Sequential serological studies of homosexual men with and without HIV infection. Epstein-Barr virus activation preceding and following HIV seroconversion.

Viral cofactors may be important in the pathogenesis of HIV infection and the development of AIDS, but their role is still imperfectly understood. Sequential serological studies were performed in a cohort of 100 homosexual men and 70 matched healthy controls over a mean period of 4 years. Of the patients, 18 were found to be HIV+ on admission to the study and 15 seroconverted to HIV+ during the follow up (seroconversion group). Serum antibodies of both IgG and IgA isotypes against Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were determined. IgG antibodies indicate past infection, while a marked increase in IgG titre or a positive IgA titre were taken to indicate active infection or reactivated latent infection. EBV and CMV infections were about two to four times more prevalent in the homosexual men both HIV- and HIV+, compared with controls. Active infections were increased in the homosexual men and particularly in the HIV+ patients. The seroconversion group revealed activation of both EBV and CMV following HIV infection. When the antibody profile of seroconverting patients at the time preceding seroconversion was compared with a matched group of 39 homosexual men who remained HIV-, no change was found in CMV antibodies, but four out of 15 (26.6%) of the patients had high titres of anti-EBV IgA preceding seroconversion, as compared with only one out of 39 (2.6%) of HIV- homosexual men (P less than 0.05). This suggests a role for EBV reactivation in the pathogenesis of HIV infection in some patients.     

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.     

Surrogate markers for disease progression in treated HIV infection.

OBJECTIVE: To characterize the relationships among highly active antiretroviral therapy (HAART), HIV-1 RNA levels, immune system markers, and clinical outcome in a cohort of HIV-1-infected homosexual men. PATIENTS: A total of 123 men enrolled in the Amsterdam cohort study of HIV-1 infection and AIDS with a documented seroconversion for HIV-1 antibodies and known date of seroconversion were included in this study. METHODS: CD4 + /CD8 + T-cell counts and HIV-1 RNA levels in plasma were measured approximately every 6 months. Dates of starting and stopping antiretroviral therapy were also recorded. The relationship between HIV-1 RNA in plasma, CD4 + /CD8 + T-cell counts and HAART and their influence on clinical outcome were examined using a graphical chain modeling approach. Generalized estimating equations were used to examine correlations among the three disease markers. Hazards models with time-dependent covariates were used to examine the influence of HAART and the disease markers on progression to AIDS. RESULTS: HAART was significantly associated with reduced disease progression (relative hazard [RH] of AIDS, 0.20;, 95% confidence interval [CI], 0.05-0.85). The most recent HIV-1 RNA measurement and CD4 + T-cell count are independently associated with disease progression (adjusted RH for HIV-1 RNA 1.8 per log 10 increase; 95% CI, 1.2-2.6, p =.002; adjusted RH for CD4 + 0.48 per 100 x 10(6)/L increase; 95% CI, 0.40-0.58; p <.001). Depending on these measurements, HAART was no longer significantly associated with AIDS (adjusted RH, 0.81; 95% CI, 0.18-3.6; p =.78). CONCLUSIONS: HIV-1 RNA levels in plasma and CD4 + T-cell counts are currently considered as effective surrogate markers for the effect of HAART on disease progression in this cohort.     

Low T-cell responsiveness to activation via CD3/TCR is a prognostic marker for acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus-1 (HIV-1)-infected men

In a cohort of 300 HIV-1-infected homosexual men, studied longitudinally, the prognostic value of T-cell proliferative responses for development of AIDS was analyzed. In 15 persons we observed that, at seroconversion, T-cell reactivity to anti-CD3 monoclonal antibody (Mab) and phytohemagglutinin (PHA) was decreased to 20 and 60% of the normal values, respectively. After seroconversion, within 3 months, the response to anti-CD3 Mab and PHA returned to 60 and 80%, respectively, of the normal magnitude and declined thereafter. To investigate whether low T-cell reactivity correlated with progression to AIDS, groups of progressors and nonprogressors were compared. In individuals who progressed to AIDS, already 12 months before diagnosis, responses to anti-CD3 Mab were virtually absent, whereas at that time CD4+ cell numbers and reactivity to horse anti-human lymphocyte serum and PHA were still comparable to values observed for nonprogressors and the asymptomatic population as a whole. In a disease-free survival analysis, low anti-CD3 Mab reactivity predicted progression to AIDS. Our findings demonstrate that low T-cell responsiveness to anti-CD3 Mab is an early marker of progression toward AIDS in HIV-1 infected individuals.     

