Sexually transmitted infections (STIS) have a well-established synergistic relationship with HIV infection. Coinfection with HIV and an STI can increase the probability of HIV transmission to an uninfected partner by increasing HIV concentrations in genital lesions, genital secretions, or both.1,2 STI infection can also increase the likelihood of HIV acquisition by interrupting mucosal barriers, increasing the access to and concentration of HIV receptor cells, and, in women, changing the vaginal microflora to favor HIV infection.3–6 Among patients with acute HIV (AHI), the 4- to 6-week interval in the HIV disease course when the virus can be detected in the blood before seroconversion, coinfection with an STI may be common.7 More than 70% of AHI patients had an STI coinfection in a Malawian sexually transmitted disease (STD) clinic in 2 separate studies.8,9 However, little is known about the frequency of STI and acute HIV coinfection outside of the STD clinic setting.
To further examine this issue, we conducted a secondary data analysis of AHI patients identified by the Screening and Tracing Active Transmission Program (STAT) of the North Carolina (NC) Department of Health and Human Services and the University of North Carolina at Chapel Hill (UNC). Our goal was to describe the prevalence and predictors of acute HIV and STI coinfection in a systematically collected, statewide sample of AHI patients.
The STAT screening methodology has been previously described.10,11 In brief, clients presenting for confidential HIV CTS at approximately 135 publicly funded sites in NC are included in a testing algorithm to detect acute HIV infection. Serum samples submitted for HIV testing are first tested for HIV-1 antibody, and then all antibody negative samples are screened for HIV-1 RNA by pooling.10 Antibody indeterminate samples are tested for HIV RNA individually. Samples in which HIV-1 RNA is detected and are either enzyme immunoassay (EIA) negative or EIA positive and Western Blot negative or indeterminate represent acute infections, and are confirmed by follow-up antibody testing. Serum HIV-1 RNA is quantified with an HIV-1 reverse transcriptase polymerase chain reaction assay (Amplicor HIV-1 Monitor Test, version 1.5, Roche Diagnostics). We included 75 clients with AHI identified from November 1, 2002 to October 31, 2006.
The NC Department of Health and Human Services assigns potential AHI cases to a team of disease intervention specialists who perform initial interviews, confirmatory testing, and referrals to care within 72 hours of notification.11 After interview with the patient and medical record review(s), disease intervention specialists complete standardized case report forms. Patients with AHI who presented for confidential HIV testing signed informed consent forms authorizing the collection of personal information and release of information and blood to the STAT program. This study was approved by the UNC Institutional Review Board.
We defined STI coinfection as the diagnosis of gonorrhea, chlamydia, trichomoniasis, human papillomavirus, genital herpes, bacterial vaginosis, or syphilis during the same month and year of the AHI diagnosis. STI infections were confirmed by medical record review. We considered appropriate symptoms reported during an 8-week window period (±4 weeks of the test date, inclusive) to be acute retroviral syndrome. To determine factors associated with STI coinfection, we computed the prevalence of coinfection, prevalence ratios (PR), and 95% exact CIs. We examined variations in mean log10 (HIV-1 RNA) with 1-way analyses of variance.12 All analyses were performed with SAS Software (version 9.1.2, SAS Institute, Cary, NC).
From November 1, 2002 to October 31, 2006, 79 persons with AHI were detected through the STAT program. Of these, 3 could not be located and 1 refused posttest counseling and partner notification services, leaving a sample of 75 patients with AHI for analysis. Seventy-five percent were men and 52% were men who have sex with men (MSM). The median age was 28 years (range: 16-56). The majority of the population were Black, followed by a quarter white, non-Hispanic. Half of the cases were identified at STD clinics. A majority of persons (n = 45, 60%) reported at least 1 acute retroviral symptom at or before the initial testing date, most commonly, fever (37%), night sweats (24%), fatigue (24%), body aches (21%), and nausea (21%).
