Human Immunodeficiency Virus Antigenemia Research Articles

Immunological and viral markers of HIV infection and retinal microangiopathy.

The relationship between retinal microangiopathy and some features of human immunodeficiency virus (HIV) infection such as HIV antigenemia, antibodies to the viral proteins, T lymphocyte subsets, were studied in 71 patients with acquired immunodeficiency syndrome (AIDS). The absence of antibodies to the HIV p24 protein was significantly related to retinal microangiopathy (p = 0.0051) and more closely to retinal cotton-wool spots (p = 0.0007); the combination of positive antigenemia with the absence of antibodies to p24, which is typical of the later phases of HIV infection, was found in a larger percentage of patients with cotton-wool spots (p = 0.0013) than in subjects with every sign of microangiopathy (p = 0.0546). T-helper (CD4+) cells count below 200 cells/mm3 was also detected in a higher percentage of patients with HIV-related retinal microangiopathy (p = 0.009). These findings suggest that retinal microangiopathy and especially retinal cotton-wool spots are related to the progression of immunodeficiency.

Incidence of zidovudine-resistant human immunodeficiency virus isolated from patients before, during, and after therapy.

The zidovudine sensitivity of 372 isolates of human immunodeficiency virus (HIV) obtained from 237 patients before, during, and after treatment with zidovudine was examined. Virus resistant to > 0.5 micrograms/mL (1.87 microM) zidovudine was isolated from most patients (93%) after 36 months of therapy. Zidovudine-sensitive virus was isolated from 5 of 15 patients who had ended antiretroviral therapy but had previously shed resistant virus. The emergence of sensitive virus after end of therapy appeared to be influenced by both the duration of treatment and the time off drug. Patients with resistant virus tended to have low CD4 cell counts and HIV antigenemia at the commencement of therapy, suggesting that these two factors are important in the development of drug resistance.

Eight Year Prospective Study of HIV Infection in a Cohort of Homosexual Men—Clinical Progression, Immunological and Virological Markers

Three hundred and fourteen homosexual/bisexual men at risk for human immunodeficiency virus (HIV) infection (170 seroprevalent HIV-positive, 144 seronegative) were prospectively studied over 8 years to assess rates of HIV infection and disease progression, in conjunction with cellular and HIV serological markers. In HIV-positive subjects, CD4+ lymphocyte counts rose strikingly during the period surrounding seroconversion, then fell progressively over the intervening period to a mean level of 300 cells/mm3 when AIDS developed. Changes in CD8+ lymphocyte counts were less consistent. The trend for HIV serological markers over the study period was of progressive decline in the proportion of subjects with anti-p24 antibody, associated with an increase in the proportion of subjects with detectable HIV antigenaemia. However, only 45% of subjects tested had lost anti-p24 antibody by the time of AIDS diagnosis, and HIV antigen was detectable up to 4 years before this. Different HIV serological patterns were also observed in subjects presenting either with Kaposi's sarcoma or opportunist infections. Our data support the continued use of cellular and virological markers in the evaluation of HIV disease; however, the variability observed in this study highlights their limited ability in predicting specific clinical events. Care should therefore be taken to encompass both clinical and laboratory information in the medical assessment of the HIV-infected individual.

Human immunodeficiency virus (HIV)-infected tumor xenografts as an in vivo model for antiviral therapy: role of alpha/beta interferon in restriction of tumor growth in nude mice injected with HIV-infected U937 tumor cells

The host factors involved in the restriction of tumor growth were studied in nude mice transplanted with a cloned line of chronically human immunodeficiency virus (HIV)-infected U937 cells. HIV-infected and uninfected U937 cells exhibited the same growth patterns in culture. However, HIV-infected cells were not tumorigenic when injected subcutaneously in nude mice, whereas large solid tumors were observed in mice injected with uninfected U937 cells. Injection of nude mice with antibody to alpha/beta interferon (IFN-alpha/beta) enabled HIV-infected U937 cells to grow progressively in approximately 90 to 100% of mice. HIV-infected U937 cells formed solid tumors in the majority (60 to 90%) of either immunosuppressed (splenectomized, irradiated, and anti-asialo-GM1-treated) or genetically immunodeficient (bg/nu/xid) nude mice. In mice treated with antibodies to IFN-alpha/beta with established HIV-positive tumors, a direct correlation was found between p24 antigenemia and tumor size. Treatment of established HIV-positive U937 cell tumors with human IFN-alpha or mouse IFN-alpha/beta resulted in a clear-cut inhibition of both tumor growth and p24 HIV antigenemia. In contrast, treatment with tumor necrosis factor alpha markedly inhibited tumor growth but did not significantly decrease serum p24 levels. 3'-Azido-3'-deoxythymidine treatment did not affect either tumor growth or the levels of serum p24 antigen. These data indicate that endogenous IFN-alpha/beta is a crucial factor in the restriction of both tumor growth and p24 antigenemia in mice injected with HIV-infected tumor cells. Moreover, the results suggest that the development of HIV-1 p24 antigenemia in athymic immunosuppressed mice may represent an interesting in vivo model for anti-HIV therapy.

