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PubMed2002

Changes over calendar time in the risk of specific first AIDS-defining events following HIV seroconversion, adjusting for competing risks.

BACKGROUND: Although studies have reported large reductions in the risks of AIDS and death since the introduction of potent anti-retroviral therapies, few have evaluated whether this has been similar for all AIDS-defining diseases. We wished to evaluate changes over time in the risk of specific AIDS-defining diseases, as first events, using data from individuals with known dates of HIV seroconversion. METHODS: Using a competing risks proportional hazards model on pooled data from 20 cohorts (CASCADE), we evaluated time from HIV seroconversion to each first AIDS-defining disease (16 groups) and to death without AIDS for four calendar periods, adjusting for exposure category, age, sex, acute infection, and stratifying by cohort. We compared results to those obtained from a cause-specific hazards model. RESULTS: Of 6,941, 2,021 (29%) developed AIDS and 437 (6%) died without AIDS. The risk of AIDS or death remained constant to 1996 then reduced; relative hazard = 0.89 (95% CI: 0.77-1.03); 0.90 (95% CI: 0.81-1.01); and 0.32 (95% CI: 0.28-0.37) for 1979-1990, 1991-1993, and 1997-2001, respectively, compared to 1994-1996. Significant risk reductions in 1997-2001 were observed in all but two AIDS-defining groups and death without AIDS in a competing risks model (with similar results from a cause-specific model). There was significant heterogeneity in the risk reduction across events; from 96% for cryptosporidiosis, to 17% for death without AIDS (P < 0.0001). CONCLUSION: These findings suggest that studies reporting a stable trend for particular AIDS diseases over the period 1979-2001 may not have accounted for the competing risks among other events or lack the power to detect smaller trends.

AIDS-Related Opportunistic Infections↗

PubMed1991

Indeterminate human immunodeficiency virus type 1 western blots: seroconversion risk, specificity of supplemental tests, and an algorithm for evaluation.

The human immunodeficiency virus type 1 (HIV-1) Western blot is indeterminate in 10%-20% of sera reactive by EIA. Eighty-nine individuals with prior repeatedly reactive EIA and indeterminate Western blots were followed prospectively to study the risk of seroconversion and specificity of supplemental tests. Four high-risk cases seroconverted within 10 months after enrollment (seroconversion risk, 4.5%, 95% confidence interval, 1.2%-11.1%). Among cases with p24 bands initially, 4 (18.2%) of 22 high-risk individuals seroconverted compared with 0 of 33 low-risk cases (P = .03). Specificities of HIV-1 culture, serum p24 antigen, polymerase chain reaction, and recombinant ENV 9 EIA were 100%, 100%, 98.6%, and 94.4%, respectively. An expedited evaluation protocol is proposed. Low-risk individuals with nonreactive EIAs upon repeat testing do not need further follow-up; high-risk individuals should be followed serologically for at least 6 months, especially those with p24 bands on Western blot.

AIDS Serodiagnosis↗

PubMed1991

Absence of chronic human immunodeficiency virus infection without seroconversion in intravenous drug users: a prospective and retrospective study.

It has been reported that human immunodeficiency virus type 1 (HIV-1) infection may exist in persons without specific antibodies for years. To measure the frequency of a silent carrier state, a study was conducted in a cohort of 124 intravenous drug users (IVDUs) without anti-HIV-1 antibodies. All the participants had engaged in high-risk behavior for HIV-1 transmission for a number of years until 1987 or later. Samples were analyzed at 6-month intervals for the presence of HIV-1 provirus using DNA amplification and for the appearance of anti-HIV-1 antibodies. HIV-1 provirus and antibodies were undetectable in 122 participants, whereas seroconversion was observed in 2. In one of these, both amplified HIV-1 pol gene segment and anti-HIV-1 antibodies were detected simultaneously, and in the other, provirus was detected 1 month before seroconversion. This study suggests that long-term HIV-1 infection without anti-HIV-1 antibodies is rare and that repeated antibody testing is sufficient to determine the HIV-1 status of a person no longer at high risk for HIV-1 infection.

Adult↗

PubMed1992

Rotavirus-specific breast milk antibody in two populations and possible correlates of interference with rhesus rotavirus vaccine seroconversion.

