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Risk factors for HIV-1 seroconversion among young men in northern Thailand.

OBJECTIVE: To identify behavioral and sociodemographic risk factors for incident human immunodeficiency virus-1 (HIV-1) infection among healthy young men in northern Thailand. DESIGN: Men inducted into military service in northern Thailand in May and November 1991 were followed at 6-month intervals until discharge 2 years later. Trained nonmilitary interviewers identified risk factors for HIV-1 infection through interviews with the men. SETTING: Thirteen military bases in northern Thailand. PARTICIPANTS: A total of 1932 seronegative men, aged 19 to 23 years (average age, 21 years) at enrollment, conscripted into the Royal Thai Army and Air Force from six upper-northern Thai provinces. MAIN OUTCOME MEASURES: Human immunodeficiency virus-1 seroincidence as determined through enzyme-linked immunosorbent assay and verified by Western blot, and univariate and multivariate analyses of risk factors related to HIV-1 incidence. RESULTS: A total of 85 men seroconverted to HIV-1 over the period of observation, giving an incidence rate of 2.43 per 100 person-years. Factors strongly associated with HIV-1 seroconversion were frequency of visits to female commercial sex workers (CSWs), sex with men, and incident sexually transmitted diseases (STDs). High frequency of condom use showed a significant (P < .001) protective effect for HIV-1 incidence among men with a history of recent sex with female CSWs in univariate analysis, but a multivariate model demonstrated no difference in HIV-1 seroconversion rates by consistency of condom use. Multivariate analysis incorporating condom use showed that having sex with men (adjusted relative risk [RR], 2.59; 95% confidence interval [CI], 1.08 to 6.25), having sex with CSWs (adjusted RR ranged from 2.54 [95% CI, 1.81 to 3.58] to 2.74 [95% CI, 1.56 to 4.81]), and incident STDs (adjusted RR, 2.38 [95%, CI, 1.31 to 4.32]) to be predictors of incident HIV-1 infection. Substance use was not associated with HIV-1 seroconversion rates in multivariate analysis. CONCLUSION: The HIV-1 incidence in this cohort of young men appears to be primarily attributable to having sex with female CSWs. Condom use provided some protection, although not in multivariate analysis; however, condom use has previously been shown likely to be useful in preventing HIV-1 transmission. Thus, programs to increase effective condom use in brothels are essential. Efforts to extend condom use to non-CSW partners are especially needed. More effective prevention and treatment of STDs may also be necessary to decrease HIV-1 infection in this population.

AIDS Serodiagnosis↗

[The clinical manifestations of HIV infection during seroconversion].

21 seroconversion HIV-infected subjects have been examined. 16 of them presented with acute symptoms. The disease in the period of seroconversion manifested with fever, weakness, headache, pain in the throat, enlargement of peripheral lymph nodes, polymorphous eruption. Typical mononucleosis-like syndrome occurred in 3 patients only. Half of the patients had subclinical disease, no eruption was seen. Because of clinical indications only 8 of 21 patients were examined for HIV infection. One-third of the patients in seroconversion had moderate thrombocytopenia, probably of autoimmune nature. Autoimmune disorder of the thyroid was registered in 1 patient. The diagnosis of acute HIV infection is not easy in view of rare occurrence of immunodeficiency typical for this infection. Candidiasis of the mucosa was seen in 37.5%, low levels of CD4-lymphocytes in 66.7% of the cases.

AIDS-Related Opportunistic Infections↗

Is AIDS a floating point between HIV seroconversion and death? Insights from the Tricontinental Seroconverter Study.