RISK FACTORS FOR PROGRESSION OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION AMONG SEROCONVERTED AND SEROPOSITIVE HOMOSEXUAL MEN

For identification of risk factors for progression of human immunodeficiency virus (HIV) infection, 746 homosexual men participating in a cohort study in Amsterdam, The Netherlands, were studied since October 1984. A total of 234 of these men were HIV antibody-positive at baseline, and 52 seroconverted during follow-up. These 286 individuals were categorized as high- and low-risk for progression to the acquired immunodeficiency syndrome (AIDS) on the basis of the presence or absence of HIV antigenemia, antibody to HIV core antigen, or a number of T helper lymphocytes less than 0.5 x 10(9)/liter during three or more subsequential blood samples. Ninety-six (41%) of the seropositives and 32 (62%) of those who seroconverted remained low-risk throughout the study period. Bivariate analyses revealed that educational level and a history of herpes zoster were associated with a low- and high-risk status, respectively. In multivariate analyses, a history of herpes zoster and a history of sexual intercourse with a person who had AIDS were associated with a more rapid disease progression. While herpes zoster is considered to be a marker of progressive immunodeficiency, a history of having sexual intercourse with a person who had AIDS points to the more virulent properties of HIV in these persons. Because both seropositives and seroconverters who had sexual intercourse with a person with AIDS had a more rapid disease progression, it seems plausible that being infected by a person with AIDS is a risk factor for a relative short incubation period.

Markers of HIV Infection Prior to IgG Antibody Seropositivity

During a 1-year period of study at two plasma collection centers, 7 of 35,000 plasma donors seroconverted to the human immunodeficiency virus (HIV) and had stored plasma samples that predated or antedated the seroconversion period. From each donor, three to eight plasma samples that had been collected at 2- to 7-day intervals were tested for IgG and IgM antibodies to HIV with enzyme immunoassays, Western blot testing, and radioimmunoprecipitation assays. The presence of an HIV viremic phase was demonstrated by the infectivity of plasma on normal, phytohemagglutinin-stimulated peripheral blood mononuclear cells and by the detection of HIV antigen. In 5 of these donors, HIV antigen was detected prior to or simultaneously with IgG to HIV; these HIV-antigen-positive samples overlapped an IgM immune response. The disappearance of detectable HIV antigen, and to a lesser extent plasma infectivity, was concurrent with the development of an IgG immune response. Although the improved sensitivity of a recombinant DNA-derived anti-HIV screening assay shortened the "window period" between initial HIV infection and antibody detection, HIV antigen and plasma HIV viremia were the only markers of HIV infection for several days in 2 donors. These results demonstrate that HIV plasma viremia and antigenemia occur prior to seroconversion in healthy plasma donors.

The development of AIDS or AIDS‐related conditions in a cohort of HIV antibody‐positive homosexual men during a 3‐year follow‐up period

One hundred and thirty-three homosexual men seropositive for the antibody against human immunodeficiency virus (HIV) were enrolled in a prospective study in 1984-85. The 3-year cumulative incidences of the acquired immunodeficiency syndrome (AIDS) and AIDS-related conditions, by life-table analyses, were 18% and 34%. The cumulative incidence of immune deficiency defined as CD4 lymphocytes less than 0.5 x 10(9) l-1 was 70% at 3 years. Absence of antibodies to p24 antigen, HIV antigenaemia, CD4 lymphocytes less than 0.3 x 10 l-1 and elevated serum level of IgA were significantly associated with the development of AIDS. There was no association between disease progression and persistent generalized lymphadenopathy. When adjusted to the probable year of infection, these results are in accordance with previous cohort studies. It is concluded that most, or all, subjects seropositive for HIV will develop progressive loss of CD4 lymphocytes followed by clinical signs of immune deficiency, and that differences among previous cohorts with respect to disease progression are probably due to differences in the duration of infection.