Milk was collected from 56 New York and 70 Venezuelan mothers participating in Rhesus rotavirus (RRV) pediatric vaccine trials. Plaque reduction neutralization antibody (PRNA) to RRV (VP7:3, VP4:RRV) and human P rotavirus (VP7:3, VP4:P) and epitope-blocking antibody to one RRV VP4 and VP7 epitope were determined. Controlling for postpartum age, more Venezuelan milk samples had detectable RRV and P PRNA, RRV VP4 epitope-blocking antibody (P less than or equal to .001), and higher RRV and P PRNA geometric mean titers (P = .01) than New York samples. Using a logistic regression model, both milk and infants' serum preimmunization RRV PRNA titers had a negative effect on seroconversion (P = .008 and .02, respectively). Only 25% (2/8) infants fed milk containing greater than or equal to 1:160 RRV PRNA seroconverted compared with 83% (5/6) fed milk containing less than 1:160 RRV PRNA (P = .1). Of milk samples containing greater than or equal to 1:160 RRV PRNA, seven (88%) of eight had greater than fourfold neutralizing activity against RRV versus P (P = .035), suggesting that VP4-specific milk antibodies may interfere with RRV seroconversion.

Antibodies, Viral↗

PubMed1994

Human immunodeficiency virus type 1 seroconversion in women with genital ulcers.

Genital ulcers are implicated as a risk factor enhancing susceptibility to human immunodeficiency virus type 1 (HIV-1) infection. A prospective study to determine the incidence of and risk factors associated with acquisition of HIV-1 in women with genital ulcers was done. HIV-1-seronegative women with genital ulcers attending a clinic for sexually transmitted diseases in Nairobi were followed to HIV-1 seroconversion over a 6-month period. Of 81 women, 10 seroconverted to HIV-1. The crude 6-month incidence of HIV-1 infection was 12%. Risk factors associated with seroconversion included cervical ectopy (rate ratio [RR], 4.9; 95% confidence interval [CI], 1.5-15.6) and pelvic inflammatory disease (RR, 6.3; 95% CI, 1.9-20.4). Thus, cervical ectopy and pelvic inflammatory disease may increase susceptibility to HIV-1 in women with genital ulcers.

Adolescent↗

PubMed1994

CD8+ lymphocyte activation at human immunodeficiency virus type 1 seroconversion: development of HLA-DR+ CD38- CD8+ cells is associated with subsequent stable CD4+ cell levels. The Multicenter AIDS Cohort Study Group.

Subsets of activated CD8+ lymphocytes defined by membrane expression of the activation antigens HLA-DR and CD38 were counted by three-color flow cytometry in homosexual men who subsequently became seropositive for human immunodeficiency virus type 1 (HIV). Profound CD8+ cell activation was seen in all subjects at seroconversion and 6 and 12 months later. The HLA-DR+ CD38+ CD8+ cell population, which has potent direct HIV cytotoxic T cell activity, was markedly elevated at seroconversion in all subjects. In some men, these levels remained elevated throughout the first year of infection. During the next 5 years, these men had stable CD4+ cell levels, whereas the others did not. Long-term survivors (seropositive for 9 years, > 800 CD4+ cells/mm3) also had elevated levels of this subset, despite few other activated CD8+ cells. Thus, selective elevation of HLA-DR+ CD38- CD8+ cells was a marker of subsequent stable HIV disease.

ADP-ribosyl Cyclase↗

PubMed1994

Neutralizing antibodies against sequential autologous human immunodeficiency virus type 1 isolates after seroconversion.

The emergence of human immunodeficiency virus type 1 (HIV-1) variants with different sensitivities to serum neutralization and biologic phenotype was studied for 2-5 years after primary HIV-1 infection in 5 subjects. In 3 subjects, the initial virus isolate from seroconversion could be neutralized by autologous serum, but isolates obtained at two subsequent times exhibited reduced sensitivity to serum neutralization, decreased replication in primary macrophages, and increased ability to induce syncytia. Two of these 3 subjects progressed to AIDS and died. Sequential virus isolates from the other 2 subjects showed variability in sensitivity to serum neutralization or biologic features. These patients remained relatively stable in clinical status. Thus, viruses isolated at seroconversion appear to be either non-syncytium-inducing, strong macrophage-tropic, serum neutralization-sensitive phenotypes with stable clinical status or to have escaped neutralization by autologous sera over time, have reduced macrophage tropism and increased syncytia formation, and be associated with disease progression.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Progression to acquired immunodeficiency syndrome is influenced by CD4 T-lymphocyte count and time since seroconversion.