OBJECTIVE: To investigate the significance of the time from seroconversion to AIDS (incubation time) and other covariates for survival from AIDS to death. METHODS: In survival analysis, survival from AIDS to death was compared for different categories of length of incubation time adjusted and unadjusted for other covariates, and significant predictors for survival from AIDS to death were investigated. RESULTS: Survival after AIDS was not affected by the incubation time in univariate as well as in multivariate analyses. Predictive factors for progression from AIDS to death were age at seroconversion, type of AIDS diagnosis, and CD4 cell count at AIDS. The relative hazard for age at seroconversion increased 1.38-fold over 10 years. Men with a CD4 cell count at AIDS of <130 x 10(6)/l had a twofold higher risk in progression to death than men with higher CD4 cell counts. Persons diagnosed with lymphoma had a sixfold higher risk of progression to death than persons with Kaposi's sarcoma or opportunistic infections. CONCLUSIONS: The incubation time as well as other factors before AIDS did not affect survival after AIDS. Survival from AIDS to death can be predicted by data obtained at the time of AIDS diagnosis, such as type of diagnosis, age and CD4 cell count. AIDS seems to be a significant point in progression to death, and not just a floating point between infection and death affected by prior factors for persons who did not receive effective therapy and did not have long incubation times.

Acquired Immunodeficiency Syndrome↗

Determinants of progression of HIV infection in a Greek hemophilia cohort followed for up to 16 years after seroconversion.

Our objectives are to describe the progression of HIV disease and to assess the influence of hemophilia-related variables, age at infection, and antibodies to cytomegalovirus infection (anti-CMV) in a Greek cohort of 158 HIV-1-positive hemophilic men, who received prospective follow-up for up to 16 years after infection. A total of 79 patients had died, representing a cumulative progression rate of 72.4% (95% confidence interval [CI], 56.6-83.3). A significant proportion of the mortality (30%) resulted from conditions not formally related to AIDS, with liver failure and cerebral hemorrhage predominant. At 16 years after seroconversion, 66 patients had developed clinical AIDS, a cumulative progression rate of 58.2% (95% CI, 47.1%-86.3%) whereas 15 years after infection 81.5% (95% CI, 74.2%-87.9%) of the patients had AIDS or a CD4 cell count <200 cells/mm3. Hemophilia-related variables or presence of anti-CMV were not significantly associated with disease progression. Age at infection was a strong prognostic factor for all three endpoints. Appropriate modeling showed a nonlinear age effect, with a steeper increase of relative hazard for patients >40 years of age at seroconversion. The age effect remained significant even after controlling for current CD4 cell count. Further investigation is required to elucidate the mechanisms of the age effect and the contribution of HCV coinfection on the disease progression.

Adolescent↗

Impact of tuberculosis on HIV disease progression in persons with well-documented time of HIV seroconversion.

Tuberculosis (TB) enhances HIV replication in vitro, but its impact on HIV progression at the population level is not established. Studies from industrialized and nonindustrialized countries show contradictory results as to whether TB accelerates HIV progression, although no studies have been conducted in persons with well-documented seroconversion times. Data from HIV seroconverters from 19 cohorts were analyzed to examine the effect of TB on HIV progression comparing persons with TB and persons without TB infected by HIV for the same length of time. TB and other AIDS-defining conditions (ADCs) were fitted as time-dependent covariates, adjusting for age, sex, transmission category, calendar year at risk, and cohort, using Cox proportional hazards models and allowing for late entry. Of 4398 seroconverters, 1294 (29%) developed AIDS. TB accounted for 72 (5.6%) of initial ADCs and for 105 (5.7%) of all ADCs. Survival from HIV seroconversion shows that compared with AIDS-free subjects, the risk of death associated with TB as an initial ADC (hazard ratio [HR] = 23.23, 95% CI: 14.60-36.96) does not differ from that associated with Kaposi sarcoma (HR = 23.47, 95% CI: 16.66-33.05) or esophageal candidiasis (OC)/Pneumocystis carinii pneumonia (PCP) (HR = 30.97, 95% CI: 24.38-39.34) but is lower than that for opportunistic infections other than TB, OC/PCP (HR = 46.83, 95% CI: 37.86-47.94) and high-grade non-Hodgkin lymphomas/invasive cervical carcinoma (HR = 92.71, 95% CI: 60.83-141.3). The lowest risk of death was seen, as expected, in AIDS-free subjects. HIV progression is not inherently faster in subjects who develop TB compared with other individuals with AIDS who have been infected by HIV for the same length of time in countries where TB treatment is widely available.

