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[The prognostic significance of the clinical manifestations of HIV infection during seroconversion].

For the period 1990-1993, HIV infection in seroconversion was diagnosed in Russia in 21 cases. Of them, 16 patients had acute symptoms. Follow-up results are available for 12 patients in seroconversion who had either typical or obscure symptoms (6 and 6 patients, respectively). It is found that the disease progresses more rapidly in patients with the history of acute HIV infection in seroconversion manifesting with clear-cut typical symptoms of 4-week duration, at least. One patient from this group 3 years and 7 months after seroconversion developed Kaposi's sarcoma and candidiasis esophagitis which indicates the occurrence of AIDS stage IIIB.

Acute Disease↗

Seroconversion rates to combined measles-mumps-rubella-varicella vaccine of children with upper respiratory tract infection.

OBJECTIVE: To determine if upper respiratory tract infection (URI) affects the seroconversion rate or quantitative response to each component of a combined measles-mumps-rubella-varicella vaccine. SUBJECTS AND METHODS: One hundred forty-nine children between 15 and 18 months of age were prospectively divided into two groups according to the presence of URI or recent history of URI symptoms within the 4 weeks before vaccination. Once stratified, 74 children in the healthy group and 75 children in the URI group were randomly assigned to receive one of three lots of measles-mumps-rubella varicella vaccine by subcutaneous injection into the deltoid area. Serum was obtained from each child just before vaccination and 4 to 6 weeks later for measuring antibody levels against each virus. RESULTS: Prevaccination antibody levels against each virus in the URI and healthy groups did not differ. Nine children had pre-existing antibodies to varicella and six to mumps; no child had positive serologies for measles or rubella before vaccination. Children with pre-existing antibody were excluded from analysis of seroconversion for that virus. Seroconversion to measles, mumps, and rubella occurred in 100% of children in both groups. Mean antibody levels did not differ between the healthy and URI groups for measles (111 vs 122), mumps (97 vs 108), or rubella (96 vs 102). Three (4%) of 70 children with URIs in whom varicella serologies were available failed to seroconvert to varicella vaccine although none of the 69 healthy children had vaccine failure (P = .24). The mean varicella antibody level was 11.3 +/- 1.4 in the healthy children, which did not differ significantly from the level of 9.5 +/- 0.9 in the URI group. CONCLUSIONS: Seroconversion to measles, mumps, rubella, and varicella was not significantly affected by the presence of a concurrent or recent URI in 15- to 18-month-old children.

Antibodies, Viral↗

CD4 lymphocyte counts within 24 months of human immunodeficiency virus seroconversion. Findings in the US Navy and Marine Corps. The Navy Retroviral Working Group.

BACKGROUND: Although CD4 lymphocytes are the primary target of the human immunodeficiency virus (HIV), few studies have evaluated CD4 cell counts in a large population of seroconverters with known dates of seroconversion. This study reports an analysis of CD4 lymphocyte counts and CD4 cells as a percentage of all lymphocytes within 24 months of estimated date of HIV seroconversion in 1046 HIV seroconverters. METHODS: Study participants included all Navy and Marine Corps seroconverters (1023 men, 23 women) from 1987 through 1991 with a previous negative HIV test. CD4 lymphocyte counts and percentages were obtained for blood drawn from HIV seroconverters during initial clinical evaluations carried out at Naval Medical Centers in Bethesda, Md; Oakland, Calif; Portsmouth, Va; and San Diego, Calif. The seroconversion date was estimated as the midpoint between the last negative test date and the first positive test date. RESULTS: Nearly 40% of seroconverters presented with initial CD4 lymphocyte counts lower than 0.50 x 10(9)/L (500/microL) and 3% with counts lower than 0.20 x 10(9)/L (200/microL). Approximately half the seroconverters presented with fewer than 29% CD4 cells, and 5% presented with fewer than 14% CD4 cells. There were no significant differences in CD4 counts according to sex, race, or estimated duration of HIV infection. CONCLUSIONS: Little difference in CD4 lymphocyte counts or percentages by duration of infection within 24 months was evident on initial clinical evaluation of HIV seroconverters. The high percentage of seroconverters presenting with low CD4 counts or percentages suggests a population of seroconverters with rapid depletion of CD4 lymphocytes following seroconversion.