Association of human immunodeficiency virus (HIV) p24 antigenemia with decrease in CD4+ lymphocytes and onset of acquired immunodeficiency syndrome during the early phase of HIV infection

Human immunodeficiency virus (HIV) p24 antigenemia was assessed in a longitudinal study of 52 homosexual men who developed serum antibody to HIV. Antibody seroconversion to HIV as defined by a positive HIV enzyme immunoassay (EIA) confirmed by Western (immuno-) blot was associated with three major patterns of HIV antigenemia. In the first pattern, a transient antigenemia was noted 6 (six subjects) and 12 (one subject) months prior to detection of antibody by HIV EIA and Western blot in 7 (13.5%) of the 52 men. Use of an EIA employing a recombinant envelope protein (ENV9) was able to detect antibody in four of these seven men at the time of this early antigenemia. In the second pattern, HIV p24 antigenemia occurred in 8 (15.4%) of the 52 subjects within the first 12 months after HIV antibody seroconversion. No p24 antigen was detected in the 37 (71.1%) remaining subjects. CD4+ cell numbers were lower in antigen-positive men before and after antibody seroconversion. Development of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex was strongly associated with evidence of persistent p24 antigenemia during the early, postseroconversion period. HIV p24 antigenemia may be of value in determining appropriate cohorts for drug therapy trials for subjects with early-phase HIV infection.

Human immunodeficiency virus infection in sexually active wives of infected hemophilic men

Because of past multiple exposures to contaminated coagulation factor concentrates, the prevalence of human immunodeficiency virus (HIV) infection among adult hemophilic men in the United States is reported to range from 75 to 90 percent. The risk of HIV transmission through a long-term monogamous heterosexual contact can be estimated by studying the spouses of hemophilic subjects since these couples generally do not abuse intravenous drugs, usually maintain stable monogamous relationships, and are usually free of other risk factors. Our purpose was to gather data on the risk of heterosexual transmission of HIV infection in the context of long-term monogamous relations according to the duration of HIV antibody seropositivity and of HIV antigenemia in HIV-infected hemophilic men, and their sexual habits. Infection with HIV was studied in 14 sexually active spouses of infected hemophilic men who had been HIV antibody reactive for a mean of 46 +/- 23 (SD) months. One half of the hemophilic men studied had overt HIV antigenemia for a mean duration of 27 +/- 23 (SD) months; six of the men studied fulfilled clinical criteria for the diagnosis of acquired immunodeficiency syndrome (AIDS). All 14 couples were sexually active in a strictly monogamous fashion, in marriages of 13.5 +/- 10.5 (SD) years with an average reported frequency of four sexual encounters per month (range: one to 12). Plasma samples of the hemophilic husbands were retrospectively analyzed for HIV and hepatitis B virus markers. Blood samples were obtained from female spouses on at least two occasions, six months apart. Comprehensive questionnaires regarding sexual habits and other risk factors were filled out by each couple; during this interview, the couple was counseled about safe sexual practices. None of the couples studied used condoms prior to January 1986. Antibodies to HIV developed in only one of the 14 wives. At the time when this seroconversion was detected, her husband, in whom AIDS developed, had been reactive for HIV antibody for 49 months, and showed positive findings for HIV antigen for 26 months. No additional risk factors were identified for this couple. The infected female spouse, however, has a 14-year history of multiple sclerosis, and had been treated with immunosuppressant intermittently. Despite a significantly reduced number of CD4 lymphocytes, she has remained clinically asymptomatic for 17 months since seroconversion. HIV antibodies did not develop in any of the 13 remaining wives, despite the frequent practice of oral sex by six couples and reports of occasional anal intercourse by another couple.(ABSTRACT TRUNCATED AT 400 WORDS)

Persistence of Human Immunodeficiency Virus Antigenemia in Patients With the Acquired Immunodeficiency Syndrome Treated With a Reverse Transcriptase Inhibitor, Suramin

Ten homosexual men with the acquired immunodeficiency syndrome were included in a serologic follow-up study (duration, 40 weeks) of human immunodeficiency virus (HIV) antigenemia. Five of these men were treated with the reverse transcriptase inhibitor, suramin, for a period of 19 to 37 weeks. In contrast with reported changes in HIV antigen levels after treatment with zidovudine, HIV antigenemia persisted in the suramin-treated group, as well as in the untreated group. No clinical or immunologic improvement was seen in either group within the observation period. These data add evidence to the notion that monitoring HIV antigen levels helps to assess the efficacy of antiviral therapy.

