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PubMed1992

Demonstration of hepatitis B virus DNA by polymerase chain reaction in the serum and the liver after spontaneous or therapeutically induced HBeAg to anti-HBe or HBsAg to anti-HBs seroconversion in patients with chronic hepatitis B.

The objective was to determine the proportion of patients with chronic hepatitis B in whom hepatitis B virus DNA is demonstrated by polymerase chain reaction after HBeAg to anti-HBe or HBsAg to anti-HBs spontaneous or therapeutically induced seroconversion. Polymerase chain reaction was performed on serum 6 and 12 mo after HBeAg to anti-HBe seroconversion in 12 patients and 2, 6 and 12 mo after HBsAg to anti-HBs seroconversion in 13 patients. Polymerase chain reaction was performed on liver tissue after HBeAg to anti-HBe seroconversion in five patients and after HBsAg to anti-HBs seroconversion in one patient. Serum HBV DNA was demonstrated by polymerase chain reaction in 83% of patients 6 or 12 mo after HBeAg to anti-HBe seroconversion and in 58%, 31% and 15% of patients at 2, 6 and 12 mo, respectively, after HBsAg to anti-HBs seroconversion. Liver HBV DNA was demonstrated by polymerase chain reaction in all patients tested. Our results show that (a) a reduced level of hepatitis B virus replication persists in most of the patients after HBeAg to anti-HBe seroconversion and might be predictive of reactivation, and (b) in contrast, hepatitis B virus replication progressively disappears in most of the patients after HBsAg to anti-HBs seroconversion.

Adult↗

PubMed2000

Human herpesvirus 8 infections in the Amsterdam Cohort Studies (1984-1997): analysis of seroconversions to ORF65 and ORF73.

We have shown previously that human herpesvirus 8 (HHV8) seroconversion for antibodies to the latency-associated nuclear antigen encoded by ORF73 and/or the lytic capsid antigen (vp19) encoded by ORF65 is associated with orogenital contact and is strongly linked to the development of Kaposi's sarcoma among HIV-infected individuals in the Amsterdam Cohort Studies. Here, we investigate the relationship between seroconversion to these antigens and primary HHV8 infection. Between 1984 and 1997, 215 HHV8 seroconversions to ORF73 (106 cases or 49%) and/or to ORF65 (159 cases or 74%) were recorded in the cohort of homosexual men. The HHV8 seroconversion rate among HIV-infected homosexual men (6.2 per 100 person years) was consistently higher than among HIV-uninfected men (2.6 per 100 person years). In HIV-infected but not in uninfected individuals, seroconversion to ORF73/latency-associated nuclear antigen precedes that to ORF65/vp19. Antibody levels to both ORF65- and ORF73-encoded antigens were higher in HIV-infected than in HIV-uninfected men, and among HIV-seropositives, antibody levels to ORF65/vp19 rise even higher with declining CD4 cell counts and peak with Kaposi's sarcoma development, suggesting continuing and increasing viral replication. In 10.3% of HHV8 seroconversions, transient serum viremia could be demonstrated before or at seroconversion. Together with the previously reported link between unprotected orogenital sex and HHV8 seroconversion, our observations suggest that HHV8 seroconversions result from primary infections.

Antibodies, Viral↗

PubMed1994

HIV seroconversion in intravenous drug users in San Francisco, 1985-1990.

OBJECTIVE: To examine the HIV seroconversion rate, risk factors for seroconversion, and changes in risk behavior over time in intravenous drug users (IVDU) in San Francisco, 1985-1990. DESIGN: Observational study. SETTING: All methadone maintenance and 21-day methadone detoxification programs in San Francisco. PARTICIPANTS: A total of 2351 heterosexual IVDU, of whom 681 were seronegative at first visit and seen at least twice ('repeaters'). MAIN OUTCOME MEASURES: HIV seroconversion rates, risk factors for seroconversion, and changes in behavior. RESULTS: The HIV seroconversion rate in repeaters was 1.9% per person-year (ppy) of follow-up [2.1% in women versus 1.7% in men (not significant); 4% in African Americans versus 1% in whites (P = 0.006); 3.9% ppy in the first third of the study, 1.2% in the second (P = 0.007), and 1.9% in the last (not significant)]. Risk factors for seroconversion were five or more sexual partners per year [hazard ratio (HR) = 2.6; P = 0.02], use of shooting gallery ever (HR = 2.9; P = 0.02), and less than 1 year (lifetime) in methadone maintenance (HR = 2.7; P = 0.02). Self-reported intravenous cocaine use fell from 33 to 15% over 5 years, shooting gallery use fell from 19 to 6%, and the proportion with five or more sexual partners fell from 25 to 10%. Bleach use rose to 75% of needle-sharers. CONCLUSIONS: The 1985-1990 HIV seroconversion rate in IVDU (1.9% ppy) was comparable to that in San Francisco cohorts of homosexual men (1.4% ppy). A decline in HIV seroconversion coincided with changes in risk behavior. Stable attendance of methadone maintenance was highly protective: the seroconversion rate in subjects with 1 year or more in methadone was 12% ppy.