Coincidental appearance of LAV/HTLV-III antibodies in hemophiliacs and the onset of the AIDS epidemic

To determine when antibody to lymphadenopathy-associated virus (LAV) emerged in the US hemophiliac population, serum bank samples that had been collected from hemophiliacs from California, Georgia, New York, and Texas in 1968 and in 1978-84 were tested for antibody to viral proteins p25 and p41 of LAV. Antibody to LAV was not detected in the serum samples collected in 1968-69 from 15 patients with mild hemophilia A. Before 1980, it was present in only 1 of 21 California patients with hemophilia A. Among the latter group, seroconversion tended not to occur until 1982, rapidly increased in 1983, and had reached a rate of over 85% by 1984. Among Georgian hemophiliacs, 8 of 14 (57%) were seropositive in 1981 and 8 of 8 (100%) were positive in 1984. The extent of seroconversion was not as great among patients with hemophilia B as among those with hemophilia A. None of the patients with antibody to LAV has contracted acquired immunodeficiency syndrome (AIDS). Of the 22 patients who received factor VIII concentrates (21 with hemophilia A and 1 with von Willebrand's disease), 7(32%) have mild lymphadenopathy. Of the 7 patients who received factor IX concentrates (6 with hemophilia B and 1 with a factor VII deficiency), only 1 had lymphadenopathy. These findings show that LAV exposure is widespread among patients receiving factor VIII concentrate and suggest that the concentrate may have contained LAV during 1980-83. Of interest was the observation that seroconversion in hemophiliacs began shortly after the outbreak of the AIDS epidemic among homosexual men and intravenous drug users (1979-80), and the timing of seroconversion correlates with the 1st cases of AIDS in hemophiliacs in late 1981-early 1982. The temporal relationship between seroconversion and the epidemic among hemophiliacs supports the hypothesis that LAV is the etiologic agent of AIDS.     

Prospective multicenter study on isolation of human immunodeficiency virus type 1 from homosexual men after seroconversion.

A prospective multicenter study was undertaken to isolate human immunodeficiency virus type 1 (HIV-1) from 45 homosexual men for a period of 30 months after seroconversion. Efficiency of HIV-1 isolation from peripheral blood mononuclear cells was relatively stable over time, ranging from 64% at the time of seroconversion to more than 82% after 18 months of seroconversion. However, Kaplan-Meier analysis of HIV-1 culture data indicates that the cumulative proportion of HIV-1 culture positivity at 3, 6, 12, and 18 months after seroconversion was 62, 65, 84, and 92%, respectively. No significant correlation was observed between the presence of HIV-1 p24 antigen in serum, or numbers of CD4+ and CD8+ blood lymphocytes, and HIV-1 isolation within this period of time. These data suggest that HIV-1 viremia in homosexual men gradually increases to almost 100% culture positivity by 18 months after seroconversion.     

Characterization of high-risk HIV-1 seronegative hemophiliacs

Mechanisms that protect most high-risk HIV-1 seronegative (HRSN) persons are not well understood. Among hemophiliacs from the Multicenter Hemophilia Cohort Study who remained HIV-1 seronegative despite a high (94%) risk for acquisition of HIV-1 infection, only 7/43 were homozygous for the protective CCR5 Delta32 polymorphism. Among the remainder, neither CCR5 density nor beta-chemokine production, nor in vitro susceptibility to infection with the HIV-1 isolate JR-FL could distinguish HRSN hemophiliacs from healthy controls. When compared to lymphocytes of healthy controls not at risk for HIV-1 infection, diminished spontaneous lymphocyte proliferation was seen in lymphocytes of HRSN hemophiliacs as well as in lymphocytes of hemophiliacs not at risk for HIV-1 infection. Surprisingly sera/plasmas obtained from high-risk HIV-1 seropositve hemophiliacs prior to seroconversion more often contained alloreactive antibodies than date-matched sera/plasmas obtained from HRSN hemophiliacs. Thus alloreactivity may predispose to acquisition of HIV-1 infection after parenteral exposure.     

