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Immune markers and viral load after HIV-1 seroconversion as predictors of disease progression in a cohort of haemophilic men.

OBJECTIVE: To assess the prognostic value of HIV RNA levels measured shortly after HIV seroconversion and whether markers of immune response (CD4+ and CD8+ T-cell counts, IgA and IgG) measured at the same time, continue to provide prognostic information once the HIV RNA level is known. DESIGN AND METHODS: HIV RNA levels were measured approximately 2.5 years after seroconversion in 97 haemophilic men followed for up to 17 years. Levels of CD4+ and CD8+ T cells, IgA and IgG were measured within 1 year of the HIV RNA level. The relationships between these markers and progression to AIDS and death were studied using Kaplan-Meier plots and proportional hazards regression models. RESULTS: High HIV RNA levels were associated with faster progression to AIDS and shorter survival in univariate Cox regression models. High IgA and IgG levels were also associated with faster disease progression. In multivariate models, high HIV RNA levels remained independently associated with faster disease progression [relative hazard (RH), 1.86; P = 0.01 for AIDS; RH, 1.66; P = 0.05 for death). However, high IgA and IgG levels provided strong independent prognostic information for AIDS and death (IgA: RH, 1.38; P = 0.006 for AIDS; RH, 1.33; P = 0.07 for death; IgG: RH, 1.10; P = 0.02 for AIDS; RH, 1.12; P = 0.01 for death). CONCLUSIONS: Our results confirm the importance of the HIV RNA level in assessing the long-term prognosis in individuals infected with HIV. However, our results suggest that immune activation markers, rather than merely reflecting high HIV RNA levels are important in assessing prognosis in their own right. These findings may improve our understanding of HIV pathogenesis and may aid clinical management of patients.

Biomarkers↗

Vitamin A and risk of HIV-1 seroconversion among Kenyan men with genital ulcers.

BACKGROUND: Vitamin A is involved in normal immune function and the maintenance of mucosal integrity through complex effects on cellular differentiation. OBJECTIVE: We sought to determine whether serum vitamin A levels were associated with altered susceptibility to primary infection with HIV-1 in men with high-risk sexual behaviour and genital ulcers who presented for treatment at an STD clinic in Nairobi, Kenya. METHODS: HIV-1 seronegative men were prospectively followed. Vitamin A levels at study entry were compared among 38 men who HIV-1 seroconverted versus 94 controls who remained HIV seronegative. RESULTS: Vitamin A deficiency (retinol less than 20 microg/dl) was very common and was present in 50% of HIV-1 seroconverters versus 76% of persistent seronegatives. Seroconversion was independently associated with a retinol level greater than 20 microg/dl (HR 2.43, 95% CI 1.25-4.70, P = 0.009), and a genital ulcer aetiology caused by Haemophilus ducreyi (HR 3.49, 95% CI 1.03-11.67, P = 0.04). Circumcision was independently associated with protection (HR 0.46, 95% CI 0.23-0.93, P = 0.03). CONCLUSION: Vitamin A deficiency was not associated with an increased risk of HIV-1 infection among men with concurrent STD. A decreased risk of HIV-1 seroconversion was independently associated with lower retinol levels. The effects of vitamin A on macrophage and lymphoid cell differentiation may paradoxically increase mucosal susceptibility to HIV-1 in some vulnerable individuals, such as men with genital ulcers. Lack of circumcision and chancroid are confirmed as important co-factors for heterosexual HIV-1 transmission. The role of vitamin A in heterosexual HIV-1 transmission requires further study.

Adult↗

Systemic non-Hodgkin lymphoma in individuals with known dates of HIV seroconversion: incidence and predictors.

