Ernest Wong

Routine surveillance for the detection of acute and recent HIV infections and transmission of antiretroviral resistance

Objective:To estimate the rate of acute and recent HIV infections and the prevalence of primary antiretroviral resistance. Design, setting, and subjects:A consecutive sample of individuals presenting for HIV testing at the San Francisco municipal sexually transmitted diseased (STD) clinic in 2004 (n = 3789). Main outcome measures:HIV antibody-positive specimens were screened by BED IgG capture enzyme immunoassay to identify recent infections. HIV antibody-negative specimens were screened by nucleic acid amplification testing (NAAT) to detect acute infections. Newly detected infections were genotyped to detect primary antiretroviral resistance. Results:There were 11 acute and 44 recent HIV infections among the total 136 newly detected cases. NAAT increased case identification by 8.08% over standard antibody testing. Acute HIV infections were associated with having a known HIV-positive partner, and a history of hepatitis B, syphilis, and chlamydia. The prevalence of primary antiretroviral resistance was 13.2%, with drug-resistant mutations detected in 17 of 129 cases genotyped. Mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) were present in 11 of 17 cases. Conclusion:The integration of HIV nucleic acid amplification, recent infection, and antiretroviral resistance testing enhanced HIV/STD surveillance. The high proportion of NNRTI mutations detected suggests they may be more common in source partners or more fit for transmission than other forms of drug-resistant HIV-1. Primary antiretroviral resistance monitoring in STD clinic patients may guide the selection of treatment and post-exposure prophylaxis regimens active against viruses being transmitted in the community, and provide health departments with surveillance data in a sentinel population at risk of HIV transmission.

Feasibility, acceptability, and cost of tuberculosis testing by whole-blood interferon-gamma assay.

BackgroundThe whole-blood interferon-gamma release assay (IGRA) is recommended in some settings as an alternative to the tuberculin skin test (TST). Outcomes from field implementation of the IGRA for routine tuberculosis (TB) testing have not been reported. We evaluated feasibility, acceptability, and costs after 1.5 years of IGRA use in San Francisco under routine program conditions.MethodsPatients seen at six community clinics serving homeless, immigrant, or injection-drug user (IDU) populations were routinely offered IGRA (Quantiferon-TB). Per guidelines, we excluded patients who were <17 years old, HIV-infected, immunocompromised, or pregnant. We reviewed medical records for IGRA results and completion of medical evaluation for TB, and at two clinics reviewed TB screening logs for instances of IGRA refusal or phlebotomy failure.ResultsBetween November 1, 2003 and February 28, 2005, 4143 persons were evaluated by IGRA. 225(5%) specimens were not tested, and 89 (2%) were IGRA-indeterminate. Positive or negative IGRA results were available for 3829 (92%). Of 819 patients with positive IGRA results, 524 (64%) completed diagnostic evaluation within 30 days of their IGRA test date. Among 503 patients eligible for IGRA testing at two clinics, phlebotomy was refused by 33 (7%) and failed in 40 (8%). Including phlebotomy, laboratory, and personnel costs, IGRA use cost

Exploring the relationship between sexually transmitted diseases and HIV acquisition by using different study designs

33.67 per patient tested.ConclusionIGRA implementation in a routine TB control program setting was feasible and acceptable among homeless, IDU, and immigrant patients in San Francisco, with results more frequently available than the historically described performance of TST. Laboratory-based diagnosis and surveillance for M. tuberculosis infection is now possible.

Low incidence and prevalence of hepatitis C virus infection among sexually active non-intravenous drug-using adults, San Francisco, 1997-2000.

