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Evaluation of a sensitive/less-sensitive testing algorithm using the 3A11-LS assay for detecting recent HIV seroconversion among individuals with HIV-1 subtype B or E infection in Thailand.

The development of a serologic algorithm to determine recent HIV seroconversion, using sensitive/less-sensitive testing strategies, has generated widespread interest in applying this approach to estimate HIV-1 incidence in various populations around the world. To evaluate this approach in non-B subtypes, longitudinal specimens (n = 522) collected from 90 incident infections among injecting drug users in Bangkok (subtype B infection, n = 18; subtype E infection, n = 72) were tested by the 3A11-LS assay. Standardized optical density (SOD) was calculated, using median values, and the window period between seroconversion as determined by sensitive and less sensitive tests was estimated by a maximum-likelihood model described previously. Our results show that the mean window period of the 3A11-LS assay was 155 days (95% CI, 128-189 days) for subtype B but was 270 days (95% CI, 187-349 days) for subtype E specimens from Thailand. About 4% of individuals with incident subtype E infections remained below the threshold (SOD of 0.75), even 2 years after seroconversion. Among the patients with clinical AIDS and declining antibodies, none of the 7 individuals with subtype B, but 10 (8.7%) of 115 with subtype E infections, were misclassified as recent infections. Lowering the cutoff to an SOD of 0.45 for subtype E specimens resulted in a mean window period of 185 days (95% CI, 154-211 days), with all individuals seroconverting, and reduced the number of subtype E-infected patients with AIDS who were misclassified as having recent infection to 2.6%. Our results demonstrate that the 3A11-LS assay has different performance characteristics in detecting recent infections among individuals infected with subtypes B or E. Determining appropriate cutoffs and mean window periods for other HIV-1 subtypes will be necessary before this approach can be reliably implemented in settings where non-B subtypes are common.

Adult↗

Effect of breast-feeding on oral rhesus rotavirus vaccine seroconversion: a metaanalysis.

The effect of concomitant breast-feeding on seroconversion following oral administration of rhesus rotavirus vaccine (RRV, serotype 3, strain MMU 18006) at 10(4) pfu was analyzed. Three studies were included, all randomized, double-blind trials involving a single dose of RRV to infants aged 2-5 months. None received concomitant oral polio vaccine. Seroconversion was measured by microneutralization or tube neutralization assay. The results show that 42 (48%) of 88 (95% confidence interval, 37%-58%) breast-fed babies seroconverted compared with 62 (70%) of 88 (95% confidence interval, 61%-80%) bottle-fed babies (chi 2 = 9.35, P less than .005). Thus, there was a significant adverse effect of breast-feeding with respect to RRV vaccine seroconversion.

Administration, Oral↗

Incidence of human T lymphotropic virus type I seroconversion after age 40 among Japanese residents in an area where the virus is endemic.

To clarify how seroconversion after age 40 years contributes to the seroprevalence of human T lymphotropic virus type I (HTLV-I), Japanese residents were studied in an area of Kyushu in which HTLV-I is endemic. Cross-sectional data showed higher seroprevalences among subjects > or = 40 than in those < 40 years old (27.0% vs. 7.9%). The prevalence was also greater in women than men (25.5% vs. 17.6%). Six hundred subjects > or = 40 years old were tested during 1976-1993. Among 8 who seroconverted, 5 had an HTLV-seropositive spouse and 2 seroconverted after blood transfusions. The incidences per 1000 person-years of seroconversion in age groups 40-49, 50-59, and > or = 60 years were, respectively, 0.0, 0.0, and 3.3 (range, 1.38-5.13) in men and 0.0, 5.3 (range, 0.11-7.99), and 1.4 (range, 0.00-1.60) in women. The seroconversion incidence was insufficient to account for the rise of seroprevalence in those > or = 40 years old, especially among women. These results suggest that the high rate and sex discordance in HTLV-I seroprevalence after age 40 may depend mainly on the birth cohort effect for vertical or horizontal transmission.

Adult↗

Incidence and predictors of human immunodeficiency virus type 1 seroconversion in patients attending sexually transmitted disease clinics in India.