AIDS-Related Opportunistic Infections↗

Cancer incidence in a cohort of human immunodeficiency virus seroconverters. HIV Italian Seroconversion Study Group.

BACKGROUND: In addition to Kaposi's sarcoma and non-Hodgkin's lymphomas, it has been postulated that human immunodeficiency virus (HIV) infection may increase the risk of other cancers. The aim of the current study was to compare incidence rates of cancer among individuals who seroconverted for HIV infection with the rates in the general population of Italy. METHODS: This study is part of an ongoing cohort investigation conducted by the HIV Italian Seroconversion Study Group. The study has enrolled 1255 individuals (906 males and 349 females) between the ages of 20 and 49 years who are at risk for HIV infection and have had a documented negative HIV test followed by a positive test. For each individual, the midpoint in time between the negative and positive tests was used to estimate the seroconversion date. The person-years at risk for cancer were then computed from the midpoint date to the last follow-up date or to death, and the number of cases of cancer observed in the cohort was compared with the expected number, based on rates among the general population of the same age and gender. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were computed. RESULTS: A total of 58 cases of cancer were observed in the cohort. In comparison with rates in the general population, Kaposi's sarcoma was 1051 times more frequent, and non-Hodgkin's lymphomas were 157 times more frequent. Hodgkin's disease was observed in 3 men (i.e., 38 times more often in the cohort of HIV seroconverters [95% CI, 8-111]), in particular among homosexual men (SIR = 103). One woman developed stomach carcinoma. CONCLUSIONS: The findings of the current incidence study are in agreement with previous studies showing excesses of Kaposi's sarcoma and non-Hodgkin's lymphomas in HIV-positive individuals. In addition, the findings suggest an association of HIV infection with Hodgkin's disease. Whether Hodgkin's disease in HIV-infected individuals should be considered an AIDS-defining illness is a question that is worthy of attention.

Adult↗

Acute T-cell leukemia/lymphoma mimicking Hodgkin's disease with secondary HTLV I seroconversion.

The authors observed a pleiomorphic lymphoma mimicking Hodgkin's lymphoma in a French Guyana black woman lacking antibodies for human T-cell lymphoma/leukemia virus type I (HTLV I). After two courses of chemotherapy with either mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vincaleukoblastine, and dacarbazine (ABVD), a typical acute T-cell leukemia/lymphoma developed with HTLV I seroconversion. Specific HTLV I DNA sequences were detected using the polymerase chain reaction (PCR) on a lymph node biopsy obtained before chemotherapy. The mechanisms of the seroconversion are discussed.

Adult↗

Plasma adenosine deaminase2 is a marker for human immunodeficiency virus-1 seroconversion.

Plasma adenosine deaminase2 (ADA2) has recently been proposed to be a marker for human immunodeficiency virus-1 (HIV) infection. We measured ADA2 levels in plasma from two groups of white homosexual males at 6-month intervals for a total of 2.5 years. One group consisted of 6 subjects who seroconverted for HIV, and the other consisted of 8 HIV seropositive patients who progressed from asymptomatic (CDC Groups II/III) to symptomatic (CDC Group IV) disease. Seroconversion was associated with a significant increase in plasma ADA2 which persisted throughout follow-up of 1.5 years. However, disease progression in HIV seropositive patients was not associated with any significant change in plasma ADA2. In conclusion, ADA2 may represent a unique marker for HIV seroconversion which does not change with later progression to symptomatic disease.

Adenosine Deaminase↗

Hepatitis C virus seroconversion rate in established blood donors.