Adult↗

PubMed2000

Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea.

It has been suggested that hepatitis B e antigen (HBeAg) seroconversion after lamivudine therapy is durable in Caucasians with chronic hepatitis B (CHB). However, little is known whether it is also durable in endemic areas of hepatitis B virus (HBV) infection. We evaluated the posttreatment durability of lamivudine-induced HBeAg seroconversion and the predictive factors for relapse in Korean patients with CHB. We retrospectively analyzed 98 HBeAg-positive patients with CHB who were treated with lamivudine between August 1996 and December 1997. Lamivudine was given at a dose of 150 mg per day. After HBeAg seroconversion, lamivudine was continued for an additional 2 to 4 months, and posttreatment monitoring continued for up to 24 months. HBeAg seroconversion was achieved in 34 of the 98 patients (34.7%). The mean duration of treatment in these seroconverters was 9.3 +/- 3.0 months. During the follow-up period, the cumulative relapse rates at 1 year and 2 years posttreatment were 37.5% and 49.2%, respectively. Most relapses were accompanied by elevation of serum alanine transaminase (94%) and reappearance of HBeAg (81%). Pretreatment serum HBV DNA levels and the duration of additional lamivudine therapy after HBeAg seroconversion were 2 independent predictive factors for posttreatment relapse. In conclusion, lamivudine-induced HBeAg seroconversion was not durable in this endemic area. And the duration of additional lamivudine therapy after HBeAg seroconversion significantly affected the posttreatment relapse. Further studies are needed to determine the duration of lamivudine and to elucidate the cause of high relapse after HBeAg seroconversion in endemic areas of HBV.

Adult↗

PubMed1994

High rate of HIV seroconversion among patients attending urban sexually transmitted disease clinics.

OBJECTIVE: To study rates of documented HIV seroconversion and syphilis as a cofactor for seroconversion in sexually transmitted disease (STD) clinics. In the main clinic the HIV seroprevalence rate was 12% and most infections had been shown to be acquired by heterosexual contact. METHODS: We analyzed computer records of patients who had at least two HIV-antibody tests between 1 December 1987 and 31 December 1990, at STD clinics in Dade County (Miami), Florida. RESULTS: Of 5164 individuals with two HIV tests, 208 (4.0%) seroconverted. The overall seroconversion rate was 3.1 per 100 person-years. Among blacks, who accounted for 77% of seroconversions, the rate was higher for women (4.8) than for men (2.7). The highest rate was in 15-19-year-old black women (7.1 per 100 person-years). The HIV seroconversion rate was 12.8 for patients with primary or secondary syphilis diagnosed between two HIV tests, 3.1 for patients who acquired syphilis before their first HIV test, and 2.3 for patients who had never had syphilis. Eighteen per cent of all HIV seroconversions were attributable to syphilis acquired in the interval between two HIV tests. CONCLUSIONS: We found high HIV seroconversion rates, especially among black teenagers and black women, in an STD clinic population in which the majority of HIV infections were shown previously to have been acquired heterosexually. Syphilis was a marker for HIV seroconversion and syphilitic ulcers may facilitate HIV transmission. Innovative prevention programs directed towards women and adolescents should be developed and evaluated.

Adolescent↗

PubMed1999

Low levels of hepatitis C virus RNA in serum, plasma, and peripheral blood mononuclear cells of injecting drug users during long antibody-undetectable periods before seroconversion.