Adolescent↗

Role of nutritional status and weight loss in HIV seroconversion among Rwandan women.

To investigate nutritional status and heterosexual human immunodeficiency virus (HIV) transmission, we performed a nested case-control study of sexually active, adult women in Kigali, Rwanda. Forty-five women who seroconverted during the 24-month study period were compared to 74 women who remained seronegative throughout the study. Seroconvertors and nonseroconvertors did not differ in preseroconversion serum levels of vitamin A, carotenoids, vitamin E, selenium, albumin, ferritin, or cholesterol. Weight loss, however, was a significant predictor of eventual HIV seroconversion. Subsequent seroconvertors lost an average of 1.5 kg during the first 6 months of the study compared with a 1.0-kg gain (p = 0.001) for nonconvertors. Nine of 27 (33%) seroconvertors, compared with one of 44 (2%) controls, lost at least 5 kg in the 6-month period beginning 1 year before their seroconversion (odds ratio, 21.5, 95% confidence interval 4.1-112). The association between weight loss and seroconversion was independent of other potential risk factors such as socioeconomic status, pregnancy, and genital ulcer disease. In addition to these findings for measured weight loss during follow-up, reported weight loss before enrollment was also a risk factor for subsequent seroconversion. Additional studies of heterosexual HIV transmission are needed to determine whether or not weight loss is causally related to susceptibility for HIV infection.

Adolescent↗

[Clinico-prognostic significance of partial seroconversion in chronic viral hepatitis B follow-up. Wartenbert Study (1974-1994), II].

146 patients (62 female, 84 male) with chronic hepatitis B were regularly examined in 1 to 2 year intervals with an average follow-up period of 12 years (means). Each time patients were evaluated by physical examination, routine laboratory data, immunological and serological testing, ultrasonography, and laparoscopy and/or percutaneous liver biopsy. No patient of the study underwent immunosuppressive or antiviral treatment at any time. The average time data in years and months are given as the median value (mean). Frequency and date of seroconversion from HBeAg to anti-HBe after the first diagnosis of HBV-infection: in patients with chronic persistent hepatitis (CPH) in 79% of cases after 8 years, in patients with chronic active hepatitis (CAH) in 72% of cases after 7 years, and in patients with liver cirrhosis in 61% of cases after 9 years. The overall seroconversion rate in all patients with chronic hepatitis B amounted to 68% 8.5 years after the first diagnosis of HBV-infection. Clinical and prognostic significance: The seroconversion from HBeAg to anti-HBe mostly led to substantial and sustained biochemical and histologic resolution of liver disease activity. In patients with CPH in 100% of cases after 15 months, in patients with CAH in 87% of cases after 17 months, and in patients with liver cirrhosis in 64% of cases after 2.5 years. 80% of these patients with seroconversion and histologic recovery remained HBV-DNA (PCR)-positive.

Adult↗

Low seroconversion with hepatitis B vaccination in peritoneal dialysis patients.

OBJECTIVE: To compare seroconversion using hepatitis B vaccine between hemodialysis (HD) and peritoneal dialysis (PD) patients. DESIGN: Data on PD patients vaccinated were collected retrospectively for the period 1992 to 1995. The data on HD patients were collected prospectively from 1991 to 1994. SETTING: A university outpatient dialysis center. PARTICIPANTS: All adult patients who received all four doses of hepatitis B vaccine while on dialysis were included (47 PD and 50 HD patients). INTERVENTION: Recombinant hepatitis B vaccine (Engerix), 40 micrograms IM was administered at 0, 1, 2, and 6 months. MAIN OUTCOME MEASURE: Seroconversion was measured after completion of the vaccination series. RESULTS: 74% of the HD patients seroconverted compared to 53% of PD patients (p = 0.03). Older, heavier patients compared to all the other patients had a lower seroconversion rate in both the HD patients (55% vs. 78 %) and PD patients (38% vs. 59%) (p = 0.03). CONCLUSION: The seroconversion rate to recombinant hepatitis B vaccine is lower in patients on PD than on HD for unclear reasons. Further studies are required to determine the etiology of this difference.