OBJECTIVES: To investigate temporal changes in the risk of non-Hodgkin lymphoma (NHL) and estimate NHL incidence in risk groups and the prognostic role of these risks and current, nadir and time-weighted average CD4 cell count. METHODS: Secular trends in time from HIV seroconversion to an NHL diagnosis was estimated using Cox models from data pooled from the 22 seroconverter cohorts in the CASCADE collaboration for three periods (pre-1997, 1997-1998, 1999-2002), adjusting for age at seroconversion, exposure category and sex. RESULTS: Of 7103 seroconverters, 129 developed NHL. Compared with pre-1997, there was little reduction in NHL risk in 1997-1998 [relative risk (RR), 0.66; 95% confidence interval (CI), 0.37-1.17] then a substantial reduction in 1999-2002 (RR, 0.25, 95% CI, 0.12-0.53). Compared with individuals with CD4 cell count > 350 x 10 cells/l, the RR of NHL increased to 1.9 (95% CI, 1.0-3.6), 1.4 (95% CI, 0.6-3.5) and 11.2 (95% CI, 6.3-20.0) at CD4 cell counts 200-349, 100-199 and < 100 x 10 cells/l, respectively. There was no evidence that nadir (P = 0.41) or time-weighted average CD4 cell count (P = 0.38) contributed further to predicting NHL risk or were better predictors than current CD4 cell count. For individuals with CD4 cell count > 350 x 10 cells/l pre-HAART, an NHL incidence of 1.8 and 0.4/1000 person-years was estimated for those at highest and lowest risk, respectively, when classified by age and exposure category. CONCLUSION: There appears to be no justification for initiating HAART at CD4 cell counts > 100 x 10 cells/l based specifically on concerns over NHL. The risk of NHL is, however, greatly increased at lower CD4 cell counts.

Adolescent↗

Hepatitis C virus seroconversion and genotype prevalence in patients and staff on chronic hemodialysis.

The prevalence of hepatitis C virus (HCV)-RNA positivity among hemodialysis patients varies between 10 and 70%. Few previous surveys revealed high frequency of seroconversion of HCV-RNA-negative patients over the years of hemodialysis. Only few studies reported HCV genotype variability. We evaluated all 65 patients on chronic hemodialysis in our dialysis unit. All sera positive to anti-HCV on ELISA were retested by reverse transcriptase polymerase chain reaction to HCV-RNA. Sixteen patients were found anti-HCV positive on ELISA, and 8 of them were also PCR positive. Three of these eight patients seroconverted during the year 1995. Four patients had both 1a and 1b genotypes of HCV, coexistence of genotypes 1b and 4a in one patient and genotypes 1a, 1b and 2a in the remaining three patients. Mean serum aminotransferase, duration of dialysis, and number of blood units transfused were significantly higher in the HCV-PCR-positive patients compared with the HCV-PCR-negative patients. Because strict isolation methods were initiated at the end of 1995, not one new case of HCV among dialysis patients was found in 1998, although new hemodialysis patients were diagnosed as having HCV. In conclusion, genotypes 1a and 1b, as is true for the general population in Israel, were also the predominant genotypes among hemodialysis patients; the coexistence of more than one genotype is common among hemodialysis patients; seroconversion is common among these patients and strict isolation methods are efficient and should be recommended.

Antibodies, Viral↗

Acute seroconversion of HIV infection in the ambulatory care setting.

Patients frequently visit ambulatory care settings with acute human immunodeficiency virus (HIV) seroconversion illness, but the illness is often misdiagnosed. This acute viral syndrome, or seroconversion illness, occurs after initial exposure to the HIV virus; it is often resolved before the development of HIV-specific antibodies. Primary HIV infection refers to the 12 months following infection; it includes an acute time period after exposure when routine HIV antibody testing is negative. Primary HIV infection is recognized with the help of a detailed screening history. Diagnosis is confirmed through laboratory tests that detect virus presence. The accurate diagnosis of primary HIV infection can have a beneficial effect on the patient's clinical course and also on public health prevention efforts.

AIDS Serodiagnosis↗

HIV infection among foreign transsexual sex workers in Rome: prevalence, behavior patterns, and seroconversion rates.

