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Acute human immunodeficiency virus (HIV) infection (AHI) is a highly infectious phase of disease that lasts approximately 2 months and is characterized by nonspecific clinical symptoms.1 AHI contributes disproportionately to HIV transmission because it is associated with a high level of viremia, despite negative or indeterminate antibody (Ab) tests.2 Diagnosis of AHI with individual or pooled nucleic acid amplification tests (p-NAAT) can enable infected persons to adopt behaviors that reduce HIV transmission, facilitate partner referral for counseling and testing, and identify social networks of persons with elevated rates of HIV transmission.3 The national HIV surveillance case definition does not distinguish AHI from other stages of HIV infection,4 and the frequency of AHI among reported HIV cases is unknown. In 2008, to increase detection of AHI and demonstrate the feasibility of AHI surveillance, the New York City Department of Health and Mental Hygiene (NYC DOHMH) initiated p-NAAT screening at four sexually transmitted disease (STD) clinics and enhanced citywide HIV surveillance (using a standard case definition) to differentiate AHI among newly reported cases. Seventy cases of AHI (representing 1.9% of all 3,635 HIV diagnoses reported in New York City) were identified: 53 cases from enhanced surveillance and 17 cases from p-NAAT screening (representing 9% of 198 HIV diagnoses at the four clinics). Men who have sex with men (MSM) constituted 81% of AHI cases. Screening STD clinic patients, especially MSM, with p-NAAT can identify additional cases of HIV infection. Surveillance for AHI is feasible and can identify circumstances in which HIV prevention efforts should be intensified.
NYC DOHMH operates nine STD clinics in the five boroughs of New York City.* All clinics offer rapid HIV-Ab screening on blood specimens. In May 2008, NYC DOHMH began phasing in routine p-NAAT screening for AHI at four New York City STD clinics, beginning at Jamaica in Queens, then Chelsea in Manhattan and Fort Greene in Brooklyn in June, and finally Morrisania in the Bronx in November. Clinics were selected because of their HIV testing volume (39,000 [65%] of all HIV tests performed at New York City STD clinics in 2007) and availability of space to process the additional laboratory specimens. Testing was conducted by a commercial vendor.† Specimens from all patients whose rapid HIV-Ab test was negative were tested by polymerase chain reaction in pools of 512 specimens. If the pool was negative for HIV RNA, all component specimens were classified as “presence of HIV not detected.” If the pool was positive, component specimens were tested to identify which specimen(s) contained HIV RNA.
From May 5 to December 31, 2008, the four STD clinics performed 21,425 rapid HIV-Ab tests, of which 184 (0.9%) were HIV-Ab positive. HIV RNA was detected by p-NAAT in 17 (0.08%) of the 21,241 Ab-negative specimens. These 17 AHI cases represented 9% of 198 HIV diagnoses‡ at the four clinics during the screening period: 11 (11%) of 103 at Chelsea, one of five at Morrisania, two (5%) of 40 at Jamaica, and three (6%) of 50 at Fort Greene.
STD clinic staff members received positive p-NAAT results indicative of AHI approximately 3 weeks§ after patients had received negative rapid HIV-Ab test results. Public health advisors (PHAs) telephoned patients and asked them to return as soon as possible for follow-up testing and a more extensive interview regarding risk behaviors and symptoms. Sixteen of the 17 patients returned, most within 2 weeks of notification (range: 0-22 days). The patient who did not return was contacted and interviewed but had moved to another jurisdiction and received follow-up there.
Median age of patients with AHI was 28 years (range: 19-42 years). All 16 male patients were MSM; three reported having sex with men and women. The female patient reported commercial sex work and injection-drug use. Seroconversion was confirmed by Western blot in all 16 patients who returned. Nine patients were documented in the New York City STD registry, seven as having had previous and two as having concurrent syphilis infection. Eleven patients recalled one or more symptoms during the 4 weeks preceding receipt of their AHI diagnosis: fever (seven), malaise (six), night sweats (six), sore throat (five), joint pain (four), swollen glands (four), and headache (four). Patients reported an average of four sex partners (range: 0-16; two sex partners also were needle-sharing partners) during the 3 months before diagnosis. Of the 44 partners reported, sufficient information was provided to notify 36 (82%) of their HIV exposure, and among those, 16 (44%) reported that they were HIV-infected and were documented in the New York City HIV Surveillance Registry. Of the 20 who did not know their HIV status, 16 agreed to HIV testing, performed on the same day as notification. One partner was HIV-Ab positive. The Ab-negative patients, who also were p-NAAT negative, were encouraged to retest in 3 months.