The first estimates of the seroincidence of human immunodeficiency virus type 1 (HIV-1) and of the risk factors for seroconversion in a cohort of high-risk patients attending sexually transmitted disease (STD) clinics in India are reported. Between 1993 and 1995, 851 HIV-1-seronegative persons were evaluated prospectively every 3 months for HIV infection and biologic and behavioral characteristics. The overall incidence of HIV-1 was 10.2/100 person-years (95% confidence interval, 7.9-13.1). The incidence among commercial sex workers (CSWs) was 26.1/100 person-years, compared with 8.4 among non-CSWs. Recurrent genital ulcer disease and urethritis or cervicitis during the follow-up period were independently associated with a 7- (P < .001) and 3-fold (P = .06) increased risk of HIV-1 seroconversion, respectively. Because of the association of recurrent ulcerative and nonulcerative STDs with HIV-1 seroconversion in this setting, behavioral and biologic measures directed at the prevention and control of STDs would be expected to greatly reduce the transmission of HIV-1 infection in similar high-risk groups.

Adult↗

Ignorance of post-exposure prophylaxis guidelines following HIV needlestick injury may increase the risk of seroconversion.

Needlestick injury is relatively common amongst healthcare workers, particularly those, such as anaesthetists, who regularly perform invasive procedures. The risk of seroconversion following needlestick injury may be reduced by knowledge of body fluids that are high risk and knowledge of post-exposure prophylaxis following possible HIV-contaminated needlestick injury. A structured questionnaire was used to establish knowledge regarding high HIV risk body fluids and measures to be taken following needlestick injury in anaesthetists working in a large teaching hospital. Completed questionnaires were obtained from all 76 anaesthetists working in the department (39 consultant, 37 trainee/non-consultant). Only 45.2% correctly identified high-risk body fluids. Sixty-eight per cent of anaesthetists knew the appropriate first aid measures to be taken following needlestick injury. Only 15% of anaesthetists were aware that post-exposure prophylaxis (oral medication) should be administered within 1 h of injury. This study reveals a surprisingly poor knowledge of high-risk body fluids and action to be taken following needlestick injury. Timely post-exposure prophylaxis, after needlestick exposure to high-risk body fluids, is believed to reduce the risk of seroconversion to HIV. Ignorance of this may increase the risk of seroconversion to HIV for anaesthetists and other healthcare professionals.

Anesthesiology↗

Differences in progression to AIDS between injection drug users and homosexual men with documented dates of seroconversion.

We compared rates of progression to AIDS for 99 injection drug users and 120 homosexual men with documented dates of HIV-1 seroconversion. The crude risk of developing AIDS was higher among homosexual men than injection drug users [relative hazard (RH) = 2.4; 95% confidence interval (CI) = 1.3-4.4]. The relative hazard was slightly smaller among participants with a seroconversion interval of < or = 1 year (RH = 2.2; 95% CI = 1.0-5.2). The effect was partially explained by the inclusion of Kaposi's sarcoma in the AIDS case definition. Excluding those with Kaposi's sarcoma, the relative hazard was 2.0 (95% CI = 1.1-3.8). Using the 1993 AIDS case definition decreased the effect (RH = 1.9; 95% CI = 1.1-3.4). Finally, the high pre-AIDS mortality among injection drug users could partially explain the difference in progression rate between injection drug users and homosexual men. Combining the effect of the above-mentioned factors resulted in a relative hazard of 1.3 (95% CI = 0.7-2.6). Thus, the slower progression to AIDS among injection drug users compared with homosexual men was largely explained by differences in the spectrum of AIDS-defining illnesses, pre-AIDS mortality, and length of seroconversion interval.

Acquired Immunodeficiency Syndrome↗

Factors related to seroconversion among homo- and bisexual men after attending a risk-reduction educational session.

Thirteen homosexual men, volunteers in a study of the natural history of HIV, who seroconverted to HIV after participating in an educational program on HIV prevention, were interviewed about the circumstances leading to their seroconversion. Six men had participated in unprotected anal intercourse with at least one partner whom they believed was HIV-negative. Four men attributed their conversion to mental health problems or to drug and alcohol use. Two men's seroconversions could not be ascertained and one man attributed seroconversion to a condom break. Most men who had learned how to avoid infection, and had successfully done so for a time, had knowingly engaged in unsafe behaviors because of strong emotional responses to certain partners or because of mental health or drug and alcohol-related problems. Skills training for dealing with partners who pressure men to behave unsafely is needed, as is mental health and drug and alcohol counseling for men at risk for HIV infection.