BACKGROUND: The Azienda Sanitaria Locale Roma E (ASL-RME) outpatient clinic is the main reference center in Rome for HIV testing of foreign people. GOAL: To define the prevalence and incidence of HIV infection among foreign transsexual sex workers attending the center. STUDY DESIGN: A cross-sectional, follow-up study was conducted. RESULTS: Between 1993 and 1999, 353 transsexuals attended the ASL-RME. They were from Colombia (n = 208), Brazil (n = 122), and other countries (n = 23). Most of these transsexuals reported having 5 to 10 partners per day. The overall HIV prevalence was 38.2%, which multivariate analysis found to be associated with origin from Brazil and a higher number of sex partners. The observed HIV seroconversion rate was 4.1 per 100 person-years, and non-regular condom use was the only factor related to seroconversion. CONCLUSIONS: The data from this study suggest that promotion of safer sex practices and regular condom use still is the main priority among marginalized population subgroups, such as foreign prostitutes, involved in sex activities that put them at risk for HIV infection.

Adult↗

Reverse seroconversion of hepatitis B after allogeneic bone marrow transplantation: a retrospective study of 37 patients with pretransplant anti-HBs and anti-HBc.

BACKGROUND: Reverse seroconversion to hepatitis B virus (HBV), i.e., HBV reactivation in patients with pretransplant antibodies to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc), is rarely re-ported after allogeneic bone marrow transplantation. METHODS: To determine this risk, we studied clinical outcome and serological changes in 37 patients with pretransplant anti-HBs and anti-HBc. RESULTS: In 33 cases, no change in HBV markers was observed in the posttransplant period. In four cases, anti-HBs and anti-HBc were lost, and hepatitis B surface antigen, hepatitis B e antigen, and HBV DNA emerged together with acute hepatitis, after cessation of immunosuppression. The actuarial risk of reactivation in the 37 patients was 20.5% (median follow-up 20 months). No reactivation occurred in patients with anti-HBs-positive donors. CONCLUSION: Although few cases of postallogeneic bone marrow transplantation reverse seroconversion to HBV have been reported, this study demonstrates that the actuarial risk is relatively high and suggests that donor vaccination might be proposed prophylactically or that HBs-specific immunoglobulin infusions might be warranted.

Adolescent↗

Short-term CD4 cell response after highly active antiretroviral therapy initiated at different times from seroconversion in 1,500 seroconverters.

The effect of HIV infection duration and CD4 cell count on short-term CD4 response was evaluated in treatment-naive seroconverters using logistic regression adjusted for CD4 count before highly active antiretroviral therapy (HAART) as well as for exposure category, age, sex, acute infection, and cohort. This association was also investigated in pretreated seroconverters, further adjusting for prior therapy. CD4 response (increase of >100 cells/microL at 6 months) was more likely if HAART was initiated in the first year following seroconversion (OR = 1.50 [95% CI: 1.07-2.10] compared with 2-5 years). There was no improvement in response from initiating HAART with CD4 count >350 cells/microL compared with 201 to 350 cells/microL. Below 200 cells/microL, however, the chance of a CD4 response appeared to be reduced (OR = 0.72 [95% CI: 0.40-1.28] for 0-200 cells/microL compared with 201-350 cells/microL, P = 0.26). Results were similar for pretreated individuals. Further, in pretreated individuals, a CD4 response was less likely if the CD4 nadir was lower than the pre-HAART CD4 count (OR = 0.18 [95% CI: 0.10-0.36] for >150 cells/microL difference between nadir and pre-HAART CD4 count vs. no difference, P < 0.001). Given the limitations of observational studies, particularly the inability to control for unmeasured confounders, these findings suggest that the initiation of HAART within the first year following seroconversion appears to improve short-term immunologic response. After that time, there is little to be gained in terms of short-term response from initiating HAART before reaching a CD4 count of 200 cells/microL.

Acquired Immunodeficiency Syndrome↗

The role of HBeAg seroconversion in acute exacerbation of liver disease with termination of hepatitis B and D virus infection in a chronic hepatitis D patient during alpha-interferon therapy.