Screening of antibodies to hepatitis C virus (HCV) is widely used for monitoring the prevalence of HCV infections and to assess HCV infectivity. Among HCV-infected individuals in the general population, the interval between the detection of HCV RNA and the development of HCV antibodies is usually 5 to 6 weeks, but in rare cases, seroconversion may be prolonged up to 6 to 9 months. In this study, we tested for the presence of HCV RNA during the antibody-undetectable period of 19 drug-injecting HCV seroconverters to gain insight into the antibody-negative carrier status in this population. HCV seroconversion status was determined by testing the first and last serum samples obtained from each subject, using third-generation antibody screening and confirmation assays. Serial samples were tested for HCV-specific antibodies to establish the moment of seroconversion and HCV RNA by single reverse transcriptase-polymerase chain reaction (RT-PCR) and branched DNA assay (bDNA) in serum. Plasma and peripheral blood mononuclear cells (PBMCs) were independently collected and tested for HCV RNA. HCV RNA-positivity was confirmed by Southern blot hybridization and sequencing of serial samples. The 19 HCV seroconverters had a mean follow-up of 5 years (range, 1 to 8 years). Of the 19, 4 were human immunodeficiency virus (HIV)-infected before HCV seroconversion. HCV RNA was detected in serum before seroconversion in 12 (63.2%) of the 19 HCV seroconverters, independent of HIV status. In 7 of these 12, the antibody-undetectable period was relatively short (2 to 10 months). The other 5, who were all HIV-negative before HCV seroconversion, had intermittent low levels of HCV RNA before seroconversion for a period of more than 12 months, with a mean of 40.8 months (range, 13 to 94 months). In all 5 individuals, independent repeats of the experiments confirmed the presence of HCV RNA in serum, and in 3 of these individuals, HCV-positivity was confirmed in independently collected plasma and PBMC samples. Low levels of HCV RNA may be present during prolonged antibody-undetectable periods before seroconversion in a number of injecting drug users. Independent of HIV status, their immune system appears to be unable to respond to these low HCV RNA levels and was sometimes only activated after reinfections with distinct HCV genotypes. These results indicate that primary HCV infection may not always elicit the rapid emergence of HCV antibodies and suggests that persistent low levels of HCV RNA (regardless of the genotype) may not elicit at all or delay antibody responses for prolonged periods of time.

Adult↗

PubMed1992

Risk factors associated with the incidence of seroconversion to caprine arthritis-encephalitis virus in goats on California dairies.

Incidence of seroconversion to caprine arthritis-encephalitis virus (CAEV) was determined for 1,194 goats on 11 dairies, using 2 repeated annual herd tests for CAEV. Current life table methods were used to compare age-specific incidence of seroconversion for pasteurized milk-raised and unpasteurized milk-raised goats. Logistic regression models were used to determine the risk factors associated with CAEV seroconversion, and to estimate odds ratios for seroconversion for various factor levels. Goats raised by unpasteurized milk-feeding methods were 2.5 to 6.7 times more likely to seroconvert than were goats raised by pasteurized milk-feeding methods, depending on the method of comparison. Similarly, 61.6 to 85.0% of seroconversions in yearling goats possibly were attributable to unpasteurized milk feeding. Among yearling goats, CAEV seroconversion was associated with feeding method, breed, and source of goat (herd of origin) when the effect of dairy was considered. In addition to the 6.7 times greater risk of seroconversion for unpasteurized milk-raised goats, yearling goats of the Saanen and Toggenburg breeds were 2.2 and 3.3 times, respectively, more likely to seroconvert than were Alpine yearling goats. Yearling goats purchased from another source were less likely to seroconvert than were yearlings raised on the dairy where they were studied. Among goats > 1 year old, age was associated with risk of seroconversion. Goats that were 3 years old or were > or = 4 years old were 1.7 and 3.2 times, respectively, more likely to seroconvert than were 2-year-old goats, when adjusted for effect of dairy. The effects of dairy were significant (P < or = 0.001) in yearling and older goats.

Age Factors↗

PubMed1994

Immunologic marker paths for seroconversion: single determinations of immunoglobulin A and beta 2-microglobulin are not adequate to estimate time of HIV infection. Multicohort Analysis Project Workshop. Part II.

