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PubMed2002

Higher viral loads and other risk factors associated with HIV-1 seroconversion during a period of high incidence among injection drug users in Bangkok.

We analyzed data from a prospective cohort study of injection drug users (IDUs) attending methadone treatment clinics in Bangkok, Thailand, during 1995-1998 to characterize factors associated with a period of high incidence (PHI) from July 1996 through January 1997 compared with periods of lower incidence. Sociobehavioral characteristics were similar for all participants during and outside the PHI except for the following: there was more reported drug injection while IDUs were incarcerated during the PHI (odds ratio, 1.67; p =.02) and significantly higher proportions of persons reported heroin injection (91% vs. 75%, respectively; p =.02) and higher frequencies of daily injection and sharing of injection equipment (40% vs. 25%, respectively; p =.05) during the PHI than outside the PHI. Through most of the first year after seroconversion, plasma HIV-1 loads were significantly higher in persons who seroconverted during the PHI than in those who seroconverted outside the PHI. Higher viral loads may potentially contribute to faster disease progression and increased infectiousness or transmissibility to subsequent contacts. Our findings suggest that prevention efforts to reduce the effective size and turnover within IDU sharing networks may have a significant impact on the epidemic by disrupting the rapid transmission of HIV-1 from recently infected, highly infectious individuals.

Adult↗

PubMed2000

Low estimates of HIV seroconversions among clients of a drug treatment clinic in San Francisco, 1995 to 1998.

We estimated HIV incidence among injection drug users attending a drug treatment clinic in San Francisco from 1995 to 1998 using two methods. An anonymous sequential testing method identified no seroconversions among clients seen more than once during the period (one-sided upper 95% confidence limit 1.02 per 100 person-years). A sensitive/less sensitive immunoassay testing strategy detected no early infections (one-sided upper 95% confidence limit 1.90% per year). Methods were concordant and feasible in the setting. Although detection of no new HIV infections in this population of injection drug users (IDUs) is encouraging, epidemiologic studies among IDUs not in treatment are needed to monitor the HIV epidemic effectively.

Adult↗

PubMed2002

High incidence of HIV-1 in South Africa using a standardized algorithm for recent HIV seroconversion.

Southern Africa has among the highest rates of HIV-1 infection in the world as judged by cross-sectional HIV-1 prevalence surveys carried out among women attending antenatal clinics. Incidence rates, which provide information on the number of new cases of infection, are more informative of the current state of the epidemic than estimates of prevalence, which provide information on the rates averaged over some previous time. Cohort studies to measure incidence rates are expensive and difficult to carry out, however, and few have been done in Africa. A recently developed standardized algorithm for recent HIV-1 seroconversion (STARHS) based on a sensitive/less-sensitive enzyme-linked immunosorbent assay was used to determine the incidence of HIV-1 subtype C infection among women attending public sector antenatal clinics in Hlabisa, a rural district in KwaZulu-Natal, South Africa. The STAHRS results were confirmed by using a mathematic model to obtain an independent estimate of the age-specific incidence rates from the age-specific prevalence data. The data reveal extraordinarily high HIV-1 incidence rates in South Africa. In 1999, the annual incidence of HIV-1 among susceptible women aged 15 to 49 years standardized to the age distribution of adult women in Hlabisa was 17%. Incidence peaked among 22-year-old women at 24% per year. The HIV-1 incidence rates provide valuable additional information indicating that new infections are continuing unabated and that the HIV-1 epidemic is still growing in rural South Africa.

Adolescent↗

PubMed2004

The natural history of HIV-1 infection in young Thai men after seroconversion.

The natural history and progression of HIV-1 infection in Thailand and other developing countries in Asia and Africa have not been well defined. Nevertheless, valid data are needed to evaluate the effects of interventions, which are designed to delay progression. We evaluated the progression to AIDS and death in 235 men who seroconverted during their 2 years of service in the Royal Thai Army. The men were conscripted at age 21 and seroconverted within a 6-month window during follow-up while in the military. The seroconverters were matched with men who were seronegative when discharged. Of the HIV-positive men, 156 (66.4%) were alive, 77 (32.8%) had died, and 2 (0.8%) could not be located 5-7 years after their seroconversion and discharge from the military. The 5-year survival rate was 82.3%; the median times to clinical AIDS and a CD4 cell count of <200/microL was 7.4 years and 6.9 years, respectively. The mortality rate was 56.3 deaths per 1000 patient-years for HIV-positive men and 6.1 deaths per 1000 patient-years for HIV-negative men. Our data suggest a more rapid progression to AIDS and death after HIV-1 infection in young men in Thailand than has been reported for similarly aged cohorts in developed countries.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Long-term persistence of primary genotypic resistance after HIV-1 seroconversion.