Nearly one-third of patients (n = 23, 31%) had an STI at or near the time of the AHI diagnosis, consistent with coinfection (Table 1). The most common coinfections were gonorrhea (39%), trichomoniasis (22%), and syphilis (17.4%) although they differed substantially by gender—the majority of male coinfections were gonorrhea (54%), whereas among women the most common coinfection was trichomoniasis (50%, Fisher’s exact test, P < 0.01).
We identified an interrelationship between gender, race, risk category, and STI coinfection. The prevalence of coinfection was lower in MSM (18%, PR = 0.34, 95% CI: 0.15, 0.76) and heterosexual men (35%, PR = 0.67, 95% CI: 0.31, 1.45) than women (53%, Table 2). Nonwhites were 3.9 times as likely to report a coinfection as whites (95% CI: 1.00, 15.10). Among MSM, all 7 STI coinfections occurred in nonwhites (P = 0.03); this finding was consistent for heterosexual men as all 6 coinfections were in nonwhites, although only 1 white heterosexual man was in the study population. Among women, 2 of the 3 white women were coinfected and half (8 of 16) of the nonwhite women reported an STI coinfection.
The prevalence of STI coinfection was roughly equal among AHI patients detected at HIV counseling and testing (CTS) locations and STD testing locations. The overall mean serum viral load at the time of testing was 5.2 log10 copies/mL, and we found little variation by demographic or risk factors.
The proportion of AHI patients with STI coinfections is surprising as our study was not limited to the STD clinic setting. Although about half of the AHI cases were identified in STD clinics where STI screening is routine, the proportion with coinfections from STD clinics (35%) was roughly the same as those cases identified from HIV CTS sites (36%), where STI screening is less frequent and likely restricted to urine-based nucleic-acid amplification testing for gonorrhea and chlamydia, if it is conducted at all. Although the coding of testing site type is variable from county to county and therefore subject to misclassification, our results underscore the importance of STI symptoms as an indicator of AHI risk, even in non-STD clinic settings. Further, high rates of STIs near the time of HIV transmission in NC may suggest the importance of STIs on HIV transmission in the southeastern United States, a region that has been disproportionately impacted by HIV and STIs.13–17
The variation in STI coinfection prevalence of STI coinfection by gender, risk category, and race is compelling. MSM in our study were less likely to have a coinfection (18%) than heterosexual men (35%) or women (53%), and almost all (91%) coinfections occurred in nonwhites. These findings may reflect the epidemiology of the NC HIV epidemic where racial disparities are dramatic—the HIV rate for non-Hispanic blacks is more than 8 times greater than for non-Hispanic whites—and heterosexual transmission is nearly as prominent as MSM transmission.13,18 Heterosexual transmission of HIV in NC occurs largely among blacks; high rates of STIs in this group would facilitate HIV transmission and may be a necessary component of the HIV epidemic for this population.18 Although we have likely underestimated the number of coinfections as not all cases are uniformly screened for STIs, this bias may be most dramatic for MSM as pharyngeal and rectal cultures for gonorrhea are only collected based on a risk assessment at STD clinics.
Our study has several noteworthy limitations. Our sample size is small and does not represent all HIV cases identified in NC. The STAT program routinely tests for HIV RNA in all samples from publicly funded clinics but approximately 60% of NC HIV cases are detected outside of the public testing system. If people who test through the publicly funded system are systematically different than those who test outside of the publicly funded system, selection bias may be introduced. In addition, STI screening practices and diagnostic methods vary throughout the state; however, we would expect this to result in an underestimate of STI coinfections. As we have defined them, STI coinfections can represent prevalent infections acquired before HIV infection, cotransmission events, or incident infections acquired after HIV infection. Finally, our modest sample size results in limited power to detect small differences and a decreased ability to control confounding in multivariable models.
The detection of AHI affords a tremendous public health opportunity to interrupt transmission and detect networks at high risk, but recognition requires a unique synergy of clinical suspicion, risk awareness, and appropriate diagnostic tests. Although people with primary infection often present to medical care, the opportunity for diagnosis is frequently missed either by not recognizing acute retroviral syndrome or reliance on antibody testing alone.19–22 Patients who coacquire HIV and an STI infection may be missed by standard HIV antibody tests when STI symptoms appear, given the short incubation periods of some bacterial STIs. This is an important limitation of strategies to offer HIV testing services to all STI patients, as acute HIV infection will often be missed in settings where testing is limited to standard third-generation EIAs.