Adult↗

HIV seroconversion among factory workers in Harare: who is getting newly infected?

OBJECTIVE: Zimbabwe, like other countries in sub-Saharan Africa, is experiencing a rapidly growing HIV/AIDS epidemic. It is crucial to determine risk events and socio-demographic characteristics associated with incident infections in order to tailor prevention messages accordingly. A cohort was established among factory workers with the objectives of estimating HIV incidence, seroprevalence, correlates of infection and subsequently evaluating the impact of prevention interventions. SETTING: 40 factories in Harare, Zimbabwe. DESIGN AND METHODS: HIV seroindicence [total new infections over person time (years) follow up] was estimated in a longitudinal cohort of male factory workers before and during a randomised peer education intervention. Correlates of seroconversion were identified using Cox regression analysis. RESULTS: Of 2,992 subjects enrolled there were 129 seroconversions during 1993 to 1996 follow up, yielding a 2.96 per 100 person year (PY) seroconversion incidence (95% CI = 2.47 to 3.52). Reporting a genital ulcer during follow up (Hazard ratio [HR] = 4.9, p = 0.001) having multiple sexual partners (HR = 1.9, p = 0.04), having a urethral discharge (HR = 2.1, p = 0.001), being single (HR = 2.3, p = 0.001), widowed or married but not residing with wife were independent factors significantly associated with risk of HIV seroconversion. CONCLUSIONS: Incidence of HIV identified in this economically productive sector is unacceptably high, and, disturbingly, is increasing in some age groups. Although the impact of the present intervention remains to be evaluated, the high incidence of HIV infection, points to the need for a more aggressive prevention effort in the general population.

Adult↗

Reduced seroconversion to measles in infants given vitamin A with measles vaccination.

Administration of 100,000 IU vitamin A at the time of measles immunisation is currently recommended for infants in developing countries. However, the safety and value of giving vitamin A, a potent immune enhancer, with live measles virus vaccines are unknown. We conducted a randomised, double-blind, placebo-controlled clinical trial in Indonesia to evaluate the effect of simultaneous vitamin A supplementation on the immune response to measles immunisation at six months of age. 336 infants received either vitamin A (100,000 IU) or placebo when immunised with standard-titre Schwarz measles vaccine. 82% of infants seroconverted to measles. In a multiple logistic regression model adjusting for maternal antibody titres, vitamin A supplementation was associated with a lower likelihood of seroconversion to measles (odds ratio 0.40, 95% CI 0.19-0.88), and girls were less likely to seroconvert than boys (0.34, 0.15-0.76). Immunisation with standard-titre Schwarz vaccine at six months of age in this study population is characterised by high seroconversion rates. However, simultaneous high-dose vitamin A may interfere with seroconversion to live measles vaccine in infants with maternal antibody.

Antibodies, Viral↗

Mutation of nucleotide 1,762 in the core promoter region during hepatitis B e seroconversion and its relation to liver damage in hepatitis B e antigen carriers.

In chronic hepatitis B virus (HBV) infection, mutations develop frequently at nucleotides 1,762/1,764 in the X protein open reading frame, where the core promoter is also located. By using a modified allele-specific polymerase chain reaction method, the longitudinal emergence of the A-->T mutation at nucleotide 1,762 was studied in relation to precore mutations, genotype, and liver damage. First, samples from 38 carriers that were drawn before and after hepatitis B e (HBe) seroconversion were tested. T-1,762 mutant strains increased during HBe seroconversion (P = 0.004). In the HBe antigen-negative (HBeAg-) phase, T-1,762 mutants were found in 71% (12 of 17) of patients without compared with 33% (6 of 18) of patients with a concomitant precore mutation that prevents HBeAg synthesis (P = 0.08). Second, in 55 HBeAg+ patients, the T-1,762 mutant was found to be associated with more liver inflammation (P = 0.04) and fibrosis (P = 0.02), as measured by histology activity index (HAI) scores. The results show that the nucleotide (nt) 1,762 A-->T mutation often develops during HBe seroconversion, particularly in strains without precore mutations that prevent HBeAg production. For unknown reasons, the T-1,762 mutant was rare in genotype B strains. The presence of a T-1,762 mutant in the HBeAg+ phase may be useful for identifying immunoactivation in previously immunotolerant carriers, which could be valuable for selecting patients for interferon therapy.