Primary infection with drug-resistant HIV-1 is well documented. We have followed up patients infected with such viruses to determine the stability of resistance-associated mutations. Fourteen patients who experienced primary infection with genotypic evidence of resistance were followed for up to 3 years. Drug resistance-associated mutations persisted over time in most patients studied. In particular, M41L, T69N, K103N, and T215 variants within reverse transcriptase (RT) and multidrug resistance demonstrated little reversion to wild-type virus. By contrast, Y181C and K219Q in RT, occurring alone, disappeared within 25 and 9 months, respectively. Multidrug resistance in 2 patients was found to be stable for up to 18 months, the maximum period studied. We conclude that certain resistance-associated mutations are highly stable and these data support the recommendation that all new HIV diagnoses in areas where primary resistance may occur should undergo genotyping irrespective of whether the date of seroconversion is known.

Anti-HIV Agents↗

PubMed2004

Do patients who are infected with drug-resistant HIV have a different CD4 cell decline after seroconversion? An exploratory analysis in the UK Register of HIV Seroconverters.

Using data from the UK Register of HIV Sero-converters, we compared the rate of CD4 cell decline in antiretroviral-naive individuals with and without evidence of transmitted drug resistance (TDR). Although there was a suggestion that CD4 cell decline in the first year after seroconversion was faster in those with TDR,there was no evidence of a difference in the rate of decline thereafter. The virological and host determinants of this possible phenomenon are worth further exploration.

Adult↗

PubMed2004

Differences in HIV RNA levels before the initiation of antiretroviral therapy among 1864 individuals with known HIV-1 seroconversion dates.

OBJECTIVE: To assess the effects of sex, risk group, age at and year of seroconversion (SC), and presentation during acute infection on HIV RNA trends before antiretroviral therapy (ART) initiation. METHODS: Multiple HIV RNA measurements from 1864 individuals with reliably estimated dates of SC, aged >/= 15 years at SC were studied using random effects models. Models were adjusted for selective HIV RNA data truncation due to ART initiation or AIDS development and for HIV RNA quantification assay. RESULTS: HIV RNA levels declined precipitously during the first 10 months after SC followed by a slow increase. Women infected heterosexually and through injecting drug use, had an average 34% [95% confidence interval (CI), 2.3-56%] and 46% (95% CI, 17-66%) lower HIV RNA load respectively, compared to men in the same risk group. Among men, those infected heterosexually and by injecting drug use had on average 56% (95% CI, 36-69%) lower HIV RNA levels than homosexual men. Older subjects tended to have higher viral levels. There was no evidence that differences by sex, risk or age group diminished over time, but follow-up was mostly before CD4 cell count had fallen below 200 x 10 cells/l. CONCLUSIONS: HIV RNA levels at the same stage of HIV-1 infection differ significantly by sex, risk group and age at SC. Given the lack of evidence of a survival difference by sex or risk group prior to initiation of effective therapy, further research on differential effects of virus load on treatment-free disease progression is needed, before a conclusion about considering these factors for ART initiation is drawn.

Adolescent↗

PubMed2006

Effective therapy has altered the spectrum of cause-specific mortality following HIV seroconversion.

INTRODUCTION: Although HAART has led to a reduction in overall mortality among HIV-infected individuals, its impact on death from specific causes is unknown. METHODS: Twenty-two cohorts of HIV-infected individuals with known dates of seroconversion are pooled in the CASCADE collaboration. Causes of death (COD) were categorized into three AIDS-related and seven non-AIDS-related causes. The unknown causes were assigned a separate category. The cumulative incidence for each COD was calculated in the presence of the other competing COD, for the pre-HAART and HAART eras. A multivariate regression analyses for the cumulative rate of progression to the different COD was performed. RESULTS: A total of 1938 of 7680 HIV-seroconverters died. Pre-HAART, AIDS opportunistic infections (OI) was the most common COD, followed by unknown and HIV/AIDS-unspecified. In the HAART era, the cumulative incidence for all AIDS-related COD decreased, OI remaining the most important. Large reductions in death due to other infections and organ failure were seen. Cumulative death risk decreased in the HAART era for most causes. The effect of HAART was not the same for all risk groups. The cumulative risk of death from AIDS-related malignancies, OI and non-AIDS-related malignancies decreased significantly among homosexual men (MSM), whereas the risk of dying from (un)-intentional death increased significantly among injecting drug users (IDU). A non-significant increase in hepatitis/liver-related death was seen in MSM, IDU and haemophiliacs. CONCLUSION: Overall and cause specific mortality decreased following the introduction of HAART. OI remain the most common COD in the HAART era, suggesting that AIDS-related events will continue to be important in the future. Future trends in COD should be monitored using standardized guidelines.