Acquired Immunodeficiency Syndrome↗

Immunological and virological markers in individuals progressing from seroconversion to AIDS.

Six men were selected from a large cohort of homosexual men participating in a study on HIV infection that was followed from seroconversion to AIDS. The patients were studied retrospectively for immunological functions of T cells, T-cell subset distribution and biological phenotype of HIV. A severe decrease in anti-CD3 monoclonal antibody (MAb)-induced T-cell proliferation at seroconversion was observed in two out of six men. After this acute phase, CD4+ T-cell numbers were in the normal range in the early asymptomatic period; the proliferative response was subnormal, whereas the capacity to generate cytotoxic T cells (CTL) was normal. From seroconversion on, CD4+CD29+ memory T-cell numbers were decreased to approximately 50% of normal values, which may contribute to loss of T-cell reactivity. In the asymptomatic phase only slow-replicating non-syncytium-inducing HIV variants were observed. The T-cell proliferative response further declined with the depletion of naive CD4+ CD45RA+ T cells and CD4+ T-cell numbers started to decline. This second decrease in T-cell function coincided with the emergence of more rapidly replicating, often (four out of six) syncytium-inducing variants. At diagnosis of AIDS, T-cell proliferation and CD4+ T-cell numbers were extremely low in five out of six patients and CTL function had declined in three out of five individuals tested. Circulating CD8+ cells had gradually shifted to an immature CD38+CD28- phenotype. Our findings support the theory that HIV-induced immune dysfunction allows for the emergence of virulent HIV variants associated with CD4+ cell loss and disease.

Acquired Immunodeficiency Syndrome↗

Development of HIV-1 group-specific neutralizing antibodies after seroconversion.

OBJECTIVE: To study the induction of group-specific (gs) neutralizing antibodies to HIV-1 after seroconversion. DESIGN AND METHODS: Serum samples taken sequentially from seven Dutch homosexual men and four British haemophiliacs (anonymous sample, therefore sex not known) before and after seroconversion were tested for neutralizing antibodies effective against five diverse HIV-1 strains. Strains of HIV-1 tested included isolates from the United States, Europe and Africa. RESULTS: The gs neutralizing antibody response varied between individuals. Only five of the 11 individuals studied produced detectable neutralizing antibodies to laboratory-adapted HIV-1 strains (for example, IIIB) within 32 weeks of seroconversion. Most individuals initially produced antibodies effective against US/European isolates; the response then generally broadened to include the more diverse strains, i.e., African. CONCLUSIONS: These results suggest that the gs neutralizing target for HIV-1 is poorly immunogenic in vivo and is probably not highly conserved among diverse HIV-1 strains.

HIV Antibodies↗

Seroconversion in patients attending sexually transmitted disease clinics.

OBJECTIVES: To characterize recent HIV seroconverters in a sexually transmitted disease (STD) clinic population, and examine changing transmission patterns. METHODS: We conducted a case-control study nested within a retrospectively defined cohort of individuals attending Baltimore STD clinics between January 1988 and July 1990. Seroconverters, who tested HIV-positive after having a negative test, were compared to both HIV-negative controls, who were also tested twice, and a second, prevalent HIV-positive control group. Controls were matched 2:1 by sex, clinic, and month of HIV test. RESULTS: Forty-nine out of 6175 (0.79%) patients tested at least twice had documented HIV-1 seroconversion. On multivariate analysis, seroconversion was significantly associated with self-reported injecting drug use [odds ratio (OR), 7.3; 95% confidence interval (CI), 2.3-23)], with being a man who has had sex with other men (OR, 3.5%; 95% CI, 1.2-10), or with having sex with a known HIV-infected person (OR, 11; 95% CI, 1.3-96). Thirty-five per cent of seroconverters did not report a risk for HIV infection, and a higher proportion of recent seroconverters also reported no risk. Compared to the prevalent positive control group, more seroconverters reported no risk and a lower proportion reported recognized risks. A diagnosis of gonorrhea was also significantly associated with seroconversion (OR, 2.5; 95% CI, 1.1-5.7). CONCLUSIONS: These data suggest increasing heterosexual transmission of HIV in this inner-city STD clinic population. Incident STD, in particular gonorrhea, may increase a patient's risk for HIV infection, suggesting that patients with STD should be targeted aggressively for HIV prevention activities.