Carrier State↗

Regression models for time to seroconversion following experimental bovine leukaemia virus infection.

This paper develops a parametric model for time to seroconversion after experimental bovine leukaemia virus (BLV) infection, and examines the effects of inoculation route, volume of inoculum, type of inoculation material, and antigen status of donor on seroconversion time. We used parametric and nonparametric statistical methodology to analyse interval data on 150 animals from 13 published reports. The log-logistic model fitted the observed times to seroconversion better than the log-normal or Weibull models, which were the considered alternatives.

Animals↗

A method to test for a recent increase in HIV-1 seroconversion incidence: results from the Multicenter AIDS Cohort Study (MACS).

We have formulated the problem of determining whether there has been an upturn in HIV-1 seroconversion incidence over the first five years of follow-up in the Multicenter AIDS Cohort Study (MACS) as that of locating the minimum of a quadratic regression or examination of two-knot piecewise spline models. Under a quadratic model, we propose a method to obtain a direct estimate and a bootstrap estimate for the location of the temporal turning point (local minimum) for HIV-1 seroconversion incidence and three methods to estimate confidence intervals for the location of the turning point for HIV seroconversion incidence: (1) Wald confidence interval estimate with or without log transformation assuming the asymptotic normality and applying the Delta method; (2) asymmetric confidence intervals using Fieller's Theorem and its modification; and (3) bootstrapping confidence intervals. Inferences for the temporal turning point based on Wald tests for a single regression term in a non-linear regression model were not reliable compared to inferences based on confidence intervals placed on calendar time. We present results using these different methods applied to the MACS data and we obtain power estimates to illustrate the performances of different methods.

Cohort Studies↗

Long-term effects of alpha-interferon for treatment of chronic hepatitis C in terms of histological changes with aminotransferase normalization and hepatitis C virus RNA seroconversion.

To assess the effects of interferon treatment on chronic hepatitis C, histological changes long after treatment were compared with normalization of aminotransferases and seroconversion of hepatitis C virus RNA. Twenty one histologically proven chronic hepatitis C patients received alpha-interferon, 3 million units 3 times weekly for 12 months. Hepatitis C virus RNA was detected by reverse transcription/polymerase chain reaction method. Follow-up liver biopsies were performed 3 to 5 years after treatment. Fourteen of 21 (67%) patients showed normal aminotransferases for 3 to 5 years after treatment. HCV RNA seroconversion was observed in 12 of these patients. These responders showed improvement in histological activity indices and in histological findings. Two patients improved from chronic active hepatitis 2a to nonspecific changes, 1 from chronic active hepatitis 2a to portal fibrosis, 1 from chronic active hepatitis 2a to chronic persistent hepatitis and 1 from chronic active hepatitis 2b to chronic persistent hepatitis. Histological improvement of the liver correlated well with normalization of aminotransferases and seroconversion of hepatitis C virus RNA. These data indicate that complete histological resolution of chronic hepatitis C can be achieved by elimination of the virus with interferon treatment.

Alanine Transaminase↗

Determinants of survival following HIV-1 seroconversion after the introduction of HAART.