Progression to acquired immunodeficiency syndrome (AIDS) among persons infected with human immunodeficiency virus (HIV) varies considerably and may be influenced by factors such as age, smoking, number of male partners per year, and CD4 T-lymphocyte count. The loss of CD4 lymphocytes is known to be the dominant factor in the progression to AIDS. However, it is unclear whether the effect of the CD4 lymphocyte count is of such importance that persons with similar CD4 cell counts who have been infected for widely different lengths of time have the same risk of AIDS. While a CD4 count is easily obtainable, the precise amount of time since HIV infection is in most circumstances difficult to assess. In the present analysis, 259 Danish and 245 American homosexual men were followed for up to 14 years from 1981 to 1995. Two hundred and one persons seroconverted during the study period, and 112 had developed AIDS before the end of follow-up. CD4 lymphocyte count was highly correlated with the risk of developing AIDS (p < 0.001), but AIDS risk was not affected significantly by either age at infection, smoking, or number of male partners per year (p > 0.20 in all cases). Controlled for CD4 lymphocyte count, time since seroconversion was significant in explaining the risk of AIDS (p = 0.018), with a lower risk being seen during the first 3 years after seroconversion but no effect thereafter. These data confirm the central importance of CD4 lymphocyte level in the progression of HIV disease to AIDS, and suggest that rapid progression within 3 years of infection may be related to factors other than CD4 cell count.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Risk factors for human herpesvirus 8 seropositivity and seroconversion in a cohort of homosexual men.

Sexual and nonsexual modes of transmission of human herpesvirus 8 (HHV8) have been suggested, but specific routes remain unclear. Therefore, the objective of this study was to assess risk factors for HHV8 seropositivity and determine specific sexual practices associated with HHV8 seroconversion. Sera from 1,458 homosexual men (Amsterdam Cohort Study, 1984-1996) were tested for antibodies to HHV8 with a modified version of an enzyme immunoassay, using recombinant HHV8 lytic phase capsid (ORF65) and latent phase nuclear (ORF73) proteins. HHV8 seroprevalence at study entry was 20.9% (305/1,458); was highest among those with positive human immunodeficiency virus (HIV) status, no steady partner, and southern European or Latin American nationality; and increased with older age and higher number of sexual partners. During follow-up, 215 men seroconverted for HHV8 (incidence: 3.6/100 person-years). Both prevalence and incidence rates remained more or less stable during the study period. Orogenital insertive sex (odds ratio (OR) = 5.95; 95% confidence interval (CI): 2.88, 12.29) or orogenital receptive sex (OR = 4.29; 95% CI: 2.11, 8.71) with more than five partners in the past 6 months, older age (OR = 2.89; 95% CI: 1.13, 7.34, when older than 45 years), and preceding HIV infection (OR = 2.47; 95% CI: 1.53, 3.99) were independent predictors for HHV8 seroconversion. The authors found strong evidence for orogenital transmission of HHV8 among homosexual men.

Adult↗

PubMed1992

The harm reduction approach and risk factors for human immunodeficiency virus (HIV) seroconversion in injecting drug users, Amsterdam.

To assess risk factors for seroconversion to human immunodeficiency virus, the authors studied a cohort of human immunodeficiency virus-seronegative injecting drug users in Amsterdam, the Netherlands, between December 1985 and November 1991. The behaviors of 31 seroconverters were compared with those of 202 seronegative injecting drug users (controls). Three independent risk factors for seroconversion were found in logistic regression: 1) living greater than 10 years in Amsterdam (odds ratio (OR) = 2.45, 95% confidence interval (CI) 1.09-5.53); 2) first injection less than or equal to 2 years ago (OR = 3.43, 95% CI 1.20-9.81); and 3) injecting mainly at home (OR = 0.39, 95% CI 0.18-0.88). No evidence was found that receiving daily methadone treatments at methadone posts and obtaining new needles/syringes via the exchange program were protective. However, the data suggest that exchanging needles may have been protective at the start of this program. Influencing injecting drug users to modify behavior to prevent new infections appears to be very difficult, and it may, therefore, be important to increase preventive efforts targeted at the sexual partners of injecting drug users.