Background:It is hypothesized that sexually transmitted diseases (STDs) increase the risk of HIV acquisition. Yet difficulties establishing an accurate temporal relation and controlling confounders have obscured this relationship. In an attempt to overcome prior methodologic shortcomings, we explored the use of different study designs to examine the relationship between STDs and HIV acquisition. Methods:Acutely HIV-infected patients were included as cases and compared with (1) HIV-uninfected patients (matched case-control), (2) newly diagnosed chronically HIV-infected patients (infected analysis), and (3) themselves at prior clinic visits when they tested HIV negative (case crossover). We used t tests to compare the average number of STDs and logistic regression to determine independent correlates and the odds of acute HIV infection. Results:Between October 2003 and March 2007, 13,662 male patients who had sex with men were tested for HIV infection at San Franciscos municipal STD clinic and 350 HIV infections (2.56%) were diagnosed. Among the HIV-infected patients, 36 cases (10.3%) were identified as acute. We found consistently higher odds of having had an STD within the 12 months [matched case-control, odds ratio 5.2 (2.2-12.6); infected analysis, odds ratio 1.4 (1.0-2.0); and case crossover, odds ratio 1.3 (0.5-3.1)] and 3 months [matched case-control, odds ratio 34.5 (4.1-291.3); infected analysis, odds ratio 2.3 (1.1-4.8); and case crossover, odds ratio 1.8 (0.6-5.6)] before HIV testing among acutely HIV-infected patients. We found higher odds of acute HIV infection among patients with concurrent rectal gonorrhea [17.0 (2.6-111.4), P < 0.01] or syphilis [5.8 (1.1-32.3), P = 0.04] when compared with those HIV-uninfected patients. Conclusions:Acute HIV infection was associated with a recent or concurrent STD, particularly rectal gonorrhea, among men at San Franciscos municipal STD clinic. Given the complex relationship between STDs and HIV infection, no single design will appropriately control for all the possible confounders; studies using complementary designs are required.

Assessment of rapid tests for detection of human immunodeficiency virus-specific antibodies in recently infected individuals.

Background The rate of sexual transmission of hepatitis C virus (HCV) is debated. Goal The goal was to measure the risk of sexual transmission of hepatitis C virus (HCV) in a sexually active population. Study Design Sexual behaviors and HCV antibody status were measured in persons seeking repeat HIV testing in San Francisco from October 1997 through March 2000. Results Among 981 repeat testers, the prevalence of HCV antibody was 2.5%. Among men who have sex with men who denied intravenous drug use (n = 746), factors associated with HCV antibody positivity include age greater than 50 years (odds ratio [OR], 8.5; 95% confidence interval [CI], 2.6–27.7), HIV infection (OR, 5.7; 95% CI, 1.6–20.6), and being nonwhite (OR, 3.3; 95% CI, 1.1–10.0). HCV antibody positivity was not associated with sexual risk behaviors. In 576.6 person-years of observation, no new HCV seroconversions occurred (incidence = 0 per 100 person-year; 95% CI, 0–.6), whereas 6 new herpes simplex virus-2 infections (2.8 per 100 person-years) and 10 new HIV infections (1.8 per 100 person-years) occurred. Conclusion The absence of new HCV infections in this sample supports the hypothesis that the risk of sexual transmission of HCV is low.

Incidence and prevalence of herpes simplex virus type 2 infection in persons seeking repeat HIV counseling and testing.

ABSTRACT We have evaluated four current Food and Drug Administration-cleared rapid tests for human immunodeficiency virus (HIV)-specific antibodies with a panel of specimens from recently infected individuals. Recent infection was detected by RNA-based screening coupled with enzyme immunoassay-based testing. We found that the sensitivities of the various rapid tests vary greatly with regard to their ability to detect HIV-specific antibodies in recently infected individuals.

Serologic herpes testing in the real world: validation of new type-specific serologic herpes simplex virus tests in a public health laboratory.