AIDS-Related Opportunistic Infections↗

PubMed2006

Recent HIV testing among young men who have sex with men: correlates, contexts, and HIV seroconversion.

OBJECTIVES: We evaluated the correlates and contexts of HIV testing within the past year, subsequent risk reduction, and HIV seroconversion among young men who have sex with men (MSM). METHODS: Young men aged 23 to 29 years were approached, interviewed, counseled, and tested for HIV at 181 randomly sampled MSM-identified venues in six U.S. cities from 1998 through 2000. Analyses were restricted to 2,797 MSM who reported never testing HIV-positive. RESULTS: Of the 2,797 MSM, 1,281 (46%) either never previously tested or had not tested in the past year (never/remote testers); 1,516 (54%) had tested in the past year (recent testers); and 271 (10%) tested HIV-positive as part of the study. Of 1,885 recent sex partners reported by HIV-infected participants, 68% were partners of never/remote testers. Of recent testers, 50% tested anonymously, 51% tested because of specific risks, 59% were counseled, 47% reported reducing their risks after testing, and 8% tested HIV-positive (percent HIV-infected by race: blacks, 24%; Hispanics, 6%; whites, 4%; Asians, 1%). CONCLUSION: Nearly half of young MSM participants had not tested in the past year and HIV-infected never/remote testers accounted for approximately two thirds of recent partners potentially exposed to HIV. Of those who had tested recently, many MSM, especially those who are black, had already acquired HIV. To reduce HIV transmission and facilitate early diagnosis and entry into care, increased HIV testing among young at-risk MSM in the United States, especially those who are black, is needed.

AIDS Serodiagnosis↗

PubMed2005

Sexual risk, nitrite inhalant use, and lack of circumcision associated with HIV seroconversion in men who have sex with men in the United States.

Men who have sex with men (MSM) continue to account for the largest number of new HIV infections in the United States, but limited data exist on independent risk factors for infection beyond the early 1990s. The HIV Network for Prevention Trials Vaccine Preparedness Study enrolled 3257 MSM in 6 US cities from 1995 to 1997. HIV seroincidence was 1.55 per 100 person-years (95% confidence interval: 1.23-1.95) over 18 months of follow-up. On multi-variable analysis using time-dependent covariates, independent risk factors for HIV seroconversion were increased number of reported HIV-negative male sex partners (adjusted odds ratio (AOR) = 1.14 per partner, population attributable risk (PAR) = 28%), nitrite inhalant use (AOR = 2.2, PAR = 28%), unprotected receptive anal sex with an HIV unknown serostatus partner (AOR = 2.7, PAR = 15%) or HIV-positive partner (AOR = 3.4, PAR = 12%), protected receptive anal sex with an HIV-positive partner (AOR = 2.2, PAR = 11%), lack of circumcision (AOR = 2.0, PAR = 10%), and receptive oral sex to ejaculation with an HIV-positive partner (AOR = 3.8, PAR = 7%). Having a large number of male sex partners, nitrite inhalant use, and engaging in receptive anal sex explained the majority of infections in this cohort and should be targeted in prevention strategies for MSM.

Administration, Inhalation↗

PubMed2005

Use of the serologic testing algorithm for recent HIV seroconversion (STARHS) to identify recently acquired HIV infections in men with early syphilis in Los Angeles County.

BACKGROUND: Syphilis outbreaks among men who have sex with men (MSM) in the United States, many of whom are HIV infected, have prompted increased concern for HIV transmission. METHODS: To identify whether men are acquiring HIV concomitantly or within the critical period of syphilis infection, banked Treponema pallidum particle agglutination-positive serum specimens from men with early syphilis infection were screened for HIV-1 antibody. Samples that were positive for HIV antibody were then tested with a less sensitive (LS) HIV-1 antibody enzyme immunoassay (serologic testing algorithm for recent HIV seroconversion [STARHS]) to identify HIV infections that occurred on average within the previous 6 months. RESULTS: Of the 212 specimens banked from men with early syphilis, 74 (35%) were HIV-positive. Of these, 15 tested non-reactive by the LS assay. Twelve of these 15 were considered to be recent infections by the LS assay and testing history. Eleven (92%) of the recent infections were among MSM. One man had primary syphilis, 6 (50%) had secondary syphilis, and 5 (42%) had early latent syphilis. Eight men (67%) reported sex with anonymous partners, and 3 (25%) reported consistent condom use. The estimated HIV incidence was 17% per year (95% confidence interval [CI]: 12%-22%) among all men with early syphilis, and it was 26% per year (95% CI: 91%-33%) among MSM. CONCLUSIONS: Syphilis epidemics in MSM may be contributing to HIV incidence in this population. The STARHS can be applied as a surveillance tool to assess HIV incidence in various at-risk populations, but further studies are necessary for validation.