Adult↗

PubMed1995

Evaluation of secular trends in CD4+ lymphocyte loss among human immunodeficiency virus type 1 (HIV-1)-infected men with known dates of seroconversion.

The rate at which immunodeficiency develops in untreated human immunodeficiency virus type 1(HIV-1)-infected persons might be increasing or decreasing over time because of viral evolution or other factors. Beginning in 1984, Multicenter AIDS Cohort Study investigators recruited HIV-1-seronegative homosexual/bisexual men from four US metropolitan areas and examined them semiannually for HIV-1 seroconversion. To assess possible secular changes in the natural history of HIV-1 infection, the authors examined CD4+ lymphocyte data from 354 men who seroconverted between 1984 and 1991. To control for measurement differences among centers and over time, the authors adjusted CD4+ lymphocyte values to those of persistently seronegative participants. CD4+ lymphocyte percentage measurements at the first seropositive visit formed a U-shaped pattern, with the lowest values observed in 1988 and 1989. The authors observed no consistent secular pattern of CD4+ percentages at later visit dates, except that mean CD4+ percentages were consistently lowest in men who seroconverted in 1988. In a proportional hazards model, the time to the adjusted CD4+ lymphocyte count of < 500 cells/mm3 was not associated with the secular time of seroconversion (relative hazard = 1.05, 95% confidence interval 0.97-1.13). The authors' data do not suggest a major change in the natural history of HIV-1 infection of this population.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Risk factors for human immunodeficiency virus seroconversion among out-of-treatment drug injectors in high and low seroprevalence cities. The National AIDS Research Consortium.

From 1988 to 1991, 6,882 drug injectors in 15 US cities were interviewed and had serum samples collected. The interviews and samples were analyzed for determination of significant predictors of human immunodeficiency virus (HIV) seroconversion in the 10 low seroprevalence cities and the five high seroprevalence cities. The unit of analysis was the period of observation between consecutive paired interviews/blood samples. In Cox proportional hazards regression, significant predictors of seroconversion in the low seroprevalence cities were: not being in drug treatment, injecting in outdoor settings or abandoned buildings, using crack cocaine weekly or more frequently, engaging in woman-to-woman sex, being of non-Latino race/ethnicity, and city seroprevalence. Predictors in high seroprevalence cities were: injecting with potentially infected syringes, not being in drug treatment, and having a sex partner who injected drugs. These findings suggest that HIV may be concentrated in sociobehavioral pockets of infection in low seroprevalence cities. For reducing HIV transmission, these results suggest: 1) in low seroprevalence cities, localized monitoring to detect specific emerging sociobehavioral pockets of infection, and quick implementation of appropriate targeted interventions if necessary; 2) in high seroprevalence cities, relatively more emphasis on locality-wide outreach and syringe-exchange projects to reduce risky behavior; and 3) in both types of cities, considerable expansion of drug treatment programs.

Adult↗

PubMed1993

Late seroconversion and high chronicity rate of hepatitis C virus infection in patients with hematologic disorders.