Failure to confirm HIV infection in two end-stage HIV/AIDS patients using a popular commercial line immunoassay

Immunoassays using either viral lysate (Western blot) or recombinant/synthetic antigen (immunoblot) for anti-HIV capture are still the preferred method to confirm HIV infection. Two cases of HIV-1-infected patients presented with acquired immunodeficiency syndrome (AIDS)-defining illnesses. Laboratory tests were performed using multiple commercial HIV test kits on multiple sera from both patients over several weeks. Both patients were strongly positive on the anti-HIV/p24 antigen combined screening assay. Yet, HIV-1 infection could not be confirmed using a popular commercial immunoassay. Eventually, HIV infection was confirmed using an alternative commercial Western blot assay as well as an HIV quantitative PCR test. In laboratories without nucleic acid testing (NAT) for HIV, indeterminate results may delay confirmation of HIV infection, if commercial line immunoassays alone are available. Some end-stage HIV/AIDS patients may not produce antibodies to specific HIV antigens and may therefore give indeterminant or negative results on some immunoassays, depending on the type of antigen used. This report highlights the utility of having NAT available when diagnosing difficult cases of HIV infection, especially in light of the recent Centers for Disease Control and Prevention move towards more universal, routine, HIV testing.     

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.     

Development of antibodies to HIV-1 is associated with an increase in circulating CD3+CD4-CD8- lymphocytes

This study investigated whether seroconversion with respect to human immunodeficiency virus, type 1 (HIV-1) was associated with an increase in lymphocytes expressing the CD3+CD4-CD8- phenotype. Proportions and absolute numbers of CD3+, CD4+, and CD8+ lymphocytes were determined prospectively over a 2.5-year period on 4954 homosexual and/or bisexual men participating in the Multicenter AIDS Cohort Study. Of the 4808 men whose serostatus at entry could be verified, 1745 were seropositive (SP) for antibodies to HIV-1 at entry into study, 2795 were uniformly seronegative (SN) for HIV-1 for 30 months, and 268 were seroconverters (SC) with respect to HIV-1 during this period. For each of six semiannual evaluations, proportions and numbers of CD3+CD4-CD8- lymphocytes (calculated as CD3- (CD4 + CD8] were both significantly greater in the SP group than in the SN group (P less than 0.001). Mean CD3+CD4-CD8- levels in the SC group were indistinguishable from those in the SN group before seroconversion, but by 3-9 months after seroconversion the SC group demonstrated absolute numbers of CD3+CD4-CD8- lymphocytes which were significantly increased (P less than 0.001) compared to the SN group using linear regression methods with adjustment for correlation of measurements within an individual over time. An additional significant increase occurred by 21-27 months after seroconversion (P = 0.006). These results are consistent with an association of HIV-1 seroconversion with an increase in circulating T lymphocytes expressing the CD3+CD4-CD8- phenotype (double negative T cells), a decrease in CD3-CD4-CD8+ natural killer cells, or both. An increase in double negative T cells could reflect a host defense mechanism against HIV-1 or effects of HIV-1 on T cell development.     

Detection of human immunodeficiency virus (HIV) type 1 antibodies by new automated microparticle enzyme immunoassay for HIV types 1 and 2.