We report a severe flare-up in a chronic hepatitis patient due to dual infection with hepatitis B and D viruses during alpha-interferon therapy. Pre-treatment, the patient had detectable levels of both viruses. After 9 months of therapy, an alanine aminotransferase flare with acute hepatic decompensation was detected. Alpha-interferon was discontinued and lamivudine (100 mg once daily) was started, after which the patient reversed slowly. Hepatitis B early antigen (HBeAg) seroconversion with hepatitis B virus-DNA clearance was observed 1 month after the flare; 15 months later, the patient had persistently normal alanine aminotransferase levels with negative results for both serum hepatitis B virus-DNA and hepatitis D virus-RNA. In conclusion, liver disease may be exacerbated during interferon therapy in patients with chronic hepatitis D who are also positive for hepatitis B surface antigen (HBsAg) and HBeAg. Therefore, extra care in monitoring should be considered and strict follow-up is recommended, since clearance of hepatitis D may occur after HBeAg seroconversion in coinfected patients. Lamivudine may be administered early in hepatitis D-RNA/HBsAg-positive patients at high risk of liver failure once a severe flare-up occurs during interferon therapy.

Acute Disease↗

Predictors of repeat testing and HIV seroconversion in a sexually transmitted disease clinic population.

OBJECTIVE: This study assessed the extent of and characteristics associated with repeat HIV testing in persons presenting to a sexually transmitted disease (STD) clinic. METHODS: The study population included all 101 newly diagnosed HIV-infected subjects and 411 matched HIV-uninfected subjects identified over a 5-year period in a publicly funded STD clinic in the southeastern United States. RESULTS: Of the 508 subjects (99%) with available records, 160 (32%) had tested previously. Age, race, return for posttest counseling, and the client's stated reason for coming to the clinic were associated with repeat testing. Among the 160 subjects who had tested previously, self-identifying as a man who has sex with men or having a history of incarceration was strongly associated with HIV seroconversion (adjusted odds ratio [OR], 51.82; 95% confidence interval [CI], 9.10-295.13; adjusted OR, 83.98, 95% CI, 17.26-408.69, respectively). Presenting for STD-related reasons (STD symptoms or requesting an STD check) had a negative association with HIV seroconversion (adjusted OR, 0.07; 95% CI, 0.01-0.90) compared with presenting for the sole purpose of requesting an HIV test. CONCLUSIONS: Repeat HIV testing is common among patients receiving services at an STD clinic. The role of repeat testing in HIV prevention efforts is complex and poorly understood. Results from this study could be used to identify and target those testing previously at highest risk for contracting HIV for risk-reduction interventions.

AIDS Serodiagnosis↗

Viral load and CD4 count dynamics after HIV-1 seroconversion in homosexual and bisexual men in Rio de Janeiro, Brazil.

PURPOSE: Reliable predictors of HIV disease progression are scarce in developing countries, where most HIV infections occur. We describe early virologic and immunologic events among men who have sex with men in Rio de Janeiro, Brazil. METHODS: Seroconverters from 2 high-risk cohorts were followed for up to 36 months with periodic laboratory evaluations, plasma viral load, and CD4 count assessments. Viral load and CD4 count mean trajectories were computed. For the modeled viral loads, mean and median values were 24,480 (4.36 log10) and 19,720 (4.29 log10) copies/mL (range 14,880-58,090), respectively. Median CD4 count was 373 cells/microL (range 260-508). Overall variation on viral loads ranged from 4.3 to 5.2 log10 copies/mL with a visible increase in the viral load starting at approximately 600 days (n = 12) after estimated time of seroconversion. The initial period of HIV infection was characterized by an increase in CD4 count (n = 29) followed by a steep decline starting at approximately 200 days (508 cells, 95% CI: 425 to 569). A gradual decrease was observed in the median CD4 count thereafter, reaching 281 (95% CI: 100 to 466) at 1000 days after the estimated date of seroconversion. CONCLUSIONS: Although viral load dynamics resembled those observed in developed countries, CD4 counts seem to decline at a faster rate than in the Multicenter AIDS Cohort Study (MACS) cohort. Clinical and survival data are needed to assess the impact of interventions, such as antiretroviral therapy, on the clinical course of HIV infection in Brazil.