1. Cohen MS, Hoffman IF, Royce RA, et al; AIDSCAP Malawi Research Group. Reduction of concentration of HIV-1 in semen after treatment of urethritis: Implications for prevention of sexual transmission of HIV-1. Lancet 1997; 349:1868–1873.
2. Gray RH, Wawer MJ, Brookmeyer R, et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet 2001; 357:1149–1153.
3. Reynolds SJ, Risbud AR, Shepherd ME, et al. Recent herpes simplex virus type 2 infection and the risk of human immunodeficiency virus type 1 acquisition in India. J Infect Dis 2003; 187:1513–1521.
4. Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: A meta-analysis. J Infect Dis 2002; 185:45–52.
5. Cohen MS. HIV and sexually transmitted diseases: Lethal synergy. Top HIV Med 2004; 12:104–107.
6. Galvin SR, Cohen MS. The role of sexually transmitted diseases in HIV transmission. Nat Rev 2004; 2:33–42.
7. Stekler J, Collier AC. Primary HIV Infection. Curr HIV/AIDS Rep 2004; 1:68–73.
8. Pilcher CD, Price MA, Hoffman IF, et al. Frequent detection of acute primary HIV infection in men in Malawi. AIDS 2004; 18:517–524.
9. Pilcher CD, Joaki G, Hoffman IF, et al. Amplified transmission of HIV-1: Comparison of HIV-1 concentrations in semen and blood during acute and chronic infection. AIDS 2007; 21:1723–1730.
10. Pilcher CD, McPherson JT, Leone PA, et al. Real-time, universal screening for acute HIV infection in a routine HIV counseling and testing population. JAMA 2002; 288:216–221.
11. Pilcher CD, Fiscus SA, Nguyen TQ, et al. Detection of acute infections during HIV testing in North Carolina. N Eng J Med 2005; 352:1873–1883.
12. Quinn TC, Wawer MJ, Sewankambo N, et al; Rakai Project Study Group. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med 2000; 342:921–929.
13. Centers for Disease Control and Prevention. Cases of HIV infection and AIDS. In: The United States and Dependent Areas, 2005. Vol. 17, HIV/AIDS Surveillance Report. Atlanta, GA: CDC, 2006.
14. Qian HZ, Taylor RD, Fawal HJ, et al. Increasing AIDS case reports in the South: US trends from 1981-2004. AIDS Care 2006; 18(suppl 1):S6–S9.
15. Reif S, Geonnotti KL, Whetten K. HIV Infection and AIDS in the deep south. Am J Public Health 2006; 96:970–973.
16. Whetten K, Reif S. Overview: HIV/AIDS in the deep south region of the United States. AIDS Care 2006; 18(suppl 1):S1–S5.
17. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2005. Atlanta, GA: US Department of Health and Human Services, 2006.
18. NC Department of Health and Human Services. Scope of the HIV/AIDS Epidemic in North Carolina. North Carolina Epidemiologic Profile for HIV/STD Prevention and Care Planning, July 2007.
19. Pincus JM, Crosby SS, Losina E, et al. Acute human immunodeficiency virus infection in patients presenting to an urban urgent care center. Clin Infect Dis 2003; 37:1699–1704.
20. Hightow L, MacDonald, P, Boland, et al. Missed Opportunities for the diagnosis of acute HIV infection: Room for Improvement. In: 12th Conference on Retroviruses and Opportunistic Infections; 2005; Boston, MA.
21. Clark SJ, Kelen GD, Henrard DR, et al. Unsuspected primary human immunodeficiency virus type 1 infection in seronegative emergency department patients. J Infect Dis 1994; 170:194–197.
22. Schacker T, Collier AC, Hughes J, et al. Clinical and epidemiologic features of primary HIV infection. Ann Int Med 1996; 125:257–264.