BACKGROUND: Patients with hematologic disorders requiring repeated blood and platelet transfusions are at high risk for development of post-transfusion non-A, non-B hepatitis. PATIENTS AND METHODS: Fifty-five patients with hematologic diseases and post-transfusion non-A, non-B hepatitis were studied. Sera were assayed for hepatitis C virus (HCV) antibodies with a second-generation enzyme-linked immunoassay. Sera from 40 patients were examined for the presence of HCV RNA with a nested PCR method. RESULTS: The clinical picture of acute non-A, non-B hepatitis did not differ from that described in other patient groups: however, progression to chronic hepatitis was very common (95%). Thirty-eight (95%) of 40 patients, whose sera were analysed both serologically and for the presence of HCV RNA had verified HCV infections. In some patients time to seroconversion was prolonged, up to more than 14 months. Seventeen patients with resistant or relapsed acute leukemia were treated with combination chemotherapy during the acute or chronic phase of hepatitis. Suppression of the inflammatory activity as reflected by a decrease of serum aminotransferase levels was recorded during the subsequent pancytopenic period. CONCLUSIONS: Hepatitis C has a high chronicity rate in patients with hematologic disorders which parallels the situation of hepatitis B in the immunocompromised host. Furthermore, like the situation in hepatitis B, the hosts' immune response to infection seems to be involved in the pathogenesis of liver injury. Time to seroconversion may be prolonged and detection of HCV RNA is therefore important for diagnosis.

Adolescent↗

PubMed1991

HIV seroconversion and disinfection of injection equipment among intravenous drug users, Baltimore, Maryland.

To examine the putative protective effect of disinfectant use on HIV seroconversion among intravenous drug users, we conducted a nested case-control study comparing 22 black heterosexual HIV seroconverters with 95 persistent seronegatives matched on gender, use of cocaine, date of study entry, and duration of follow-up. For intravenous drug users who reported using disinfectant all the time, the odds of seroconversion was 0.77 (95% CI: 0.25-2.38) compared with those who reported no use of disinfectants; for those who used disinfectants some of the time, the corresponding odds ratio was 0.91 (95% CI: 0.26-3.31). The odds ratio for use of disinfectant all the time was 0.63 (95% CI: 0.10-3.91) for those injecting at galleries and 1.08 (95% CI: 0.35-3.11) for those not injecting at galleries. These data suggest a limited protective effect of disinfectant use in the field which may be more beneficial to those injecting in shooting galleries.

Adult↗

PubMed1991

Evidence of marked sexual behavior change associated with low HIV-1 seroconversion in 149 married couples with discordant HIV-1 serostatus: experience at an HIV counselling center in Zaire.

To determine the effect of an HIV-1 counselling program on 149 married Zairian couples with discordant HIV-1 serology, the rates of HIV-1 seroconversion and reported condom utilization have been observed during 382.4 person-years of follow-up (minimum follow-up time per couple of 6 months). Before determination of HIV-1 serostatus and counselling, less than 5% of these couples had ever used a condom. One month after notification of HIV-1 serostatus and counselling, 70.7% of couples reported using condoms during all episodes of sexual intercourse. At 18 months follow-up, 77.4% of the 140 couples still being followed reported continued use of condoms during all episodes of sexual intercourse. At the time of notification of HIV-1 serostatus, 18 couples experienced acute psychological distress. Home-based counselling by trained nurses resolved these difficulties in all but three couples who subsequently divorced. Intensive counselling following notification of HIV-1 serostatus led to low rates of HIV-1 seroconversion (3.1% per 100 person-years of observation) in Zairian married couples with discordant HIV-1 serostatus who voluntarily attended an HIV counselling center.

Adult↗

PubMed1992

No seroconversions among steady sex partners of methadone-maintained HIV-1-seropositive injecting drug users in New York City.

OBJECTIVE: To assess the incidence of heterosexual HIV-1 transmission from seropositive methadone-maintained injecting drug users (IDU) to their seronegative, non-IDU steady sex partners. DESIGN: A prospective, longitudinal study. SETTING: HIV-1-seropositive IDU and their HIV-1-seronegative, non-IDU steady sex partners were recruited from six methadone-maintenance clinics in the New York City boroughs of Brooklyn and Manhattan. PATIENTS, PARTICIPANTS: Between December 1988 and October 1991, 60 research participants were recruited [30 methadone-maintained, HIV-1-seropositive IDU (index subjects) and their non-IDU HIV-1-seronegative steady partners]. Baseline and follow-up (every 3-4 months) data included a structured questionnaire and blood testing for HIV infection and CD4+ cell subsets. RESULTS: Demographic characteristics of the 30 steady sex partners were evaluated as follows: sex (22 women, eight men); age (mean, 32 years; range, 21-55 years) and race (African-American, 13; Hispanic, 13; other, 4). The average duration of relationship between index subject and partner at study entry was 7.5 years (range, 4 months to 19.4 years). At entry, 27 of the 30 partners reported no or intermittent use of condoms with the index subject during a typical 12-month period. Follow-up data (median follow-up, 298 days; range, 85-992 days) were available for 22 partners. Of these, 15 reported no or intermittent condom use. For a total study observation time of 23 person-years, there were no seroconversions. The upper 95% confidence interval for the observed seroconversion rate of 0% is 13%. CONCLUSIONS: These results suggest that the likelihood of heterosexual HIV-1 transmission from seropositive methadone-maintained IDU to their seronegative, non-IDU steady sex partners is low.