Adult↗

Characteristics of persons with recently acquired HIV infection: application of the serologic testing algorithm for recent HIV seroconversion in 10 US cities.

BACKGROUND: Information about the characteristics of persons whose HIV diagnosis was made soon after infection contributes to a better understanding of the HIV epidemic and to appropriate targeting of care and prevention efforts. METHODS: In 10 US cities from 1997 through 2001, specimens from consenting persons for whom a diagnosis of HIV was made within the past 12 months in were tested using the serologic testing algorithm for recent HIV seroconversion. The characteristics of those whose HIV diagnosis occurred within 170 days (on average) from seroconversion were identified. RESULTS: For 191 (20%) of the 964 participants, an HIV diagnosis was made during the period of recent infection. These diagnoses of recent infection were made more frequently among men (21.7%), whites (29.3%), men who have sex with men (25.5%), persons with a known HIV-infected partner (24.9%), and persons with a diagnosis of gonorrhea made in the 12 months before interview (27.0%). Recent infection was diagnosed less frequently among African Americans (15.5%), Latinos (15.5), and heterosexual men (14.7%) and women (14.4%). CONCLUSIONS: To increase early diagnosis of HIV, HIV testing should be more routinely offered to persons with a recent history of sexually transmitted diseases and to African Americans and Latinos in a variety of settings.

AIDS Serodiagnosis↗

Identification of human papillomavirus seroconversions.

The temporal relationship between primary genital human papillomavirus (HPV) infections and the induction of antibodies against viral antigens has not been established. In order to address this question we studied a cohort of 110 women and 48 men with multiple heterosexual partners, who were followed for 220 person-years during which they made 583 visits to the sexually transmitted diseases clinic of the Amsterdam Public Health Service. At each visit spatula or brush samples from multiple anogenital and oral sites were collected for HPV DNA analysis by PCR. Serum samples were also collected and analysed for serological reactivity to peptides derived from the L1, L2 and E2 regions of HPV types 6, 16 and 18 as well as to bovine papillomavirus and HPV-16 virus-like particles. Seroconversions for at least three antigens were found among 16/158 patients. Of these, 10/16 were HPV-positive and in 5/16 cases seroconversions occurred concomitantly with the detection of HPV DNA. Analysis of participants who were HPV-negative at entry, but became HPV DNA-positive during follow-up revealed that antibodies against several HPV antigens were regularly induced at the time of a new HPV infection, in particular the IgG responses against HPV-16 virus-like particles and against the HPV-16 E2-derived peptide 245. Whereas the responses induced among the women with new HPV-16 infection tended to continuously increase, the responses among the men with any type of new HPV infection were mostly transient and disappeared during follow-up. In conclusion, we find that antibody responses to multiple viral antigens are often induced following the detection of genital HPV infection, that the type-specificity of the response is limited and that transient responses are common.

Adolescent↗

Study of seroconversion of antibody to human T-cell lymphotropic virus type-I in children of Okinawa, Japan.

From 1983 to 1986, 1,813 children in nursery schools in Ishigaki Island and 1,228 children under 15 years old in the rural area in the Yaeyama District of Okinawa, Japan, were tested for anti-HTLV-I; 18 children (1.0%) in Ishigaki Island and 39 children (3.2%) in the rural area were positive. In order to survey when anti-HTLV-I developed in these children, their older serum samples were investigated retrospectively for 1 to 5 years. Two cases of seroconversion from anti-HTLV-I negative to positive were found between the age of 2 and 4, and there were no cases of seroconversion over 4 years old. Among the children who suffered maternal transmission of HTLV-I and developed anti-HTLV-I before the age of 15, about 80% of the children were considered to have anti-HTLV-I before the age of 2, and the remainder developed anti-HTLV-I before the age of 4.