NYC DOHMH conducts surveillance to identify new cases of HIV infection from provider reports and electronically reportable laboratory results (positive Western blot and all CD4 and HIV viral load results).∥ In follow-up, PHAs obtain demographic and risk information through chart review at the provider facility and match data to criteria in the national HIV surveillance case definition.4 In January 2008, NYC DOHMH enhanced routine HIV surveillance with a working case definition for AHI (see sidebar) to determine whether AHI was present at initial diagnosis. PHAs also documented evidence for AHI, including testing history or provider diagnosis.
Enhanced surveillance identified 53 AHI cases among the 3,482 new HIV diagnoses investigated by PHAs. Forty (75%) met the AHI case definition on the basis of laboratory criteria. Median age was 32 years (range: 15-62 years) among 50 men and three women. Among the 50 men, 41 (82%) reported having sex with men. Among the 53 AHI cases, 23 (43%) were diagnosed at hospitals, 17 (32%) at private physician offices, 12 (23%) at community clinics, and one (2%) at a college clinic; each of 35 health-care providers diagnosed 1-10 cases.
Of the 3,635 new HIV diagnoses in 2008 reported to NYC DOHMH by March 15, 2009, AHI was present in 70 (1.9%), including the 17 diagnosed by p-NAAT, at the time of their HIV diagnosis. Sixty-six (94%) patients with AHI were male, and 57 (81%) were MSM. By comparison, 2,726 (75%) of all new HIV diagnoses reported in NYC in 2008 were in males, including 1,580 (43%) in MSM.
CW Shepard, MD, K Gallagher, MPH, SD Bodach, MPH, A Kowalski, MPH, AS Terzian, PhD, E Begier, MD, I Weisfuse, MD, New York City Dept of Health and Mental Hygiene. S Blank, MD, Div of Sexually Transmitted Diseases Prevention; BM Branson, MD, Div of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC.
The findings in this report confirm that p-NAAT can increase AHI diagnoses among high-risk STD clinic patients,3,5,6 and indicate that AHI diagnoses can be made apart from p-NAAT screening programs. The 70 AHI cases identified by NYC DOHMH represent a fraction of the 4,762 (72 per 100,000 population) new infections previously estimated to occur annually in New York City,7 highlighting the need to improve awareness and detection of AHI. Notably, 81% of AHI cases identified in New York City were among MSM, reflecting the high HIV incidence in MSM7 and demonstrating the risk for missed diagnoses when HIV-Ab testing alone is used in a high-risk, high-incidence population.5 Without p-NAAT screening, 9% of the HIV infections documented by the four STD clinics during the screening period would have been missed. However, because HIV RNA is not detectable for approximately 10 days after infection,8 even NAAT will not identify all infected persons. CDC recommends that persons with very recent high-risk exposures be encouraged to retest after 4-6 weeks, even if p-NAAT is negative.
Based on the results, NYC DOHMH has expanded p-NAAT screening to all nine New York City STD clinics and improved ascertainment of AHI in routine surveillance. As of June 26, 2009, reportable laboratory results that might indicate recent viral acquisition are flagged systematically as potential AHI cases before investigation. Because AHI is associated with high levels of HIV RNA,9 an HIV RNA measurement >100,000 copies/mL for a person not previously reported to the health department will prompt PHAs to query the ordering provider about possible AHI. The health department also plans to include AHI data in routine surveillance reports it distributes and has sent letters asking that providers consider AHI in patients who have a negative HIV-Ab test and a high HIV viral load and document AHI diagnoses in patient charts.
The findings in this report are subject to at least three limitations. First, STD clinics were not selected for p-NAAT screening based on demographic or behavioral characteristics of their patients. Targeted screening, particularly for MSM, can improve the yield of p-NAAT screening.6 The majority of AHI cases were found at the Chelsea STD clinic, which served approximately one third of patients identified as MSM at New York City STD clinics in 2007. Thus, the yield of the New York City p-NAAT screening program might be lower in clinics serving fewer MSM. Second, the findings are subject to testing bias. The New York City STD clinics used a rapid HIV-Ab test that is less sensitive during the first 3 weeks after acquisition of HIV than conventional Ab tests.5 Use of a test with a longer Ab-negative window increases the apparent yield of p-NAAT screening, because more specimens are negative for HIV antibodies and subsequently tested by p-NAAT. Finally, cases of AHI might have been misclassified or not detected. The AHI case definition allowed for provider diagnosis only, which might have resulted in misclassification among the 13 (25%) cases that met the case definition on this criterion alone. Reportable laboratory events in the case definition might not have been reported in full or accurately to NYC DOHMH. The laboratory criteria in the case definition also included nonreportable laboratory events, such as enzyme immunoassay (EIA) and negative Western blot results, that might not have been available or ascertained during chart review. Lack of documentation of a recent negative test might have resulted in undercounting of AHI.