OBJECTIVE: To investigate the usefulness of single determinations of serum immunoglobulin (Ig) A and beta 2-microglobulin (beta 2M) levels in estimating the time from HIV seroconversion. SUBJECTS: Five cohorts were represented in the workshop. The Multicohort Analysis Project (MAP) workshop database comprised 1744 HIV-infected patients with documented HIV seroconversion times, 363 of whom had AIDS. Overall, 1430 patients had two or more pre-AIDS CD4+ cell counts (13056 counts); 896 patients had two or more pre-AIDS IgA measurements (6081 observations); but only 2964 beta 2M measurements were available. MAIN OUTCOME MEASURES: Marker paths for loge IgA and loge beta 2M and for square root of CD4+ cell count. Dependence on cofactors (age, sex, mode of HIV transmission) and attention to inter-individual variation in seroconversion level and annual decline in square root of CD4+ cell count. Logistic discrimination was performed using cofactor-adjusted paired loge IgA and loge beta 2M to date HIV infections as recent (within 3 years of seroconversion), intermediate, or distant (> or = 6 years after seroconversion). Transition intensities between immunologically defined states (using IgA or beta 2M) and to clinical AIDS. RESULTS: Linear functional form described the decline in square root of CD4+ cell count, except for the Italian cohort where a steeper annual loss of square root of CD4+ cell count occurred in the first year than thereafter. Square root of CD4+ cell count at seroconversion depended on age and mode of transmission. Annual loss of square root of CD4+ cell count was less severe in those infected by sexual transmission. Non-monotone functional form emerged for loge IgA with an initial decrease in the first year after seroconversion followed by an increase thereafter. Loge IgA levels were higher in older subjects and in those infected by sexual transmission, but lower in women. A quadratic growth curve described the marker path for loge beta 2M, which increased for 5-6 years after seroconversion but declined thereafter. Loge beta 2M values were significantly higher in older patients and injecting drug users, but lower in women. The considerable heterogeneity of marker paths between individuals affected all three markers, but marker values appeared to track within an individual. Discrimination based on paired IgA and beta 2M measurements from single blood samples performed poorly in classifying HIV infections as recent, intermediate or distant. High intensities of backward as well as forward transitions between immunologically defined states explained the poor discrimination based on single sample per individual. CONCLUSIONS: Further study of how serum IgA reflects HIV infection and careful clinical and statistical assessment of reduced beta 2M from 5 or 6 years after HIV infection are needed. The dependence of marker paths on mode of HIV transmission suggests that sexual transmission may have implications for HIV disease progression. The feasibility of using serum IgA and beta 2M, evaluable in single stored blood samples, to estimate time of HIV infection has been set back by our results.

Adult↗

PubMed1993

Prevalence of HBeAg and HBsAg seroconversion in patients with chronic hepatitis B.

In 37 patients with chronic hepatitis B in the stage of active viral replication the authors tried to assess the time of seroconversion of HBeAg to anti-HBe and HBsAg to anti-HBs (21 men, 13 women and 3 boys, mean age of adults 44 years). During the 8-years investigation period seroconversion of HBeAg occurred in 19 of 37 patients (51.3%) which is an annual rate of seroconversion 6.4%. HBeAg disappeared from serum after a mean period of 82 months (range 29-228 months). After seroconversion of HBeAg the ALT and AST activity declined significantly. Acute exacerbation of hepatitis before seroconversion of HBeAg was recorded in 13 of 37 patients (35%). The mean ALT activity at the peak of exacerbation was 7.93 mu kat/l, the average duration of exacerbation was 9.8 months. Seroconversion of HBsAg occurred in 7 of 37 patients (19%). The mean annual rate of seroconversion of HBsAg was 2.4% after an average period of 98 months. During the investigation period 7 patients died (19%), four of them had a constantly positive HBeAg. The authors conclude that very low annual average seroconversion of HBeAg (6.4%) and HBsAg (2.4%) in patients with chronic hepatitis B is probably caused by previous glucocorticoid treatment.

Adult↗

PubMed2000

On the inclusion of prevalent cases in HIV/AIDS natural history studies through a marker-based estimate of time since seroconversion.