Adult↗

HIV-1 seroconversion rates among female commercial sex workers, Chiang Mai, Thailand: a multi cross-sectional study.

OBJECTIVES: To determine HIV seroconversion rates among female commercial sex workers (CSW) in Chiang Mai, Thailand. DESIGN: A three-round multi cross-sectional study was used at approximately 3-month intervals. METHODS: In December 1989, 38 brothels (60%) in Chiang Mai were randomly selected. All 518 female CSW in the brothels were interviewed about their sociodemographics, sexual practices, condom use, history of sexually transmitted diseases (STD) and other risk factors. Blood was tested for Venereal Disease Research Laboratory (VDRL)-reactivity and HIV-1 antibody. The same brothels, which were all still operating, were revisited in March and July 1990 and 431 and 320 CSW, respectively, were interviewed and blood-tested. Pelvic examination, cervical, urethral and rectal cultures for gonococcus were added to the study in March 1990, although rectal culture was dropped from the study in July 1990. RESULTS: There were 5.2% [95% confidence interval (CI), 4.1-10.6] and 3.6% (95% CI, 1.5-5.4) per woman-month HIV seroconversion rates for the December-March and March-July periods, respectively. Of the CSW, 71.6-77.0% reported histories of at lest one STD. Condom-use rates among these CSW were reported to be 85.8-91.8%. High rates of positive cervical (11.2-12.3%) and urethral (8.8-11.4%) cultures for gonococcus were also found in the CSW. CONCLUSIONS: The fact that high HIV seroconversion rates and high STD prevalence rates occur despite high rates of reported condom use suggests that more aggressive education programs are needed in Thailand.

Contraceptive Devices, Male↗

HIV-1 seroconversion in a prospective study of female sex workers in northern Thailand: continued high incidence among brothel-based women.

OBJECTIVES: To determine the incidence of HIV-1 infection, temporal trends in incidence, and risk factors for seroconversion in a cohort of female commercial sex workers (CSW) in upper northern Thailand, the region of Thailand with the highest rates of HIV-1 infection. METHODS: CSW were enrolled from 1991 through 1994 and evaluated prospectively with interviews, physical examination, testing for sexually transmitted diseases (STD), and serologic testing for HIV-1 infection. RESULTS: The incidence of HIV-1 seroconversion in the first year of follow-up was 20.3 per 100 person-years among 126 brothel-based CSW and 0.7 per 100 person-years among 159 other CSW who worked in other venues such as bars or massage parlors. Incidence remained elevated among brothel-based CSW who were enrolled later in the study compared with those who enrolled earlier. Through 1996, 30 women seroconverted. In a multivariable proportional hazards model, seroconversion was significantly associated (P < 0.05) with brothel-based sex work (adjusted risk ratio, 7.3) and Chlamydia trachomatis cervical infection (adjusted risk ratio, 3.3). CONCLUSION: Despite national HIV control efforts and declining rates of infection among young men in Thailand, brothel-based CSW may continue to be at high risk for HIV-1 infection. Additional efforts are needed to provide alternative economic choices for young women, to ensure universal condom use during commercial sex, and to develop new prevention technologies.

Adolescent↗

Effect of ignoring the time of HIV seroconversion in estimating changes in survival over calendar time in observational studies: results from CASCADE.