The results of hepatitis C virus (HCV) antibody test of 237,813 blood donations collected from 143,815 donors by the West Midlands Blood Transfusion Centre in 1993 were analyzed retrospectively in order to determine the seroconversion rate among established previously anti-HCV negative donors. Three hundred sixteen (0.22%; 1 in 455) donors were positive by the enzyme linked immunosorbent assay (ELISA) screening test and 34 (0.024%; 1 in 4,230) donors were positive by ELISA and the Recombinant Immuno Blot Assay (RIBA). Three donors previously negative for HCV antibody reacted positively by both tests. The annual seroconversion rate was calculated as one in 35,937 donors. This figure argues against limitation of HCV antibody screening to new blood donors. A further 45 donors negative on previous screening reacted positively by ELISA and were indeterminate by RIBA. Unexpectedly, lapsed blood donors first tested for HCV antibody in 1993 had high positive reaction rates by ELISA and RIBA, which was significantly (P < 0.001) higher than those of new donors. RIBA-positive reaction rate among ELISA-positive donors was significantly higher amongst males than females (P < 0.001).

Adult↗

Estimating the distribution of times from HIV seroconversion to AIDS using multiple imputation. Multicentre AIDS Cohort Study.

Multiple imputation is a model based technique for handling missing data problems. In this application we use the technique to estimate the distribution of times from HIV seroconversion to AIDS diagnosis with data from a cohort study of 4954 homosexual men with 4 years of follow-up. In this example the missing data are the dates of diagnosis with AIDS. The imputation procedure is performed in two stages. In the first stage, we estimate the residual AIDS-free time distribution as a function of covariates measured on the study participants with data provided by the participants who were seropositive at study entry. Specifically, we assume the residual AIDS-free times follow a log-normal regression model that depends on the covariates measured at enrolment on the seropositive participants. In the second stage we impute the date of AIDS diagnosis for the participants who seroconverted during the course of the study and are AIDS-free with use of the log-normal distribution estimated in the first stage and the covariates from each seroconverter's latest visit. The estimated proportions developing AIDS within 4 and within 7 years of seroconversion are 15 and 36 per cent respectively, with associated 95 per cent confidence intervals of (10, 21) and (26, 47) per cent. We discuss the Bayesian foundations of the multiple imputation technique and the statistical and scientific assumptions.

AIDS Serodiagnosis↗

Characterization of a linear epitope in the nonstructural region 4 of hepatitis C virus with reactivity to seroconversion antibodies.

Mapping and possible diagnostic meaning of a highly conserved, linear NS4 epitope (NS4/3), located outside the C100-3 antigen within the carboxyl terminal proportion of the NS4 region, with major immunoreactivity with specimens of patients with HCV infection from various geographic origins is described. Transient, acute-phase IgM anti-HCV NS4/3 was detected coincidentally or earlier than active IgG anti-HCV NS4/3 response with four well-characterized seroconversion panels. GenBank alignment studies identified patch homologies between the NS4/3 sequence and a number of non-HCV proteins, which may explain part of the cross-reactivity of the NS4/3 epitope. Some of the "false positive reactivities" of the NS4/3 epitope with asymptomatic blood donors, not being confirmed with FDA-approved anti-HCV assays without the NS4/3 epitope, may be explained by recognition of very early seroconversion antibodies.

Amino Acid Sequence↗

Chronic immune thrombocytopenic purpura--immunological analyses of a patient pre- and post-HIV seroconversion.