Persistence of human immunodeficiency virus antigenemia in patients with the acquired immunodeficiency syndrome treated with a reverse transcriptase inhibitor, suramin. Ten-patient case-control study

• Ten homosexual men with the acquired immunodeficiency syndrome were included in a serologic follow-up study (duration, 40 weeks) of human immunodeficiency virus (HIV) antigenemia. Five of these men were treated with the reverse transcriptase inhibitor, suramin, for a period of 19 to 37 weeks. In contrast with reported changes in HIV antigen levels after treatment with zidovudine, HIV antigenemia persisted in the suramin-treated group, as well as in the untreated group. No clinical or immunologic improvement was seen in either group within the observation period. These data add evidence to the notion that monitoring HIV antigen levels helps to assess the efficacy of antiviral therapy. (<i>Arch Intern Med</i>1988;148:209-211)

Long-term evaluation of HIV antigen and antibodies to p24 and gp41 in patients with hemophilia. Potential clinical importance.

To investigate the relation between human immunodeficiency virus (HIV) antigenemia and clinical manifestations of HIV infections, we studied 96 patients with hemophilia who were positive for HIV antibody, for a median of 34 months. Every 4 to 10 months a clinical and laboratory examination was performed and serum samples were tested for three HIV markers: HIV antigen, antibody to p24, and antibody to gp41. Twenty-two subjects (23 percent) were found to be positive for HIV antigen: 8 were positive upon entry and remained so (Group 1), and 14 became positive during the study, 4 to 26 months after HIV antibody appeared (seroconversion), 13 of whom remained positive for HIV antigen (Group 2). Most subjects positive for HIV antigen had low or undetectable titers of antibody to p24, whereas the antibody titer to gp41 remained high. In Group 2, patients with low p24 antibody titers had further decreases in their titers before or at the time HIV antigen appeared. Once present, HIV antigen persisted and tended to increase in concentration. In contrast to Group 3 (negative for HIV antigen, low anti-p24 titer) and 4 (negative for HIV antigen, high anti-p24 titer), the groups positive for HIV antigen had significantly higher incidences of acquired immunodeficiency syndrome (P = 0.05), immunodeficiency-related infections (P less than 0.001), and immune thrombocytopenia (P = 0.001), and had more severe disease as measured by the Walter Reed staging system (P less than 0.001). In this study, HIV antigen appeared to be a better predictive marker of HIV-related complications than the absolute T4+ count. These results suggest that HIV antigenemia indicates a poor clinical prognosis.

Risk of AIDS related complex and AIDS in homosexual men with persistent HIV antigenaemia.

One hundred and ninety eight men seropositive for human immunodeficiency virus (HIV) antibody and 58 HIV antibody seroconverters were studied for an average of 19.3 (SEM 0.5) months to assess the relation between HIV antigenaemia and the risk of developing the acquired immune deficiency syndrome (AIDS) and AIDS related complex. Forty (20.2%) of the 198 HIV antibody seropositive men were antigen positive at entry and remained so during follow up. Eight (13.8%) of the 58 HIV antibody seroconverters and 20 (12.7%) of the remaining 158 HIV antibody seropositive men became antigen positive during follow up, resulting in an end point attack rate for HIV antigenaemia of 14.3%. AIDS related complex was diagnosed in 25 (15.8%) of the HIV antigen negative men and in 14 (20.7%) of the HIV antigen positive men. AIDS was diagnosed in 15 men, resulting in an end point attack rate for AIDS of 23.9% in the HIV antigen positive group and 1.3% in the antigen negative group. HIV antibody seropositive men without symptoms but with persistent HIV antigenaemia are at increased risk of developing AIDS and AIDS related complex.