OBJECTIVE: To compare estimates of changes in HIV survival over time derived from seroconverter and prevalent cohorts. DESIGN AND METHODS: Using pooled data from 19 seroconverter cohorts (CASCADE), the relative risk of death from HIV seroconversion by calendar time at risk from 1 January 1991 was examined. The analyses were repeated, ignoring knowledge of the time of seroconversion, but adjusting for the CD4 cell count at the time the participant came under observation, thus mimicking a prevalent cohort. Estimates from the 'prevalent' cohort approach were compared with those obtained from the seroconverter cohort. RESULTS: Of 5428 subjects at risk on 1 January 1991 or later, 1312 (24.2%) had died. In the analysis based on time from seroconversion, estimates of the effect of calendar year showed marked reductions in mortality in 1997-1999 only, with no evidence of a linear trend over the period 1991-1996 (P-trend = 0.85). Using the prevalent cohort approach a decrease in the relative risk of death was observed from 1991 to 1998-1999, with a statistically significant trend of a decrease in risk from 1991 to 1996 (P-trend = 0.002). Similar findings were observed when the analyses was repeated taking the start date of the cohort as 1 January 1988. CONCLUSION: Lack of knowledge of HIV infection duration may lead to biased and exaggerated estimates of survival improvements over time. The adjustment for duration of infection in prevalent HIV cohorts through laboratory markers may compensate inadequately for this.

Adolescent↗

Sexual adventurism, high-risk behavior, and human immunodeficiency virus-1 seroconversion among the Chicago MACS-CCS cohort, 1984 to 1992. A case-control study.

BACKGROUND AND OBJECTIVES: To predict incident human immunodeficiency virus (HIV)-1 seroconversions among a cohort of gay and bisexual men based on recalled sexual behavior, drug use, partnership status, and an index of sexual adventurism/risk-seeking attitudes. STUDY DESIGN: A nested case-control design was used in a retrospective study spanning a 9-year period. RESULTS: Sexual adventurism was an important predictor of HIV-1 infection. The partial risk ratio for our 100-point adventurism scale indicated a marginal rate of increase in seroconversion risk of 4% (odds ratio = 1.04; 95% confidence interval = 1.02 to 1.06), with almost 79% of seroconverters scoring above the median on the index. As expected, partner status, drug use, and unprotected receptive anal (RA) intercourse were associated with seroconversion. However, multivariate results indicated that men using condoms consistently in RA sex were also at higher risk for infection (odds ratio = 2.68; 95% confidence interval = 1.04 to 6.95) than men who abstained from RA intercourse. CONCLUSIONS: Results are discussed with respect to their implications for HIV prevention intervention and research. Recommendations include the development of new approaches and the adaptation of existing intervention techniques that recognize and treat persons with strong risk-taking predispositions.

Adult↗

Time course of seroconversion by HerpeSelect ELISA after acquisition of genital herpes simplex virus type 1 (HSV-1) or HSV-2.

BACKGROUND: HerpeSelect HSV-1 and HSV-2 ELISAs are glycoprotein G-based, type-specific antibody detection tests that are approved by the US Food and Drug Administration for diagnosis of genital herpes. GOAL: The goal was to determine seroconversion times by means of HerpeSelect ELISAs. STUDY DESIGN: Four-hundred thirteen sera from 113 patients with recently acquired genital herpes were tested by HerpeSelect ELISAs and Western blot (WB). Thirty-one patients had primary genital HSV-1 (group 1), 56 had primary HSV-2 (group 2), and 26 had prior HSV-1 antibodies and newly acquired HSV-2 (group 3). RESULTS: Median interval from onset of symptoms to seroconversion was 25 days, as determined by HerpeSelect HSV-1, versus 33 days by WB for group 1; 21 days by HerpeSelect HSV-2 versus 40 days by WB (group 2; P = 0.0005); and 23 days by HerpeSelect HSV-2 ELISA versus 47 days by WB (group 3; P = 0.02). In long-term follow-up, transient reversion to HerpeSelect negativity occurred in 3 of 31 HSV-1-infected subjects (10%) and in 2 of 82 HSV-2-infected subjects (2%). CONCLUSION: Seroconversion to HSV-2 was determined faster by HerpeSelect than by WB.

Antibodies, Viral↗

Analysis of an HIV-infected cohort followed for as long as 15 years after seroconversion.

