD4+ cell count, the presence of blood in gingival fluid, or oral lesions. There was a significant correlation between clinical attachment loss at the sites of fluid collection and plasma HIV-1 RNA viral load (p = 0.002), and borderline correlation between the latter and probing depth (p = 0.54) in the group of patients harboring proviral HIV-1 DNA in gingival crevicular fluid. The results of our study suggest that mononuclear cells present in gingival crevicular fluid and harboring proviral HIV-1 DNA could represent a potential source of HIV-1 in the presence or absence of local bleeding, especially in persons with advanced HIV infection and increased loss of clinical attachment.

Adult↗
PubMed2003

Incorporating HIV prevention into the medical care of persons living with HIV. Recommendations of CDC, the Health Resources and Services Administration, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.

Reducing transmission of human immunodeficiency virus (HIV) in the United States requires new strategies, including emphasis on prevention of transmission by HIV-infected persons. Through ongoing attention to prevention, risky sexual and needle-sharing behaviors among persons with HIV infection can be reduced and transmission of HIV infection prevented. Medical care providers can substantially affect HIV transmission by screening their HIV-infected patients for risk behaviors; communicating prevention messages; discussing sexual and drug-use behavior; positively reinforcing changes to safer behavior; referring patients for services such as substance abuse treatment; facilitating partner notification, counseling, and testing; and identifying and treating other sexually transmitted diseases (STDs). To help incorporate HIV prevention into the medical care of HIV-infected persons, CDC, the Health Resources and Services Administration, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America developed these recommendations. The recommendations are general and apply to incorporating HIV prevention into the medical care of all HIV-infected adolescents and adults, regardless of age, sex, or race/ethnicity. They are intended for all persons who provide medical care to HIV-infected persons (e.g., physicians, nurse practitioners, nurses, physician assistants); they might also be useful to those who deliver prevention messages (e.g., case managers, social workers, health educators). The recommendations were developed by using an evidence-based approach. For each recommendation, the strength of the recommendation, the quality of available evidence supporting the recommendation, and the outcome for which the recommendation is rated are provided. The recommendations are categorized into three major components: screening for HIV transmission risk behaviors and STDs, providing brief behavioral risk-reduction interventions in the office setting and referring selected patients for additional prevention interventions and other related services, and facilitating notification and counseling of sex and needle-sharing partners of infected persons.

Adolescent↗
PubMed1995

Differential cytopathicity and susceptibility of Ghanaian highly divergent HIV-2 -GH2-, prototype HIV-2 -GH1-, and prototype HIV-1 -GH3- to inhibition by ddCyd and ddIno.

The cytopathicity and susceptibility of prototype HIV-1 [HTLVIIIB] and Ghanaian HIV isolates [GH1, GH2, GH3] to inhibition by ddCyd and ddIno were determined by the tetrazolium-based colorimetric method. HIV-1 [HTLVIIIB] caused the most cytopathic effect followed by HIV-2 [GH2]. At low MOI, HIV-2 [GH1] was more cytopathic than HIV-1 [GH3] but the reverse was true at high MOI. Using EC90 concentrations for comparison at similar cytopathicities, both HIV-1 [HTLVIIIB] and HIV-1 [GH3] which belong to prototype HIV-1 group, were effectively inhibited by one or both drugs. In contrast, HIV-2 [GH1] which belongs to prototype HIV-2 group, and especially, the highly divergent HIV-2 [GH2] which belongs to HIV-2b group were relatively resistant to inhibition by ddCyd and ddIno.

Antiviral Agents↗
PubMed2005

Comparative evaluation of the VIDAS HIV DUO Ultra assay for combined detection of HIV-1 antigen and antibodies to HIV.

The aim of the study was to evaluate the performance of the combined antigen and antibody HIV screening assay VIDAS HIV DUO Ultra (BioMérieux, Marcy l'Etoile, France) in comparison with two other combined tests: the former version of the same test (VIDAS HIV DUO, BioMérieux) and the AxSYM HIV Ag/Ab Combo assay (Abbott Laboratories, Rungis, France). A prospective study was performed on serum specimens received on a routine basis for HIV testing: 1443 blood samples were tested with the three assays. Sensitivity was 100% for the three tests. Specificity assessed on repeated false-positive samples was 99.86, 99.03 and 99.65% for VIDAS HIV DUO Ultra, VIDAS HIV DUO and AxSYM HIV Ag/Ab Combo, respectively. In addition, 14 seroconversion panels were tested with the VIDAS DUO Ultra and AxSYM HIV Ag/Ab Combo assays. For four of these panels, a positive signal was detected one blood sampling point earlier with the VIDAS DUO Ultra assay, corresponding to a higher sensitivity of the HIV antigen test. These results indicate that the VIDAS HIV DUO Ultra exhibits an improved specificity with comparison to the former version of this assay and an excellent sensitivity for early detection of HIV seroconversion.