BACKGROUND: Highly active antiretroviral therapy (HAART) was introduced in 1997. We aimed to assess the continuing effect of this treatment on survival and progression to AIDS after HIV-1 seroconversion. METHODS: We used Cox models to estimate the effect of calendar year on time to AIDS and death in 22 cohorts of people from Europe, Australia, and Canada who had seroconverted. Retrospective and prospective data were used. We compared the effects of age at seroconversion, exposure category, sex, and presentation during acute HIV-1 infection pre-1997 (pre-HAART), in 1997-98 (limited use of HAART), and 1999-2001 (widespread use of HAART). FINDINGS: Of 7740 seroconverters, 2000 (26%) had died. Compared with pre-1997 data, the hazard ratio (HR) for death fell sharply to 0.47 [95% CI 0.39-0.56] in 1997, dropping further to 0.16 [0.12-0.22] in 2001. Correspondingly, the proportion of person-time on HAART increased from 22% in 1997 to 57% in 2001. By contrast with the pre-HAART era, injecting drug users had significantly higher mortality in 1999-2001 than did men infected through sex with men (HR 4.28 [2.86-6.41]). However, whereas pre-1997 the risk of AIDS was higher in those aged 45 years or older at seroconversion than in people who were 16-24 years (2.03 [1.67-2.47]), in 1999-2001 there was little evidence of a difference in risk by age (HR=1.17 [0.60-2.30]; interaction p=0.06). No such attenuation in the effect of age on survival was observed (p=0.63). INTERPRETATION: Predicted survival for people with HIV-1 has continued to increase, since the introduction of HAART; however, the importance of age and exposure category as determinants of progression seems to have changed.

Acquired Immunodeficiency Syndrome↗

HBsAg subtypes among HBsAg carriers in Okinawa, Japan. Evidence of an important relationship in seroconversion from HBeAg to anti-HBe.

In Okinawa, Japan 1261 hepatitis B surface antigen (HBsAg) carriers were investigated for clinical differences among HBsAg subtypes. Among the 854 for whom they could be determined, subtype adw was found in 604 (70.7%), adr in 232 (27.2%) and others in 18 (2.1%). The overall prevalence of hepatitis B e antigen (HBeAg) was significantly lower in subtype adw (11.9%) than in adr (17.7%) (P < 0.01). The mean age of HBeAg-positive carriers was significantly lower in adw (20.4 years) than in adr (26.9 years) (P < 0.05). Seroconversion from HBeAg to antibody to HBeAg (anti-HBe) occurred in 43 carriers. The seroconversion rate was higher in adw (43.1%) than in adr (29.3%) and the seroconversion age was younger in adw (22.7 years) than in adr (27.9 years). These results suggest that carriers with subtype adw tend to seroconvert from HBeAg to anti-HBe at a higher rate and a younger age than do those with adr. HBsAg subtypes may be closely associated with the HBeAg/anti-HBe status.

Adolescent↗

The decline in CD4+ T lymphocytes as a function of the duration of HIV infection, age at seroconversion, and viral load.

BACKGROUND: The rate of CD4+ T-lymphocyte decline seen in HIV-infected patients is very variable. Although older patients, a longer duration of HIV infection, and a high level of plasma viraemia, have been associated with a faster fall in CD4+ T-cells, the relationship between these variables is still not well known. PATIENTS AND METHODS: In a cross-sectional study that included a total of 107 patients of known age and date at HIV seroconversion, the current CD4+ T-cell count and plasma viraemia were examined. Patients were not taking antiretroviral drugs, nor had received immunizations nor were suffering any intercurrent infections at the time of the study. RESULTS: The mean duration of HIV infection was 8.6+/-2.9 years. The mean CD4+ T-lymphocyte count was 367+/-264 x 10(6)/l. Mean plasma viraemia was 4.3+/-0.9 logs. In a linear regression model, the current CD4+ T-cell count was explained in 21.7% by the duration of HIV infection, while the level of plasma viraemia justified separately up to 37.0%. When both parameters were combined, they explained 58.8%. of the CD4+ lymphocyte values. In this model, a variation of one logarithm in the plasma viraemia had six times greater effect on the number of CD4+ lymphocytes than each year of HIV infection. When the age at seroconversion was added to the model, the CD4+ cell count allowed the explanation of up to 62.2% of cases. CONCLUSIONS: The age at seroconversion, the duration of HIV infection, and the level of plasma viraemia independently and substantially influence the current CD4+ lymphocyte count in HIV-infected subjects. However, other variables should exist (e.g. virus syncytium-inducing phenotype, host immunogenetic repertoire, etc.), contributing to explaining the different rate of CD4+ T-cell decline seen in HIV-infected subjects.

Adult↗

No simple association between time elapsed from seroconversion until slaughter and the extent of lung lesions in Danish swine.