We compared an automated microparticle double-antigen sandwich enzyme immunoassay (EIA) for the IMx test system recently developed by Abbott with two established assays (the automated indirect Vidas IgG EIA and the double-antigen sandwich EIA from Murex/Wellcome) devised for the detection of human immunodeficiency virus type 1 (HIV-1) and HIV-2 antibodies. A total of 1,078 consecutive serum samples were tested prospectively with the three assays. In addition, we used retrospectively selected panels of serum samples with discrepant results in two different screening tests and with indeterminate or positive Western immunoblot (WB) results, as well as five commercially available HIV-1 seroconversion panels. The new assay showed excellent discriminatory characteristics for the separation of samples from HIV-1-positive and HIV-1-negative persons according to Centers for Disease Control and Prevention WB criteria. The sensitivities were 98.1, 92.9, and 96.1% for the new test and the two other assays, respectively, and the specificities were 99.7, 97.9, and 98.1%, respectively. With the seroconversion panels this new test was positive several days earlier than the two other assays; i.e., seroconversion was evident at the peak of p24 antigenemia and often several weeks before WB became positive by the most stringent criteria.     

Speed of progression to AIDS and degree of antibody response to accessory gene products of HIV-1

Antibodies to E. coli-produced HIV-1 nef, rev, tat, vpu, and vpr proteins were measured by enzyme immunoassay in serial sets of sera from 72 men seroconverting for antibodies to HIV-1 structural proteins, and from 190 initially symptom-free men who were seropositive for these antibodies at entry into the study. In the men seroconverting for antibodies to structural proteins the levels of nef-, rev-, and tat-specific antibodies, but not of vpu-, and vpr-specific antibodies, within 3 months of seroconversion, appeared to be lower in the five men progressing to AIDS, compared with the men remaining symptom-free during follow-up. Analysis of the prevalence of previously described antibody profiles to these accessory gene products was carried out. In all HIV-1 antibody seroconverters and in those HIV-1 antibody seropositive men with 15 or more months of follow-up who progressed to AIDS, there was a shift from predominantly nef- and vpu-specific antibody negative profiles in the men developing AIDS in the early years of the study to predominantly nef- and vpu-specific antibody positive profiles in men who developed AIDS later. Rev- and tat-specific antibody negative profiles were dominant in men progressing to AIDS throughout follow-up. No vpr-specific antibody profile occurred preferentially in the men progressing to AIDS throughout follow-up. Low antibody reactivity to accessory gene products nef, rev, and tat appears, like low anti-core antibody reactivity, to be associated with progression to AIDS relatively rapidly after infection with HIV-1.     

HIV-1 IgA specific serum antibodies and disease progression during HIV-1 infection

OBJECTIVE: To evaluate the role of serum human immunodeficiency virus type 1 immunoglobulin A (HIV-1 IgA) antibodies in the progression of HIV-1 infection in relation to viral load and CD4 cell counts. METHODS: Sequential serum specimens were obtained from 218 homosexual men: 123 HIV-1 seropositives, 24 HIV-1 seroconverters, and 71 HIV-1 seronegatives. HIV-1 IgA antibodies were tested blindly by enzyme-linked immunosorbent assay and Western blot. T-lymphocyte subsets were measured by flow cytometry. Viral plasma load was determined by a sensitive branched DNA assay. RESULTS: HIV-1 IgA antibodies with a titer greater than or equal to 50 were detected among 50% of the seroconverters, 27% of the HIV-1-seropositive asymptomatic subjects, 25% of lymphadenopathy, and 23% of HIV-1-related symptomatic subjects. Among patients with the acquired immune deficiency syndrome, the prevalence of virus-specific IgA antibodies (55%) was significantly higher (p < 0.03) as compared with the HIV-1-seropositive asymptomatic subjects, lymphadenopathy and HIV-1-related symptomatic patients, but not versus the seroconverters (p = 0.8). IgA antibodies to HIV-1 gP160 were the most prevalent among all subjects tested. A significant decrease in CD4 cell counts was observed after HIV-1 seroconversion. Viral load was slightly higher among the seroconverters who demonstrated higher (> or =50) HIV-1 IgA levels. CONCLUSIONS: HIV-1 IgA serum antibodies did not predict the progression of the disease. Correlation between HIV-1 IgA antibodies titer, viral load, and CD4 cell counts was not detected.     