A seven year follow-up of immune parameters is reported for a patient with chronic immune thrombocytopenic purpura (ITP) pre and post human immunodeficiency virus (HIV) seroconversion. Therapies such as intravenous IgG, prednisone, vincristine, or Ciclosporin A had no clear-cut beneficial effect on platelet counts. A long-term normalization of platelet counts was achieved by splenectomy. At splenectomy the patient was seropositive for HIV, most likely transmitted by blood products received half a year prior to laparatomy. Mean plasma levels of the second component of complement, C2, were half of the normal values prior to and within the lowest normal range post HIV seroconversion. Nevertheless, the T cell-dependent B cell response to HIV, which is dependent on the activation of C3 via the classical pathway of complement, was normal: Western blot analysis of total IgG and of IgG subclass responses to individual HIV antigens proved to be unimpaired.

Antigen-Antibody Complex↗

Seroconversion to hepatitis C virus antibodies in patients with acute posttransfusion non-A, non-B hepatitis in Sweden.

Seventy-four patients in 1978 and 316 in 1986, all transfused during open-heart surgery in Stockholm, Sweden, were studied prospectively for the development of posttransfusion non-A, non-B (NANB) hepatitis, seroconversion to hepatitis C virus antibodies (anti-HCV) (C-100), time lag to seroconversion to anti-HCV and outcome of posttransfusion NANB/C hepatitis. Anti-HCV was tested up to six months after transfusions in patients from 1978 and up to one year after transfusions in patients from 1986. Fifty-four percent of the patients who developed posttransfusion NANB hepatitis seroconverted to anti-HCV, 7/15 (47%) in 1978 and 8/13 (62%) in 1986. Four (27%) of the 15 patients who seroconverted to anti-HCV were anti-HCV reactive within one week, 12 (80%) within eight weeks and all within 18 weeks after the onset of hepatitis. The ELISA optical density/cut-off (OD/CO) ratio was above 4.0 in all patients with hepatitis C who seroconverted. One transfused patient with normal serum aminotransferase levels throughout follow-up seroconverted after six months. He had a temporary positive anti-HCV reactivity with a maximal ELISA OD/CO ratio for anti-HCV of only 1.2, which became negative three years later. Development of chronic hepatitis was noticed in 9/15 (60%) patients who seroconverted to anti-HCV and in 5/13 (38%) patients with posttransfusion NANB hepatitis who did not seroconvert.

Acute Disease↗

Serological study of subjects with seroconversion to human immunodeficiency virus.

Twelve homosexual males who seroconverted to human immunodeficiency virus (HIV) were followed-up for over two years. Analysis of sera by immunoblotting showed that seroconversion was characterized by the presence of specific IgM that reacted mainly with viral polypeptides of molecular weights ranging from 17 Kd to 55 Kd. Specific IgG to all HIV proteins was detected. Immunoblotting showed that antibodies to 24 Kd core protein alone or in association with 17 Kd polypeptide appeared first in some cases. Virus antigen was detected in six patients: five subjects were positive at the time of seroconversion, and one became positive afterwards. It is concluded that detection of IgG and IgM antibody against the different viral polypeptides, together with detection of viral antigen is necessary in order to determine the stage of HIV infection.

Acquired Immunodeficiency Syndrome↗

[Acute primary stage of HIV infection with documented seroconversion].

We report a 34-year-old homosexual man who developed a maculopapular, non-itchy exanthema mainly on the trunk in addition to fever up to 39.8 degrees C, general malaise, arthralgias, generalized enlargement of the lymph nodes, watery diarrhoea and weight loss. The patient was in an acute phase of the HIV infection according to standards of WHO and CDC (i.e. acute infection with duration from 3 days to 3 weeks with occasional mononucleosis-like symptoms and positive antibody tests). We documented the seroconversion from HIV-negativity to HIV-positivity 15 days after the onset of the acute illness, concomitant with the resolution of the clinical symptoms. Haematological changes were monitored during the conversion. The infection with HIV-1 was shown by the reduction of T4 helper cells (262/microliters) and the inversion of the CD4:CD8 ratio (< 0.5 during seroconversion). The patient also developed generalized candidiasis owing to the acute immunodeficiency.