AIDS Serodiagnosis↗
PubMed1999

Human immunodeficiency virus (HIV)-specific IgA and HIV neutralizing activity in the serum of exposed seronegative partners of HIV-seropositive persons.

The presence and activity of human immunodeficiency virus (HIV)-specific antibodies were analyzed in the sera of 15 sexually exposed seronegative persons who had systemic HIV-specific cell-mediated immunity and IgA-mediated mucosal immunity and in their HIV-infected partners. The HIV-positive subjects had HIV-specific serum IgG and IgA; the seronegative persons had HIV-specific serum IgA in the absence of IgG. Testing of the seronegative persons 1 year after the interruption of at-risk sex showed that no IgG seroconversion had occurred and that HIV-specific IgA serum concentrations had declined. Serum from the HIV-exposed seronegative persons was analyzed for the ability to neutralize primary HIV-1 isolates. Neutralizing activity was detected in 5 of 15 sera and in 2 cases was retained by serum-purified IgA. Thus, the immunologic picture for resistance to HIV infection should include HIV-specific cell-mediated immunity as well as HIV-specific IgA-mediated mucosal and systemic immunity.

Female↗
PubMed2006

HIV voluntary counseling and testing and HIV incidence in male injecting drug users in northern Thailand: evidence of an urgent need for HIV prevention.

HIV voluntary counseling and testing (VCT), an important strategy for HIV prevention and care, has been available in all government hospitals in Thailand since 1992. We assessed factors associated with HIV testing, its uptake, and estimates of HIV incidence after HIV testing among male northern Thai injecting drug users (IDUs) admitted for inpatient drug treatment. Participants were interviewed about risk behaviors and HIV testing history before VCT was provided as part of the study. Of 825 IDUs who participated, 36% reported a prior HIV test. Factors associated with prior HIV testing in multiple logistic regression analysis included higher education and having >1 lifetime sex partner. Needle sharing was not associated with prior HIV testing. Of the 298 men with a prior test, 80% reported a negative result on their last prior HIV test, of whom 28% tested positive in our study, leading to an estimated incidence rate of 10.2 per 100 person-years. Fifty-nine percent of the IDUs who reported a prior HIV test stated that they did not receive pre- and/or posttest counseling. HIV incidence among IDUs remains high despite having VCT. Extending HIV prevention and harm reduction programs is urgently needed for IDUs in the region.

AIDS Serodiagnosis↗
PubMed2005

Targeted infection of HIV-1 Env expressing cells by HIV(CD4/CXCR4) vectors reveals a potential new rationale for HIV-1 mediated down-modulation of CD4.

BACKGROUND: Efficient targeted gene transfer and cell type specific transgene expression are important for the safe and effective expression of transgenes in vivo. Enveloped viral vectors allow insertion of exogenous membrane proteins into their envelopes, which could potentially aid in the targeted transduction of specific cell types. Our goal was to specifically target cells that express the T cell tropic HIV-1 envelope protein (Env) using the highly specific interaction of Env with its cellular receptor (CD4) inserted into the envelope of an HIV-1-based viral vector. RESULTS: To generate HIV-1-based vectors carrying the CD4 molecule in their envelope, the CD4 ectodomain was fused to diverse membrane anchors and inserted together with the HIV-1 coreceptor CXCR4 into the envelopes of HIV-1 vector particles. Independent of the type of CD4 anchor, all chimeric CD4 proteins inserted into HIV-1 vector envelopes and the resultant HIV(CD4/CXCR4) particles were able to selectively confer neomycin resistance to cells expressing the fusogenic T cell tropic HIV-1 Env protein. Unexpectedly, in the absence of Env on the target cells, all vector particles carrying the CD4 ectodomain anchored in their envelope adhered to various cell types without infecting these cells. This cell adhesion was very avid. It was independent of the presence of Env on the target cell, the type of CD4 anchor or the presence of CXCR4 on the particle. In mixed cell populations with defined ratios of Env+/Env- cells, the targeted transduction of Env+ cells by HIV(CD4/CXCR4) particles was diminished in proportion to the number of Env- cells. CONCLUSION: Vector diversion caused by a strong, non-selective cell binding of CD4+-vector particles effectively prevents the targeted transduction of HIV-1 Env expressing cells in mixed cell populations. This Env-independent cell adhesion severely limits the effective use of targeted HIV(CD4/CXCR4) vectors designed to interfere with HIV-1 replication in vivo. Importantly, the existence of this newly described and remarkably strong CD4-dependent cell adhesion suggests that the multiple viral efforts to reduce CD4 cell surface expression may, in part, be to prevent cell adhesion to non-target cells and thereby to increase the infectivity of viral progeny. Preventing CD4 down-modulation by HIV-1 might be an effective component of a multi-faceted antiviral strategy.

Animals↗
PubMed1993

Quantitative analysis of the human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: differential CTL responses to HIV-1 and Epstein-Barr virus in late disease.