In most cohort studies of HIV infection and AIDS, seroprevalent cases provide a substantial amount of information. Inclusion of these people in natural history studies requires a fairly unbiased method to estimate their seroconversion distribution. When a cohort-based estimate is not feasible, an alternative is to estimate individual seroconversion distributions, based on marker values at entry. In this paper, a non-parametric marker-based estimation method is developed. The method is applied to data from the Amsterdam cohort study on homosexual men. For seroprevalent cases who entered the study between October 1984 and April 1985, individual seroconversion distributions are estimated based on their first measured CD4 count. In subsequent survival analyses, dates of seroconversion are estimated via conditional mean imputation. Inclusion of these seroprevalent cases greatly improves the quality of the data. Age at seroconversion is a significant cofactor for disease progression, a result not found when analysis is restricted to those who seroconvert. To incorporate the uncertainty in the imputed date of seroconversion, a bootstrap procedure is developed for the computation of p-values and confidence intervals. In our analyses, standard procedures, which ignore the uncertainty in the imputed date of seroconversion, perform almost as well.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B. Asian Hepatitis Lamivudine Trial Group.

In the reported Asian lamivudine trial, the rate of hepatitis B e antigen (HBeAg) seroconversion, defined as HBeAg/hepatitis B virus (HBV) DNA seroclearance and development of anti-HBe, during 52 weeks of treatment was only 13% to 16%. To evaluate whether any factors influenced HBeAg seroconversion, data from 345 patients in that trial were reanalyzed to correlate HBeAg seroconversion with variables including treatment, age, gender, body build, histology, baseline HBV-DNA levels, and alanine transaminase (ALT) levels. Exploratory analysis using stepwise modeling revealed that HBeAg seroconversion correlated highly with pretherapy ALT (P <.001) followed by lamivudine therapy (P =.013), but only marginally with baseline HBV-DNA (P =.071) and cirrhosis (P =.066) for lamivudine 100 mg and placebo comparison. Among these four variables, only pretherapy ALT still had a highly significant (P <.001) correlation and lamivudine therapy had a borderline association (P =.066) for lamivudine 25 mg and placebo comparison. Categorical analysis revealed that HBeAg seroconversion occurred earlier and the cumulative rate was significantly higher in patients with pretherapy ALT values over 2 times the upper limit of normal (ULN) as compared with treated patients with lower ALT levels or untreated control patients with the same ALT levels (P <.001, respectively). The highest HBeAg seroconversion rate was observed in 100 mg lamivudine-treated patients with ALT levels greater than 5 times the ULN (64%) compared with patients with ALT 2 to 5 times the ULN (26%, P =.03); and ALT less than 2 times the ULN, (5%, P <.001). These results suggest that pretherapy ALT is the strongest determinant for HBeAg seroconversion during lamivudine therapy, and should be considered in selecting patients for treatment.

Alanine Transaminase↗

PubMedDate not supplied

The effect of covariates on the induction time of AIDS using improved imputation of exact seroconversion times.

This paper explores the effects of covariates such as age, gender, chronological time of seroconversion, and mode of virus transmission on the interval between HIV seroconversion and the development of AIDS. For many cohorts which are available to provide information about such effects, both the time of seroconversion and the time of onset of AIDS may be right- or interval-censored. To analyse these doubly-censored data, we propose a method in which we first estimate the marginal distribution of the chronological time of seroconversion and use this distribution to impute the seroconversion time for each subject. Subsequently, we estimate the distribution of induction times conditional on the seroconversion distribution. We apply this technique to a cohort of HIV seropositive subjects recruited from various outpatient facilities throughout Italy and show that age at seroconversion has the greatest effect on induction time.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Seroconversion following killed polio vaccine in neonates.

The study was carried out to evaluate the efficacy of IPV in neonates and to study the additive effect of IPV or OPV at birth on seroconversion with three subsequent doses of OPV. Addition of IPV or OPV at birth to the conventional OPV schedule resulted in significantly higher seroconversion rates than in the controls, who received three doses of OPV. Three doses of IPV beginning from birth resulted in significantly better seroconversion rates than in the control group. Children receiving 3 doses of IPV showed significantly greater seroconversion rates against type III polio virus than those receiving IPV/OPV at birth followed by 3 doses of OPV. The difference in the seroconversion rates against the other virus types was not significant. A significantly greater number of children who received some vaccine at birth (IPV or OPV) were protected against poliomyelitis by 6 weeks age as compared to those who received no immunization at birth. The study recommends that seroconversion rates following three doses of IPV are satisfactory. Addition of IPV or OPV at birth to the conventional schedule markedly increases the seroconversion rates. Immunization can be started at birth to ensure early protection against poliomyelitis.