Data from a cohort of 62 HIV-positive individuals with hemophilia or von Willebrands disease infected for a maximum period of 15 years were analyzed. The relation between CD4+ and total lymphocyte counts and their rate of decline was analyzed with respect to age at seroconversion, time of seroconversion, and development of disease and subsequent death. As expected, the CD4+ and total lymphocyte population decline correlated with increased probability of disease and death. The patients fell into two distinct categories with respect to this decline: those whose cell count declined steadily (single slope) and those whose cell count remained steady or decreased very slowly for a variable period and then declined sharply (double slope). Within this cohort, the presence of a double slope appears to indicate a poorer prognosis, as 9 of 18 of the patients who have died showed this pattern, whereas only 6 of 42 of the remaining patients have this pattern even though more than half of this group have CD4+ lymphocyte counts < 0.2 x 10(9)/L. In addition, the ratio of CD4+ lymphocyte count to total lymphocyte count decreased with increasing cumulative frequency of the cumulative incidence of disease and death and the overall probability of death in this cohort was lower than expected, being 30% 12 years after seroconversion.

Adult↗

Determinants of progression to AIDS in HIV-infected individuals: an update from the Italian Seroconversion Study.

The Italian Seroconversion Study (ISS) involves 16 major HIV-treatment centers across Italy and about 1,200 individuals. These individuals were HIV-negative less than 2 years before the first positive test and seroconverted between 1980 and 1994. The majority were infected through i.v. drug use (56%), male-to-male sex (25%), and heterosexual contact (7%). For each end point, crude and adjusted relative hazards were calculated using standard survival techniques such as Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression models. Autoregression models were used to describe CD4 cell reductions. Objectives were as follows: to estimate HIV disease progression rates; to assess whether there are differences in the rate of development of severe immunosuppression, AIDS, and death according to age, gender, and exposure category; to identify co-factors and predictors of disease progression; and to evaluate the clinic-based population "effect" of antiretroviral treatment. The risk for developing AIDS among individuals in the ISS cohort was less than 50% by 10 years after HIV seroconversion. Using univariate analysis, more rapid progression was found for older individuals than for younger individuals and for homosexual men compared with those in other exposure categories. No difference between men and women was observed. After adjusting for age, differences among exposure groups disappeared. Individuals with a history of acute HIV disease were more likely to develop AIDS than other seroconverters. Co-infection with HCV and HTLV-II did not accelerate progression to AIDS. The cumulative incidence of receiving pre-AIDS therapy within 7 years of seroconversion was 49.2% (95% CI 45.3-53.0). The relative hazards of developing AIDS in patients who started treatment with zidovudine (AZT) monotherapy was 0.57 (0.36-0.91) and 0.92 (0.64-1.33) within the first year and after 1 year from AZT initiation, respectively. The effect was greater among homosexual men than among i.v. drug users. In conclusion, incident cohort studies may provide accurate information on incubation time and co-factors for disease progression. Observational studies may also provide useful information about the effect of treatment at the community level, which may complement the results of clinical trials.

Acquired Immunodeficiency Syndrome↗

Low carotenoid concentration and the risk of HIV seroconversion in Pune, India.

Low vitamin A and carotenoid levels could increase the risk of sexual HIV acquisition by altering the integrity of the genital epithelium or by immunologic dysfunction. We addressed this issue by measuring serum vitamin A and carotenoid levels in patients who were at risk of subsequent HIV infection. In a nested case-control study in individuals attending two sexually transmitted disease (STD) clinics in Pune, India, serum micronutrient levels were measured in 44 cases with documented HIV seroconversion (11 women and 33 men) and in STD patients matched for gender and length of follow-up with no subsequent HIV seroconversion (controls). STD patients in Pune had low vitamin A and carotenoid levels, and low serum beta-carotene levels were independently associated with an increased risk of subsequent HIV seroconversion. STD patients with beta-carotene levels less than 0.075 micromol/L were 21 times more likely to acquire HIV infection than those with higher levels (adjusted odds ratio = 21.1; p =.01). No such association was observed in case of other non-provitamin A carotenoids. This study reports the first evidence of an association between low serum provitamin A carotenoid levels and an increased risk for heterosexual HIV acquisition in STD patients in Pune, India.

Adolescent↗