Prevalence of antibodies to herpes simplex virus 2 among homosexual men either positive or negative for human immunodeficiency viruses in Slovakia

We determined the prevalence of antibodies to herpes simplex virus 2 (HSV-2, HSV-2 antibodies) in sera of homosexual men either positive for human immunodeficiency virus 1 (HIV-1, HIV+, a group of 27 sera) or negative for HIV-1 and HIV-2 (HIV-, a group of 52 sera) in Slovakia. Antibodies to HSV-2 glycoprotein G-2 (gG-2, gG-2 antibodies) were determined by a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) and immunoblot analysis. We found that 40% of HIV+ and 23% of HIV- homosexual men were positive for the gG-2 antibodies, what is 3.6 and 2.1 times higher incidence, respectively, than that in the control heterosexual population (Bystrická et al., Acta Virol. 42, 319-324, 1998). Identification of individuals infected with genital herpes among HIV+ and HIV- homosexual men should be succeeded by antiviral therapy in order to prevent transmission of HSV-2 and HIV as well in this community.     

Natural antibodies to HIV-tat epitopes and expression of HIV-1 genes in vivo

The tat regulatory protein of HIV-1 was expressed as a fusion protein in E. coli and used as antigen to detect antibodies against HIV-tat (anti-tat) in the serum of HIV-1 infected children and adults. HIV-1-infected children showed a higher frequency (55%) of anti-tat than HIV-1-infected adults (36%). Anti-tat were present in only 15% (3/20) of acutely infected individuals. Forty percent (10/25) of individuals with prolonged HIV-1 infection but without antigen were anti-tat positive. Only 13% (3/23) of HIV-1-antibody-positive individuals with prolonged HIV-1 antigenemia were anti-tat positive and titers of anti-tat antibodies declined with time. Pepscan analysis identified the amino terminus of HIV-tat as the major antibody-binding site. Antibodies to HIV-tat occurred as a harbinger of HIV-1 antigen expression and disappeared thereafter, possibly reflecting the transience of HIV-tat expression. Because of the low antigenicity of HIV-tat, antibodies to this regulatory protein are not a reliable marker for either early HIV-1 infection or subsequent disease progression.     

Antibody to human endogenous retrovirus peptide in urine of human immunodeficiency virus type 1-positive patients.

Human endogenous retrovirus (HERV)-like sequences are normal inherited elements that constitute several hundredths of the human genome. The expression of genes located within these elements can occur as a consequence of several different events, including persistent inflammation or genotoxic events. Antibodies to endogenous retroviral gene products have been found in a number of infectious, chronic, and malignant diseases, suggesting a role in disease initiation and progression. We studied human immunodeficiency virus type 1 (HIV-1)-infected patients for evidence of urine antibody to a HERV peptide and investigated correlates with clinical and laboratory parameters. Forty-three HIV-1-infected patients in documented asymptomatic, symptomatic, or AIDS stages of disease and 21 age- and gender-matched, uninfected controls were tested for antibody to HERV-related peptide 4.1. Urine specimens were examined in a blinded fashion with the Calypte Biomedical Corp. experimental enzyme immunoassay for antibody to peptide 4.1. Results were compared with demographic data, medical history, clinical state of disease, and results of other laboratory tests. Thirty-six percent of the asymptomatic (Centers for Disease Control and Prevention [CDC] category A) and 81.3% of both the symptomatic (CDC category B) and AIDS (CDC category C) patients were positive for antibody to HERV-related peptide 4.1. None of the controls were positive. In this study, antibodies to HERV-related peptide 4.1 were found more frequently in patients with advanced stages (categories B and C) of HIV-1 disease than in those patients with an earlier stage (category A) of HIV disease. In HIV patients, severe immunosuppression, defined as having had at least one opportunistic infection, correlated with the expression of antibody to a HERV-related peptide.     

Increases in soluble CD8 antigen in plasma, and CD8+ and CD8+CD38+ cells in human immunodeficiency virus type-1 infection.