Adolescent↗

48 weeks pegylated interferon alpha-2a is superior to 24 weeks of pegylated interferon alpha-2b in achieving hepatitis B e antigen seroconversion in chronic hepatitis B infection.

BACKGROUND/AIM: Although 48-week therapy with pegylated-interferons has been shown to be effective for the treatment of chronic hepatitis B virus infection, the efficacy of a shorter duration of therapy with pegylated interferons is unknown. METHOD: We reviewed 53 hepatitis B e antigen positive Chinese patients treated with 48 weeks of pegylated interferon alpha-2a or 24 weeks of pegylated interferon alpha-2b. Sustained virological response was defined as hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL at week 72. RESULTS: Twenty-nine patients were treated with 48 weeks of pegylated-interferon-alpha-2a and 24 patients with 24 weeks of pegylated-interferon-alpha-2b. At the end-of-therapy, hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL were similar between the two groups of patients [9/29 (31.0%) vs. 2/24 (8.3%), respectively, P = 0.09]. At week 72, 10 of the 29 patients (34.5%) treated with 48 weeks of pegylated-interferon-alpha-2a compared with two of the 24 patients (8.3%) treated with 24 weeks of pegylated-interferon-alpha-2b had sustained virological response (P = 0.04). By logistic analysis, 48 weeks of pegylated-interferon-alpha-2a was independently associated with sustained virological response (P = 0.04 adjusted hazards-ratio 9.37). CONCLUSION: Further studies are required to determine the optimal duration of therapy with pegylated interferons in chronic hepatitis B.

Adult↗

Long-term remission of recurrent parvovirus-B associated anemia in a renal transplant recipient induced by treatment with immunoglobulin and positive seroconversion.

Parvovirus B-19 (PVB)-related recurrent anemia is reported in a renal transplant recipient with long-term remission induced by intravenous immunoglobulin and decreasing immunosuppression. Positive plasma polymerase chain reaction (PCR) and intense bone marrow infection were present at diagnosis, despite the absence of serum immunoglobulin IgG and IgM antibodies to the virus. Seroconversion against the virus was followed by long-term remission while the plasma PCR for PVB remained positive. This case illustrates the absence of serum antibodies in an immunosuppressed host despite florid infection with the virus. Positive seroconversion in a naïve subject is associated with long-term remission even in the presence of detectable viral DNA copies in the plasma.

Adult↗

HIV seroconversion in Swedish haemophiliacs: relation to type and dosage of factor concentrate.

Human immunodeficiency virus (HIV) seroconversion among 40 Swedish haemophilia A patients has been investigated by retrospective sera testing. 22/40 patients had developed HIV antibodies before 1983, i.e., when heat-treatment of American factor concentrates was introduced. All patients had received American and Swedish factor concentrates, thus no case of seroconversion was seen among patients treated exclusively with non-heat-treated Swedish concentrates. Of 79 patients with severe or moderate haemophilia, all of whom had received both American and Swedish concentrates, the 36 seropositives were compared with the 43 seronegatives. The total number of units received did not differ between the two groups, though the seropositive group had received significantly more American concentrate. Two batches of concentrate were proved to have been infected. 29 seropositive and 13 seronegative patients had been treated with at least one of these batches. As expected, and unlike most of the seronegative patients, patients in the seropositive group generally had abnormal lymphocyte subsets.

Acquired Immunodeficiency Syndrome↗

Anti-HIV seroconversion: initial appearance of antibodies to core proteins and rapid raise in antibody levels. Case report.

Anti-HIV seroconversion was recorded in a patient by means of Western blot, immunofluorescence and ELISA analysis on sera taken at one to five day intervals. Seroconversion was first detected in the Western blot by antibodies to p15 and p24 and was followed by a rapid increase in levels of antibodies during the following days and weeks.

Acquired Immunodeficiency Syndrome↗