In the United States, NAAT is the only option available for detecting AHI before seroconversion. Ab-negative specimens are pooled to reduce costs, but p-NAAT testing increases the expense of HIV screening and the turnaround time for test results. Alternatives to detect AHI soon might be available. Combination assays that use an EIA technique for p24 antigen and HIV Ab can detect HIV infection within 3-5 days of first detection by NAAT.10 Such tests can make routine screening for AHI more feasible and potentially less expensive by detecting almost all acute HIV infections with a single screening test. Confirmatory testing with both an Ab test and RNA test after a reactive combination test result could then distinguish AHI or longstanding HIV infection. These combination tests have been available in Europe and elsewhere since 2002, and several manufacturers have indicated their intention to seek Food and Drug Administration approval for use in the United States (CDC, personal communication, 2009). Wider use of p-NAAT and combination assays could increase AHI identification. CDC is considering a national AHI case definition for use in national HIV surveillance to identify areas or populations in which HIV infection is spreading, and for assessing new methods for AHI screening.
This report is based, in part, on contributions from NYC DOHMH staff members involved in AHI screening, surveillance, and response.
Not previously reported as an HIV case to the New York City HIV Surveillance Registry
AND one of the following (A, B, or C):
A) A negative Western blot (WB), indeterminate WB, or negative screening test for HIV antibody (e.g., enzyme immunoassay or rapid test) AND an HIV viral load of >5,000 copies/mL measured from a specimen drawn within 1 month of the specimen that provided the negative WB, indeterminate WB, or negative screening test for HIV.
B) Serial (all within 1 month) HIV antibody tests consistent with a recent HIV infection (e.g., an indeterminate WB followed by a positive WB, a negative WB followed by a positive WB, or a negative screening test, such as enzyme immunoassay, for HIV antibody, followed by a positive WB).
C) Physician-documented diagnosis of “acute HIV” or “primary HIV.”
What is already known on this topic?
Acute human immunodeficiency virus (HIV) infection (AHI) is a short, highly infectious phase of disease that can be detected by screening antibody-negative specimens with pooled nucleic acid amplification tests (p-NAAT). However, because most HIV screening is conducted only with antibody tests, only a small proportion of HIV infections are diagnosed during the acute phase.
What is added by this report?
In 2008, p-NAAT screening at four sexually transmitted disease (STD) clinics in New York City detected 17 cases of AHI: 16 were among men who have sex with men (MSM), and nine were in patients who had a history of previous or concurrent syphilis. Citywide surveillance identified 53 cases of AHI, of which 77% were in MSM. AHI represented 9% of all HIV diagnoses at the four STD clinics, but only 1.9% of the 3,635 HIV diagnoses reported in New York City during 2008 and 1.5% of the 4,762 new HIV infections estimated to have occurred.
What are the implications for public health practice?
Screening for AHI, particularly among MSM, can pinpoint circumstances in which new HIV infections are occurring and identify highly infectious persons who, with their partners, require concentrated efforts to prevent further transmission. Intensive risk reduction interventions should focus on MSM, especially those with syphilis.
*Bronx, Brooklyn, Manhattan, Queens, and Staten Island.
†Additional information regarding the procedure used is available at http://www.ngi.com/services/screening.asp. Protocols and validation data for use of this polymerase chain reaction technique for patient diagnosis were submitted and approved by the New York State Clinical Laboratory Evaluation Program.
‡Three patients tested twice with Ab-positive results each time.
§Results for negative pools are returned to NYC DOHMH in 10-12 business days. Results from deconstruction and individual testing of a positive pool take an additional 3-5 days. Thus, a positive result of p-NAAT would take 15-20 days from specimen collection until patient notification. Conversely, the results of conventional confirmatory testing after a reactive rapid test are returned to NYC DOHMH within 7-10 business days, and the patients who are rapid-test positive are instructed to return in 10 days to receive the results of confirmatory testing.
∥Since 2005, CD4 results (even if in the normal range) and HIV viral loads (even if undetectable) have been reportable in New York state.
Acute HIV Infection—New York City, 2008. JAMA. 2010;303(8):725–727. doi:
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