AIDS-Related Opportunistic Infections↗

Early reduction of infected hepatocytes by activated immunity at the time of interferon withdrawal hepatitis followed by lamivudine administration resulted in higher seroconversion in hepatitis Be antigen-positive patients with chronic hepatitis B.

BACKGROUND: It has been found that the efficacy of lamivudine (LAM) therapy can be improved by preceding administration with a short course of corticosteroid that induces a flare of the disease upon its withdrawal. Because of the side effects of corticosteroid, we tested the effect of a short course of interferon (IFN) as the primer instead of prednisolone, which was followed by LAM when the hepatitis flare occurred. The incidence of LAM resistance mutations and the effect of core promoter and precore mutations on the durability of the responses were also studied. METHODS: Patients treated with interferon (IFN)-LAM therapy (n=73) were compared to those treated with IFN alone (n=117). The IFN-LAM group received IFN-alpha MU/day, t.i.w. for a 3-month period. LAM (10mg/day during 1 year) was started when IFN withdrawal hepatitis occurred during 2-10 months after stopping IFN. The LAM-resistant, core promoter, and precore mutations were examined by sequencing. RESULTS: (1) The IFN-LAM group developed exacerbated hepatitis following IFN withdrawal in 63 patients before starting LAM therapy. The seroconversion (SC) rate was significantly higher in the IFN-LAM group than in the IFN-alone group (61% vs 26%, P=0.0001). (2) The LAM resistance mutation rate was 31% at 1 year after initiating LAM therapy. (3) In a stepwise discriminant-function analysis, decreased level of HBeAg determined at 4 weeks after LAM administration and increased level of HBeAb before the start of LAM administration contributed significantly on seroconversion to anti-HBe (P = 0.0073 and 0.004, respectively). (4) The reappearance rate of HBeAg within 6 months after the therapy (relapse) was 33% in the IFN-LAM group and 10% in the IFN-alone group. The prevalence of core promoter and precore mutations did not change before and after the therapy, nor did these mutations correlate with the relapse after stopping IFN-LAM therapy. CONCLUSIONS: (1) Our findings suggest that early reduction of infected hepatocytes expressed by HBeAg by LAM may contribute to a high SC rate of IFN-LAM therapy. (2) The emergence of LAM-resistant mutations was similar to the previously reported rate, and neither core promoter nor precore mutations correlated with relapse of seroconverters after IFN-LAM withdrawal.

Adult↗

Congestive heart failure and myocarditis after seroconversion for toxoplasmosis in two immunocompetent patients.

Two cases of myocarditis and congestive heart failure in immunocompetent patients with seroconversion for toxoplasmosis are reported. Serological tests showed that in the first case the cardiac manifestations occurred at the time of seroconversion (low IgG, raised IgM and IgA), whereas in the second case they occurred several months after the initial infection when IgM was decreasing, IgG levels were very high (>1000 IU/ml) and IgG had high affinity for the antigen. The pathophysiological mechanisms underlying cardiac involvement in acute or chronic toxoplasmosis are discussed.

Adult↗

Late seroconversion following HPV-77, DE5 rubella virus vaccine.

The HAI antibody responses to HPV-77, DE5 rubella virus vaccine were evaluated with respect to time in 258 rubella-susceptible children. Seroconversion after 28 days post inoculation with this vaccine was not uncommon. These findings indicate a greater degree of modification of the HPV-77, DE5 rubella virus vaccine since most vaccines have been shown to seroconvert by 28 or 30 days post inoculation with the HPV-77 and other HPV-77 derived rubella vaccines. With respect to the routine of inoculating rubella-susceptible women in the childbearing age, late seroconversion could be of importance because of this uncertainty of the time of viremia and the increased chane of pregnancy with increasing time following immunization. Comparative information is needed for the Cendehill and candidate RA 27/3 rubella virus vaccines. That vaccine showing an early and predictable higher conversion ratio would be the most desirable for use in the above population.

Antibodies, Viral↗