The association between the extent of pathological lung lesions at slaughter and the time elapsed from seroconversion to slaughter was examined in a longitudinal study including 830 pigs from eight herds. Pigs from an age of 3 weeks were bled every fourth week, and the sera were analyzed for the presence of antibodies to Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae serotypes 2, 5, 6, 7 and 12. At slaughter, the extent of mycoplasma-like catharral pneumonia, chronic pleuritis (dorso-caudal and ventro-cranial), interlobular-scar retractions, acute pleuropneumonia and chronic pleuropneumonia was recorded.Poisson regression was used to model the relationship between time elapsed from seroconversion to slaughter (divided into 4-week intervals) and extent of lesions, including "age at slaughter" and "gender" as independent variables and "litter" as an explanatory random variable. Analysis was only performed on lesions which had a prevalence >20% in at least five of the herds (mycoplasma-like catharral pneumonia, ventro-cranial and dorso-caudal pleuritis). Only a few consistent statistical associations were revealed across herds. Pigs seroconverting to M. hyopneumoniae close to slaughter expressed the largest extent of mycoplasma-like catharral pneumonia, and early seroconversion to M. hyopneumoniae was related to large ventro-cranial pleuritic lesions. In these eight herds, recording of the extent of pathological lung lesions at slaughter at most yielded insight into the within-herd epidemiologic dynamics of M. hyopneumoniae -- and not to any of the serotypes of A. pleuropneumoniae.

Abattoirs↗

Durability of lamivudine-induced HBeAg seroconversion for chronic hepatitis B patients with acute exacerbation.

BACKGROUND/AIMS: Lamivudine-induced hepatitis B e antigen (HBeAg) seroconversion in patients with chronic hepatitis B was reported to be durable by several studies but controversy still exists. The aim of this study was to evaluate the durability of the responses of lamivudine treatment. METHODS: Among 53 chronic hepatitis B patients who had acute exacerbation and had finished lamivudine therapy after at least 6 months of treatment, 31 patients achieved full HBeAg seroconversion twice at least 1 month apart, and subsequently stopped lamivudine therapy. Post-treatment monitoring was continued for up to 87 weeks. Alanine transaminase (ALT), HBeAg and hepatitis B virus (HBV) DNA were used as indicators for relapse. RESULTS: The cumulative relapse rates at 48 and 72 weeks post-treatment were 45.4% and 56.3%, respectively. During follow up, normal ALT levels precluded relapse while ALT levels over two times the upper limit of normal indicated relapse, which correlated well with HBeAg or HBV DNA reappearance. Patients older than 25 years were more likely to experience post-treatment relapse. CONCLUSIONS: Lamivudine-induced full HBeAg seroconversion was not durable in the Taiwanese population. ALT levels were useful for relapse detection. Age was the only independent predictive factor for relapse.

Acute Disease↗

Precore stop codon mutant in chronic hepatitis B virus infection in children: its relation to hepatitis B e seroconversion and maternal hepatitis B surface antigen.

BACKGROUND/AIMS: The aims of this study were to investigate the significance of the precore stop codon mutant in the natural course of hepatitis B virus infection in children, and the influence of maternal transmission. METHODS: Sequential sera from 80 hepatitis B virus carrier children both before and after e seroconversion during long-term follow-up were studied using the polymerase chain reaction-amplification created restriction site method. Direct sequencing of the precore region was performed in 89 sera from 32 of the 80 children. RESULTS: The precore stop codon mutant coexisting with wild strain was found in 10% of children initially, and later in 25% of children before e seroconversion. After e seroconversion, wild type was still present in 75% and mutant in 39% of children at the end of follow-up. The mutant alone was present in 15% of anti-HBe positive children without concomitant aminotransferase elevation. Children with earlier emergence of this mutant tended to have higher peak aminotransferase levels. This mutant emerged less frequently in children of hepatitis B virus carrier mothers (37.5%) than in those of non-carrier mothers (65%) (p<0.05). CONCLUSIONS: These observations suggest that this mutant is selected by host immune pressure, but is not an initiator in the loss of immune tolerance during childhood chronic hepatitis B virus infection.

Adolescent↗