Increases in plasma levels of soluble CD8 (SCD8) antigen and expansion of the CD8+ CD38+ lymphocyte compartment were early immunologic alterations frequently observed prior to detection of antibodies against human immunodeficiency virus type 1 (HIV-1) and diminution of CD4+ cells in subjects at risk to develop AIDS. These increases identified in the 49 seronegative homosexual men were manifest in all 164 homosexual subjects and 45 intravenous drug users (IVDU) positive for HIV-1 antibodies (HIV-1+), 19 patients with ARC, and 29 AIDS patients. Augmentation of plasma sCD8 antigen correlated with increases in both CD8+ and CD8+ CD38+ cells in HIV-1(-) homosexual men (r = 0.35, P less than 0.013; r = 0.48, P less than 0.0005; respectively) and the 258 HIV-1+ subjects (r = 0.25, P less than 0.0003; r = 0.33, P less than 0.0001, respectively). In vitro examination of unstimulated peripheral blood lymphocytes from HIV-1+ homosexuals and IVDU confirmed the fivefold higher constitutive levels of cellular release of sCD8 antigen in these subjects compared to heterosexual controls. Inclusion of radiolabeled amino acids during the 3-day culture period in the presence or absence of phytohemagglutinin resulted in negligible levels of radioactivity associated with the sCD8 antigen indicative of a lack of de novo synthesis. Throughout clinical progression to AIDS, sCD8 antigen levels continued to escalate relative to the numbers of CD8+ cells bearing CD38+ antigen. The data confirm the interrelationship between sCD8+ antigen and CD8+ and CD8+ CD38+ cells.     

Functional antibody response to human cytomegalovirus in immunocompetent and HIV-1 infected individuals with antibodies that inhibit virus penetration into cells and intercellular transmission of viral infection.

Antibodies mediating post-attachment virus neutralisation (PN), inhibition of human cytomegalovirus (HCMV)-induced cell fusion in the glioblastoma cell line U373 (IF) and global neutralising activity (NA) were quantified in sera from healthy immunocompetent individuals, asymptomatic HIV-1-infected subjects and AIDS patients to further characterise the neutralising antibody response to HCMV in these population groups and to assess whether HIV-1-infected individuals exhibited an abnormal functional antibody profile. PN and IF antibodies accounted for a minor fraction of the NA activity of sera from all population groups. Sera from HIV-1-infected individuals (particularly AIDS patients) displayed higher levels of PN and IF antibodies than those from the healthy control group; however, the relative contribution of these antibodies to the global serum NA activity appeared to be lower in the former individuals than in immunocompetent controls. Serum antibodies preventing HCMV cell-to-cell spread (IP) were then measured to determine whether a specific deficiency could be detected in the HIV-1-infected group population. Serum IP antibody titres were significantly higher in HIV-1-infected individuals (particularly in AIDS patients) than in controls. The potential implications of the data for explaining the pathogenesis of HCMV infection are discussed.     

Immune complexes in the acquired immunodeficiency syndrome (AIDS): Relationship to disease manifestation,risk group,and immunologic defect

Immune complex assays (and other immunologic tests) were performed on sera from 162 patients with the acquired immunodeficiency syndrome (AIDS) and 275 AIDS-related subjects. Immune complexes were detected in 89% of AIDS patients and 93% of homosexual men with lymphadenopathy. Immune complex levels in AIDS patients were not associated with a particular risk group or with types of opportunistic infection or malignancy; however, they correlated with other laboratory features of the immune defect (depression in T helper cells and T helper/suppressor-cell ratio, and IgG levels). Immune complexes were also detected in a lesser proportion of risk-group controls (homosexual men, hemophiliacs, Haitians). In risk-group controls, immune complex levels were associated with certain features reflecting sexual practice, blood product exposure, or infection, but these features did not account for the higher levels found in AIDS patients. In appropriate situations, immune complex assays may be of value as screening tests or, possibly, as prognostic indicators for AIDS or AIDS-related syndromes.