Adult↗

PubMed1993

Differences in time from HIV seroconversion to CD4+ lymphocyte end-points and AIDS in cohorts of homosexual men.

OBJECTIVE: To evaluate the decline in CD4+ counts in relation to the incidence of AIDS in different cohorts of homosexual men and to quantify possible consequences of laboratory variation in CD4+ measurement. METHODS: Our study includes 403 men with well documented dates of HIV seroconversion originating from five cohort studies among homosexual men. Differences in time from HIV seroconversion to the first CD4+ count dropping < 500 or 200 x 10(6)/l and to AIDS were evaluated using Kaplan-Meier survival analyses. RESULTS: We found considerable differences between cohorts in CD4+ depletion, but not in the incidence of AIDS (1987 definition). CONCLUSIONS: Variation in CD4+ depletion appears to be mainly the result of laboratory differences. Policy recommendations on a basis of CD4+ counts probably requires a calibration of measurement. The 1993 AIDS case definition leads to a site-specific shortening of the incubation time, which complicates the study of the natural history of HIV infection and of trends in the AIDS epidemic.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Antiretroviral treatment and progression to AIDS in HIV seroconverters from different risk groups. HIV Italian Seroconversion Study.

OBJECTIVES: To evaluate the association between time since initiation of pre-AIDS antiretroviral therapy [mainly with zidovudine (ZDV)] and AIDS-free survival in a cohort of HIV seroconverters, and to assess possible differences in this association and in the use of antiretroviral therapy by HIV exposure group. DESIGN: Observational study of HIV-infected individuals, both those treated with antiretroviral therapy and those untreated, enrolled in an ongoing prospective cohort (median follow-up, 5.3. years). SETTING: Sixteen HIV outpatient clinics throughout Italy. PATIENTS: A total of 1,078 individuals infected with HIV through injecting drug use or homo-/heterosexual activity, and with accurately estimated dates of seroconversion. MAIN OUTCOME MEASURES AND METHODS: Kaplan-Meier estimates of the probability of receiving antiretroviral therapy before AIDS. Crude and adjusted relative hazards of AIDS and of death from AIDS using Cox regression models. RESULTS: The cumulative incidence of beginning pre-AIDS antiretroviral therapy within 7 years of seroconversion was 49.2%. Injecting drug users (IDU) were less likely to undergo antiretroviral treatment before AIDS than homosexual men and heterosexual contacts. The adjusted relative hazard of developing AIDS for patients treated with ZDV (relative hazard adjusted for occurrence of acute HIV disease, pre-AIDS HIV-related diseases, CD4 count, and use of prophylaxis for Pneumocystis carinii pneumonia) was 0.57 within the first year of starting zidovudine and 0.92 after 1 year of therapy. Stratifying by HIV exposure category, the adjusted relative hazards of AIDS for individuals who started ZDV less and more than 1 year before AIDS were 0.74 and 0.99 among IDU, 0.31 and 0.89 among homosexual men, and 0.69 and 0.72 among heterosexuals, respectively. Similar results were obtained when using death from AIDS as an endpoint. CONCLUSIONS: IDU began pre-AIDS antiretroviral therapy significantly later than homosexual men and heterosexuals, even after adjusting for CD4 count. Results from this non-randomized study confirm that antiretroviral treatment has only a short-term clinical benefit. There was a stronger association between antiretroviral treatment and lower risk of AIDS in homosexual men than in IDU.

Acquired Immunodeficiency Syndrome↗