Major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) are part of the cellular immune response to human persistent virus infections. Measurements of the frequency and specificity of human immunodeficiency virus type 1 (HIV-1)-specific CTL and their variation with time may indicate their relative importance in modulating the progression of HIV-1 infection. We have used limiting dilution analysis (LDA) to derive quantitative estimates of the frequency of HIV-1-specific CTL precursors in a cross-sectional study of 23 patients at different clinical stages of HIV-1 infection and to compare these with the frequency of CTL precursors specific for another persistent virus (Epstein-Barr virus [EBV]) in the same patients. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with autologous HIV-1-infected lymphoblasts and assayed for cytotoxicity in 51Cr release assays against autologous and MHC-mismatched lymphoblastoid B cells infected with recombinant vaccinia viruses expressing the three HIV-1 structural gene products. The frequency of MHC-restricted precursors was high in asymptomatic HIV-1-infected patients (env-specific CTL precursors up to 73/10(6) PBMC; gag-specific CTL precursors up to 488/10(6) PBMC), although the relative frequency against the different structural gene products varied from patient to patient. The HIV-1-specific CTL precursor frequency was reduced in patients who had more severe (< 400/microliters) CD4+ lymphocyte depletion, while in the majority of such patients the frequency of CTL precursors against EBV was maintained at levels observed in healthy controls. Direct CTL activity in unstimulated PBMC was observed in three of nine patients but no correlation was found between the presence of an activated CTL response and the magnitude of the CTL response detected after stimulation in LDA. Thus, CTL precursors were detected against all three HIV-1 structural gene products in patients with CD4+ lymphocyte counts > 400/microliters, at frequencies that are high compared with those reported for other persistent viruses. A CTL response directed against multiple protein antigens of HIV-1 may protect the patient against epitope variation. The fact that the EBV-specific CTL precursor frequencies were maintained in advanced HIV-1 infection suggests that there may be selective impairment of the HIV-1-specific CTL response associated with disease progression.

Adult↗
PubMed2002

HIV-1 gp120 proteins and gp160 peptides are toxic to brain endothelial cells and neurons: possible pathway for HIV entry into the brain and HIV-associated dementia.

Breakdown of the blood-brain barrier is commonly seen in patients with human immunodeficiency virus (HIV)-associated dementia, despite the lack of productive HIV-infection of the brain endothelium. Through this damaged blood-brain barrier, HIV and HIV-infected monocytes/macrophages infiltrate the brain and further infect microglia and brain macrophages. Neuronal cell death and dysfunction are the underlying cause of HIV-associated dementia, but no productive HIV-infection of neurons has been documented. It is likely that secreted viral products play a major role in blood-brain barrier damage and neuronal cell death. The aim of the present study was to examine the effect of HIV-1 gp160 peptides and gp120 proteins on brain microvascular endothelial cells and neurons from both human and rats. Four of the 7 gp160 peptides tested evoked significant neurotoxicity. Two different full-length recombinant HIV gp120 proteins (HIV-1CM235 gp120 and HIV-1MN gp120) also induced neuronal and brain endothelial cell death, and concentrations as little as 1 ng/ml evoked pronounced morphological changes in these cells and marked cytotoxicity. This study suggests that HIV proteins and peptides that are shed in vivo may be directly involved in blood-brain barrier damage and neuronal cell death in HIV-associated dementia.

AIDS Dementia Complex↗
PubMed1999

Cell-associated HIV-1 messenger RNA and DNA in T-helper cell and monocytes in asymptomatic HIV-1-infected subjects on HAART plus an inactivated HIV-1 immunogen.

OBJECTIVE: We examined the effect of an HIV-1-specific immune-based therapy on cell-associated HIV-1 DNA and RNA. DESIGN: Five HIV-1-infected subjects receiving HIV-1 immunogen plus HAART were compared with three HIV-1-infected subjects who received incomplete Freund's adjuvant (IFA) plus HAART. METHODS: Cell-associated HIV-1 RNA or DNA in lymphocytes and monocytes was determined using a dual immunophenotyping/in situ hybridization assay with or without in situ PCR amplification. RESULTS: Cell-associated HIV-1 RNA in CD4 cells correlated with plasma RNA overall. CD4, HIV-1 gag-pol messenger (m)RNA+ cells decreased in the immunogen plus HAART group compared with the IFA plus HAART group. Decreases in HIV-1 DNA+ CD4 cells were observed in the immunogen plus HAART compared with the IFA plus HAART group. Decreases in HIV-1 gag-pol mRNA+ monocytes were observed in the immunogen plus HAART group compared with the IFA plus HAART group. Consistent with the findings in CD4 cells, decreases in HIV-1 DNA+ monocytes were observed in the immunogen plus HAART group compared with the IFA plus HAART group. CONCLUSIONS: These preliminary observations support the rationale for examining the combination of immune-based therapies and antiretroviral drugs for effective HIV-1 control.

AIDS Vaccines↗