Adult↗

PubMed2006

HIV seroincidence estimates among at-risk populations in Buenos Aires and Montevideo: use of the serologic testing algorithm for recent HIV seroconversion.

Using the serological testing algorithm for recent HIV seroconversion, we estimated annualized incidences (per 100 person-years) of HIV-1 infection in different at-risk groups in Buenos Aires and Montevideo, during a 5-year period between 1998 and 2003. HIV-positive serum samples from 9 serosurveys conducted among men who have sex with men, patients attending clinics for a sexually transmitted infections consult (STIs), female commercial sex workers, injecting drug users (IDUs), noninjecting cocaine users (NICUs), asymptomatic women screened for HIV infection, and patients with tuberculosis were used. HIV incidences were as follows: 6.7 for men who have sex with men, 2.0 for STIs, 1.3 for female commercial sex workers, 0.0 for Argentinean IDUs, 10.3 for Uruguayan IDUs, 3.1 for Argentinean NICUs, 4.4 for Uruguayan NICUs, and 2.4 for patients with tuberculosis. Among asymptomatic women screened for HIV infection, incidence rose from 0.4 in 1998 to 4.6 in 1999 and to a high of 10.2 in the year 2000. Unexpectedly, high HIV incidences were detected among at-risk groups in Buenos Aires and Montevideo. This pattern shows an emerging HIV epidemic among heterosexuals stemming from core HIV-infected at-risk groups. There is an urgent need for development and implementation of specific prevention strategies to address this burgeoning epidemic.

Algorithms↗

PubMed2005

Progressive disappearance of anti-hepatitis B surface antigen antibody and reverse seroconversion after allogeneic hematopoietic stem cell transplantation in patients with previous hepatitis B virus infection.

Reactivation of resolved hepatitis B virus (HBV) infection, which is known as reverse seroconversion (RS), has been reported as a rare complication of allogeneic hematopoietic stem cell transplantation. We retrospectively studied HBV serologic markers in 14 recipients with pretransplant anti-hepatitis B surface antigen antibody (anti-HBs). Progressive decreases in anti-HBs titer were observed in all cases. In 12 cases, anti-HBs titer had decreased to under the protective value. RS occurred in seven cases after disappearance of anti-HBs. Although reseroconversion occurred in five cases, two cases remained in an HBV-carrier status after resolution of hepatitis. In the other five cases, RS did not occur even after disappearance of anti-HBs. The actual risks of anti-HBs disappearance and RS were estimated to be 75.0% and 39.8% at 2 years and 100.0% and 70.0% at 5 years, respectively. In conclusion, RS is a late-onset complication with high frequency that can be predicted by careful monitoring of progressive decrease in anti-HBs titer.

Adult↗

PubMed2004

Clinical evaluation of an HIV-1 and HCV assay and demonstration of significant reduction of the HCV detection window before seroconversion.

BACKGROUND: One HIV-1 and HCV assay simultaneously detects HIV-1 and HCV RNA (Procleix, Chiron Corp.). The main intended use of the assay is the testing of blood and blood products in blood banking. STUDY DESIGN AND METHODS: To evaluate the clinical sensitivity of the assay, 164 anti-HIV-1+ and 160 anti-HCV+ patients of different viral load were tested. The assay specificity was determined in 1000 HIV-1- and HCV-seronegative blood donors. The ability of the assay to detect different HCV genotypes was investigated in a total of 40 patients of different genotypes (1-4). Furthermore, to investigate the reduction of the HCV window phase before seroconversion, serial samples of 25 hemodialysis patients who seroconverted to anti-HCV were also tested. RESULTS: The assay detected all 60 HIV-1-infected patients with a viral load of greater than 50 copies per mL and 48 of 104 patients with a viral load of less than 50 copies per mL. Moreover, all 60 patients with an HCV RNA load of greater than 521 IU per mL and 7 of 100 patients with a viral load of less than 50 IU per mL tested positive. The assay specificity was found to be 100 percent. In addition, all 40 patients of different HCV genotypes were successfully detected. Finally, the median time that the assay detected HCV infection before second- and third-generation anti-HCV assay was found to be 183 and 91 days, respectively. CONCLUSION: The assay sensitivity and specificity, its ability to detect different HCV genotypes, and the significant reduction of window period of HCV infection further support its use for improving the safety of blood and blood products.