Background Voluntary HIV testing sites provide an opportunity to identify and counsel persons with herpes simplex virus type 2 (HSV-2) infection, thereby enhancing the prevention of HSV-2 and HIV infections. Goal and Study Design Using serologic specimens left over from HIV testing, we measured HSV-2 prevalence and incidence among persons who had repeatedly tested for HIV at anonymous counseling and testing sites in San Francisco during the period October 1997 through March 2000. Results The prevalence of HSV-2 infection was 23.5% (n = 987) overall, 28.7% among women, and 24.1% among men who have sex with men (MSM). In relation to race/ethnicity, HSV-2 prevalence was highest among African Americans (34.4%). The incidence of HSV-2 infection (n = 457 person-years [PY] of follow-up) was 2.6 per 100 PY overall and 3.1 per 100 PY among MSM. All but one of the HSV-2 seroconversions occurred among MSM. In multivariate subanalysis of MSM, a self-reported sexually transmitted disease (hazards ratio [HR], 4.3; 95% CI, 1.2–16.1) and HIV seroconversion (HR, 19.4; 95% CI 3.8–99.9) during the interval between tests were correlated with HSV-2 incident infection. Conclusion Offering HSV-2 serologic counseling and testing at HIV counseling and testing sites might help prevent the spread of both infectious diseases.

Evaluation of an IgM/IgG sensitive enzyme immunoassay and the utility of index values for the screening of syphilis infection in a high-risk population.

Background Serologic testing for herpes simplex virus type-2 (HSV-2) is being implemented in sexually transmitted disease (STD) clinics. Goal To determine the performance characteristics of two HSV-2 type-specific serologic assays in a public health laboratory. Study Design Sera stored from a cross-sectional study were tested with the Meridian Diagnostics and Focus Technologies HSV-2 ELISA tests and a type-specific strip immunoblot assay (Chiron Corp.) was used as the reference standard. Results Prevalence of HSV-2 infection in this sample was 44%. Compared to the reference standard, the sensitivity of the Meridian Diagnostics HSV-2 test was 95.5% (95% CI 83.3, 99.2) and specificity was 98.2% (95% CI 89.0, 99.9). The Focus Technologies test yielded 97.7% (95% CI 86.5, 99.9) sensitivity and 94.5% (95% CI 83.9, 98.6) specificity. Conclusions The performance of these HSV-2 type-specific serologic assays was adequate to support their use in high prevalence populations, such as STD clinic patients.

Use of an Acute Seroconversion Panel To Evaluate a Third-Generation Enzyme-Linked Immunoassay for Detection of Human Immunodeficiency Virus-Specific Antibodies Relative to Multiple Other Assays

Background: Increasing interest in the use of enzyme immunoassays (EIA) for syphilis screening has generated a considerable need for data on the performance of such tests. Methods: We compared the performance of 1 EIA, the TREP-SURE EIA to that of the Venereal Disease Research Laboratory (VDRL) and Treponema pallidum particle agglutination assay (TPPA) in the detection of infection with Treponema pallidum. In total, 674 specimens were tested by VDRL and EIA (356 VDRL-nonreactive and 318 VDRL-reactive). All specimens that were found to be reactive by either the VDRL or EIA were subsequently analyzed by TPPA. Results: We found that the TREP-SURE EIA was marginally less sensitive than the VDRL test for screening, but was significantly more specific. All EIA-TPPA discordant specimens were analyzed by multiple tests, including Immunoglobulin M- and G-specific Western blots and an IgM-specific EIA. Signal-to-cutoff ratios (index values) generated by the TREP-SURE EIA were also investigated. It was found that these values may be instructive regarding the interpretation of test results, as they were found to correlate strongly with the probability of positivity on a TPPA assay. Specimens that reacted positively on the EIA with very high index values were found overwhelmingly to be reactive by TPPA, perhaps obviating the need for the testing of most EIA positive specimens with a secondary treponemal test. Conclusions: An IgM/IgG sensitive EIA would be an effective alternative to VDRL for syphilis screening. Using the EIA index values may provide additional, helpful information to the diagnostic process.

Real-Time PCR for detection of herpes simplex virus without nucleic acid extraction

ABSTRACT A human immunodeficiency virus type 1 (HIV-1)/HIV-2 antibody screening assay, the Genetic Systems HIV-1/HIV-2 PLUS O EIA, was compared to several established screening or confirmatory tests using an acute HIV seroconversion panel. The HIV-1/HIV-2 PLUS O EIA showed an improved sensitivity over all tested antibody screening methods, and detected antibody in 7 of 19 specimens found to be negative by a first-generation EIA but positive for the presence of HIV RNA.