Antibodies, Viral↗

PubMed2001

Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy.

A study in Chinese patients with chronic hepatitis B showed that treatment with lamivudine for 1 year significantly improves liver histology and enhances hepatitis B e antigen (HBeAg) seroconversion compared with placebo. Fifty-eight patients from this 1-year study have received long-term treatment with lamivudine 100 mg; the outcome of 3 years of lamivudine is reported here. Before treatment, all patients had detectable HBeAg. HBeAg seroconversion (HBeAg-negative, anti-HBe-positive), hepatitis B virus (HBV)-DNA suppression, alanine transaminase (ALT) normalization, emergence of YMDD variant HBV, liver histology, and long-term safety were assessed. After 3 years of continuous treatment with lamivudine 100 mg daily, 40% (23 of 58) of patients achieved HBeAg seroconversion. In patients with baseline serum ALT >2 x upper limit of normal (ULN), the rate of HBeAg seroconversion was 65% (17 of 26). Median serum HBV-DNA concentrations were below the level of detection, and median ALT concentrations were within the normal range throughout 3 years of treatment. YMDD variant HBV emerged in 33 of 58 (57%) patients during the 3 years, of whom 9 (27%) achieved HBeAg seroconversion (6 after emergence of YMDD variant HBV). ALT levels and histologic scores after emergence of YMDD variant HBV did not show major deterioration. Lamivudine was well tolerated during 3 years of therapy. In conclusion, these data in Chinese patients with chronic hepatitis B show enhanced seroconversion rates with extended lamivudine treatment. Up to two thirds of patients with moderately elevated pretreatment ALT achieved HBeAg seroconversion after 3 years of therapy.

Adolescent↗

PubMed2002

Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B.

During the course of chronic hepatitis B virus (HBV) infection, hepatitis B e antigen (HBeAg) seroconversion to its antibody (anti-HBe) often coincides with normalization of liver biochemical test and clinical remission, but data regarding long-term outcome after spontaneous seroconversion are still scarce. Excluding patients with other virus(es) concurrent infection, 283 patients with chronic HBV infection were followed up for at least 1 year after spontaneous HBeAg seroconversion to anti-HBe. Follow-up studies included clinical, biochemical, and virologic evaluation and hepatocellular carcinoma (HCC) screening with ultrasonography and alpha-fetoprotein assay. During a median follow-up period of 8.6 years (range, 1 to 18.4 years) after HBeAg seroconversion in 283 patients, 189 (66.8%) showed sustained remission, whereas the remaining 94 (33.2%) experienced alanine aminotransferase (ALT) elevation over twice the upper limit of normal: 12 (4.2%) associated with HBeAg reversion, 68 (24%) with detectable serum HBV DNA but HBeAg negative, and 14 (4.9%) of undetermined causes. Of the 269 patients without evidence of cirrhosis at the time of HBeAg seroconversion, 21 (7.8%) developed cirrhosis with a cumulative incidence and relative risk significantly higher in patients developing active hepatitis than in patients with sustained remission (P <.05). HCC developed in 6 (2.2%) of the 283 patients, also with a significantly higher cumulative incidence in patients developing active hepatitis after HBeAg seroconversion (P <.005). In conclusion, the results suggest that spontaneous HBeAg seroconversion confers favorable long-term outcomes. However, active hepatitis still may develop and lead to cirrhosis and HCC.

Adolescent↗

PubMed1993

Differences in risk factors for human immunodeficiency virus type 1 seroconversion among male and female intravenous drug users.

To examine sex-specific risk factors for human immunodeficiency virus (HIV) type 1 seroconversion among intravenous drug users, the authors conducted a nested case-control study in Baltimore, Maryland, from 1988 to 1992 comparing 146 seroconverters and 539 HIV seronegative controls. Controls were matched on sex, race, date of study entry, and duration of follow-up. Risk factor data were obtained from interviews conducted at the first seroconversion visit for the case and the closest visit for the corresponding seronegative control. Since test results were not available until several weeks after interview, both interviewers and participants were unaware of seroconversion status at the time of interview. When data were analyzed using conditional logistic regression techniques, the variables which were significantly associated with seroconversion among male intravenous drug users included age less than 35 years, a sexually transmitted disease within the past 6 months, lifetime history of syphilis, and current intravenous drug use with an abscess at the injection site. Among women, only a history of three or more sex partners was positively associated with seroconversion and having a biological child under age 18 years was inversely associated with HIV seroconversion. Although the small sample size may have limited the ability to ascertain differences in risks of seroconversion among males and females, these data suggest that sexual transmission contributes to HIV infection among intravenous drug users, especially women.