Antibodies, Viral↗

PubMed2004

Acute hepatitis C virus seroconversion in a Scottish blood donor: HCV antigen is not comparable with HCV nucleic acid amplification technology screening.

BACKGROUND AND OBJECTIVES: This study was conducted to analyse the usefulness of hepatitis C virus (HCV) core antigen tests for the confirmation of HCV infection in a donor presenting as nucleic acid amplification technology (NAT) positive but negative for antibodies to HCV (anti-HCV). MATERIALS AND METHODS: Blood donations were screened, in parallel, for anti-HCV using the Abbott PRISM HCV Chemiluminescent immunoassay (ChLIA) and an 'in-house' HCV NAT (pools of up to 95 donations). An HCV NAT-positive antibody-negative donor was identified. Twelve follow-up samples were obtained and tested with various HCV antigen (including the recently marketed Trak-C second-generation assay) and HCV antibody assays. RESULTS: The single HCV NAT-positive, antibody-negative donation was identified from 1 117 681 donations screened in the 4-year period, July 1999 to June 2003. The index donation was positive by Ortho HCV core antigen enzyme immunoassay (EIA) and Ortho Trak-C (second-generation HCV core antigen EIA). An archive sample, taken 127 days prior to the index donation, was negative for all HCV markers. Subsequent samples demonstrated a loss of reactivity in the Ortho HCV core antigen EIA and reduced activity in the Ortho Trak-C until day 69. Immunoblot (Ortho RIBA-3) and HCV PRISM became positive on day 62, whilst Ortho HCV ELISA was not positive until day 132 or Biorad HCV ELISA until day 160. An alternative immunoblot (Innogenetics Innolia III) was positive from day 55. RNA levels fluctuated considerably during the follow-up period, being completely undetectable by routine screening methods at the time-point around seroconversion; subsequently, antibody was detected using all assays investigated. CONCLUSIONS: This HCV-converting blood donor provided a unique panel of samples for using to assess current (and future) HCV assay systems. The overall test results led to the conclusion that individual HCV antigen testing should not be considered as equivalent to HCV NAT minipool screening. Trak-C antigen testing may be considered as a suitable confirmatory assay for isolated HCV NAT reactivity.

Acute Disease↗

PubMed1979

Seroconversion to human-cytomegalovirus-specific pre-early nuclear antigens in renal transplant recipients.

Seroconversion to human cytomegalovirus (H-CMV)-specific antigens was observed in 8 out of 9 renal transplant recipients. In 7 of the 8 recipients antibody to "pre-early nuclear antigens" (PENA), which are detectable in human embryonic lung cells within 1 hr of H-CMV infection by anti-complement immunofluorescence staining, developed concomitantly with the increase in other antibodies including anti-early antigens (EA), anti-nuclear inclusions (NI), and complement-fixing (CF) antibody in 1--2 months after transplantation. About 1 year later, anti-PENA and anti-EA titers were concomitantly decreased in 2 recipients, whereas anti-NI and CF antibody titers were maintained at elevated levels in all the seroconverted recipients. These results support the idea that the development of antibody to PENA, like antibody to EA, may represent a current or recent infection with (or reactivation of) H-CMV. In one patient, antibody to PENA did not develop through the observation period despite increases in antibody to EA and other antibodies; this lends support to immunological distinctness of PENA from EA.

Adult↗

PubMed1986

Acute HTLV III infection associated with exanthema, diagnosed by seroconversion.

We report three homosexual men who developed malaise, fever and a roseola-like exanthema which disappeared over 2 weeks. During 3 months follow-up, all three patients felt well and had no symptoms. HTLV III seroconversion was detected several weeks after the acute HTLV III infection. In two of the three cases the Western blot technique was able to detect HTLV III antibodies before they were detectable by the ELISA technique.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Anti-HCV seroconversion in multitransfused and immunocompromised patients. A long-term longitudinal study.

In a series of 6 multitransfused, immunocompromised patients, the diagnosis of posttransfusion hepatitis C was based upon the analysis of long-term follow-up serum samples. The HCV RNA was detected by a nested PCR assay using primers located in the 5' noncoding region (5'NCR), and anti-HCV antibodies were assayed with third-generation tests. The interval between the first rise in alanine aminotransferase and seroconversion varied from less than 5 months to more than 38 months. Five out of 6 patients seroconverted after 14 months or later. In most cases, the anti-NS3 and anti-NS4 antibodies appeared first. In such patients, the etiology of chronic liver disease may thus be overlooked for 1 or more years, a definitive diagnosis requiring the detection of HCV RNA.

Adult↗