Human Immunodeficiency Virus Antigenemia

The article by Kessler et al 1 in this issue ofThe Journaldescribes the acute illness associated with human immunodeficiency virus (HIV) infection in four individuals. Of interest was the detection of HIV antigenemia during the course of this self-limited illness before enzyme-linked immunosorbent and Western blot assays for antibody to HIV became positive. The presence of circulating antigen thus helped to establish the diagnosis. Other investigators 2 have reported that HIV antigenemia precedes seroconversion in an unknown proportion of acutely infected individuals. The evidence available to date suggests that the circulating antigen contains the core protein of the HIV (p24) and possibly other epitopes of the virus, and that when antibody to the p24 component of the virus increases to measurable concentrations in serum or plasma, the antigen can no longer be detected. 3 In some individuals, months to years after infection, anti-p24 concentrations fall in association with

LONG LATENCY PRECEDES OVERT SEROCONVERSION IN SEXUALLY TRANSMITTED HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

Signs of latent HIV infection were sought in stored serum samples collected before overt seroconversion, confirmed by enzyme-linked immunosorbent assay (ELISA), from 9 subjects with human-immunodeficiency-virus (HIV) infection, in serum from 25 seronegative sexual partners of HIV-seropositive men and from 23 other seronegative, homosexually active men. Free HIV antigen and/or low-titre antibodies to recombinant structural (core, env) or non-structural (3'orf, sor, tat) proteins were seen 6-14 months before seroconversion in all 9 subjects who seroconverted. Antibodies against core proteins detected by western blot were usually the first sign of latent HIV infection. 5 of the 25 ELISA-negative exposed partners have shown HIV antigenaemia and antibodies against core proteins for 16-34 months. By in-situ hybridisation, HIV-specific RNA was detected in peripheral-blood non-lymphoid mononuclear cells in some of the latently infected partners. All subjects with latent HIV infection had normal numbers of T4 lymphocytes but half of them lost their in-vitro proliferative T-cell response to a recall antigen (purified protein derivative of tuberculin). Early HIV infection, characterised by a low-level and restricted antibody response towards HIV core and regulatory proteins, seems mainly to affect antigen-presenting cells.

Pathogenesis of HIV and its implications for serodiagnosis and monitoring of antiviral therapy

Human immunodeficiency virus (HIV) is lymphotropic and neurotropic. In vivo clinical and immunological abnormalities develop in a large proportion of long-term HIV antibody seropositive persons. Different stages of HIV infection are marked by expression of HIV genes, production of HIV antibodies, formation of antigen/antibody complexes and clearance of such complexes. Transient HIV antigenemia appearing generally 6–8 wk prior to HIV antibody (HIV-Ab) seroconversion and lasting 3–4 mth is generally seen in acute infection. IgM antibodies predominantly to core proteins may occasionally be detectable when, or just before, IgG antibodies appear. If IgG antibodies to both envelope and core proteins persist in the absence of HIV-Ag the short-term prognosis is relatively good. However, HIV-Ag seroconversion may appear at any time after HIV-Ab seroconversion. Progression to AIDS is strongly associated with declining or absent levels of IgG antibodies to p24. IgG2 and IgG4 antibodies to HIV, which are mainly directed to p24, disappear most dramatically. Titers of antibodies to HIV p24 below 64 are strongly associated with the presence of HIV antigen and a poor clinical outcome.

Persistent HIV antigenaemia and decline of HIV core antibodies associated with transition to AIDS.

Sequential serum samples from 13 homosexual men who seroconverted for antibodies to human immunodeficiency virus (HIV) were tested for HIV antigen. In one of these men, who developed the acquired immune deficiency syndrome (AIDS), HIV antigenaemia preceded the onset of AIDS by more than a year and persisted throughout the course of the disease. This antigenaemia was accompanied by the disappearance of IgG antibody reactivity to the major HIV core protein p24. In none of the 12 others, who all remained without serious disease, were serum concentrations of HIV antigen detected, except on one occasion in one man. All their serum samples showed strong IgG antibody reactivity to p24. Nine children who were infected with HIV in 1981 by plasma transfusion from a single donor were also followed up for HIV antigenaemia. HIV antigen was almost constantly present in the serum (26 of 28 samples) of five children who developed AIDS related complex or AIDS and less often in the serum (four of 10 samples) of four children who remained free of symptoms. The two children who developed AIDS showed a virtual absence of antibody reactivity to p24. These results indicate that increased HIV gene expression is a contributing factor to the development of AIDS and also provide evidence for a switch from latent to active HIV infection.