Adult↗

PubMed1996

Longitudinal serum HIV RNA quantification: correlation to viral phenotype at seroconversion and clinical outcome.

OBJECTIVE: To investigate the longitudinal changes in serum HIV RNA, and to clarify whether the viral load early in infection has a predictive value for the clinical outcome; also, to correlate viral phenotype at seroconversion and changes in CD4 cell counts with viral burden. DESIGN: Twenty seroconverters with HIV isolates available at seroconversion had HIV RNA quantified by polymerase chain reaction (PCR) at seroconversion and thereafter every 6 months. Mean follow-up time was 65 months. Patients were classified according to viral phenotype at seroconversion, time to AIDS progression, serum viral load within the first year (less or more than 1.5 x 10(4) copies/ml). RESULTS: High viral load at seroconversion was followed by a significant decline within the first months (P < 0.0005). Decline to < 1.5 x 10(4) copies/ml was correlated with slower progression to AIDS (P < 0.05). A correlation between the rate of CD4 decline and the median viral load during the ensuing viral load plateau phase was also shown (P < 0.05). Subsequent to this phase the viral burden increased. Rapid progressors had higher viral load than slow- or non-progressors; this was particularly pronounced late in infection. Harbouring syncytium-inducing (SI) virus at seroconversion was associated with faster progression to AIDS than non-SI (NSI; P < 0.005). The increased in vitro replication rate of SI over NSI was not translated into significantly higher serum HIV RNA. CONCLUSION: Serum HIV RNA is high around the time of seroconversion. A significant decline within the first months hereafter is followed by a plateau phase, which in turn is followed by an increase in HIV RNA. HIV RNA early in infection has a predictive value for the clinical outcome. The increased virulence of SI over NSI virus did not translate into significantly higher HIV RNA values.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Lack of screening test sensitivity during HIV-1 non-subtype B seroconversions.

OBJECTIVE: To evaluate the serological consequences of HIV-1 group M diversity we studied the ability of screening tests to detect anti-HIV antibodies in early seroconverters infected by different HIV subtypes. SETTING: Virology Department, Bichat-Claude Bernard Hospital, Paris, France. DESIGN AND METHODS: Symptomatic patients with serial samples and with infective strains characterized by heteroduplex mobility assay. In each case, two sera were selected. The first (pre-seroconversion sample) was the last p24 antigen-positive/Western blot-non-reactive sample. The second (seroconversion sample) was the first Western blot-reactive sample. One second-generation enzyme immunoassay (EIA; Abbott) based on anti-human immunoglobulin (Ig) G-conjugate and three third generation EIA (Abbott; Enzygnost; Genscreen) based on the double antigen sandwich principle, detecting IgM and IgG, were used. RESULTS: Ten patients had subtype B strains and nine had non-B strains (seven were A, one E and one G). The Abbott third-generation test was more sensitive than the second generation test for pre-seroconversion subtype B samples (nine versus four out of 10; P < 0.05), but not for non-B subtypes; only two of the nine non-B sera tested were positive by both EIA. Positivity rates and optical densities differed (P < 0.05) between B and non-B subtypes in all third-generation EIA. There was no significant difference between the subtype B and non-B groups with regard to the interval between the pre-seroconversion sample and the seroconversion sample (subtype B, 6.7 +/- 2.6 days; non-B, 5.2 +/- 1.7 days). No significant difference in positivity rates and optical densities were found between B and non-B subtypes in these seroconversion samples. CONCLUSION: The shorter time since HIV infection required for sera to become reactive in third-generation EIA screening tests is due to better sensitivity for subtype B strains only. These results stress the importance of strict donor selection, the need to test screening kits against large panels of all subtypes, and the place of p24 antigen testing in closing the window of seroconversion.

Antibodies, Viral↗