Jeffrey D. Klausner

Impact of Highly Active Antiretroviral Treatment on HIV Seroincidence Among Men Who Have Sex With Men: San Francisco

OBJECTIVES This study assessed the countervailing effects on HIV incidence of highly active antiretroviral treatment (HAART) among San Francisco men who have sex with men (MSM). METHODS Behavioral risk was determined on the basis of responses to cross-sectional community interviews. HIV incidence was assessed through application of an enzyme-linked immunoassay testing strategy. RESULTS Use of HAART among MSM living with AIDS increased from 4% in 1995 to 54% in 1999. The percentage of MSM who reported both unprotected anal intercourse and multiple sexual partners increased from 24% in 1994 to 45% in 1999. The annual HIV incidence rate increased from 2.1% in 1996 to 4.2% in 1999 among MSM who sought anonymous HIV testing, and the rate was high (5.3%) but stable in a blinded survey of MSM seeking sexually transmitted disease services. CONCLUSIONS Any decrease in per contact risk of HIV transmission due to HAART use appears to have been counterbalanced or overwhelmed by increases in the number of unsafe sexual episodes.

Prevalence of Rectal, Urethral, and Pharyngeal Chlamydia and Gonorrhea Detected in 2 Clinical Settings among Men Who Have Sex with Men: San Francisco, California, 2003

BACKGROUND The Centers for Disease Control and Prevention developed screening and diagnostic testing guidelines for chlamydia and gonorrhea at urethral, rectal, and pharyngeal sites for men who have sex with men (MSM). However, in most clinical settings, rectal chlamydial testing is not performed for MSM, and primarily sexually transmitted disease (STD) clinics alone perform routine rectal and pharyngeal gonorrhea screening for asymptomatic men. METHODS We evaluated the prevalence of rectal, urethral, and pharyngeal chlamydial and gonococcal infections among MSM seen at the municipal STD clinic and the gay mens community health center. We also determined the proportion of asymptomatic rectal infections, described the patterns of single and multiple anatomic sites of infection, and evaluated the proportion of chlamydial infections that would be missed and not treated if MSM were not routinely tested for chlamydia. We tested specimens using previously validated nucleic acid amplification tests (NAATs). RESULTS The prevalence of infection varied by anatomic site (chlamydia: rectal, 7.9%; urethral, 5.2%; and pharyngeal, 1.4%; for gonorrhea, rectal, 6.9%; urethral, 6.0%; and pharyngeal, 9.2%). Approximately 85% of rectal infections were asymptomatic supporting the need for routine screening. Because 53% of chlamydial infections and 64% of gonococcal infections were at nonurethral sites, these infections would be missed and not treated if only urethral screening was performed. In addition, >70% of chlamydial infections would be missed and not treated if MSM were tested only for gonorrhea. CONCLUSIONS Because these infections enhance both HIV transmission and susceptibility, clinical settings serving MSM should evaluate the prevalence of chlamydial and gonococcal infections by anatomic site using validated NAATs.

Syphilis increases HIV viral load and decreases CD4 cell counts in HIV-infected patients with new syphilis infections.

Background: Syphilitic ulcers are known to facilitate the transmission of HIV infection, but the effect of syphilis infection on HIV viral loads and CD4 cell counts is poorly understood. Methods: We abstracted medical records for HIV-infected male syphilis patients seen at three clinics in San Francisco and Los Angeles from January 2001 to April 2003. We compared plasma HIV-RNA levels and CD4 cell counts during syphilis infection with those before syphilis infection and after syphilis treatment, using the Wilcoxon signed rank test. Results: Fifty-two HIV-infected men with primary or secondary syphilis had HIV viral load and CD4 cell count data available for analysis; 30 (58%) were receiving antiretroviral therapy. Viral loads were higher during syphilis compared with pre-syphilis levels by a mean of 0.22 RNA log10 copies/ml (P = 0.02) and were lower by a mean of −0.10 RNA log10 copies/ml (P = 0.52) after syphilis treatment. CD4 cell counts were lower during syphilis infection than before by a mean of −62 cells/mm3 (P = 0.04), and were higher by a mean of 33 cells/mm3 (P = 0.23) after syphilis treatment. Increases in the HIV viral load and reductions in the CD4 cell count were most substantial in men with secondary syphilis and those not receiving antiretroviral therapy. Conclusion: Syphilis infection was associated with significant increases in the HIV viral load and significant decreases in the CD4 cell count. The findings underscore the importance of preventing and promptly treating syphilis in HIV-infected individuals.

Syphilis and HIV Infection: An Update

The striking increase in the prevalence of concordant human immunodeficiency virus (HIV) infection and syphilis observed by clinicians and public health officers over the past decade has renewed interest in the subject. Although the effect of HIV infection on the natural history of syphilis has been known for a long time, it was not until recently that several studies documented that syphilis may also impact the course of HIV infection. Despite an improved understanding of the interaction of these 2 conditions, many controversies still exist. In this article, we focus on the most recent literature describing the epidemiology, clinical manifestations, and treatment of syphilis in the context of HIV infection.

Nucleic acid amplification tests in the diagnosis of chlamydial and gonococcal infections of the oropharynx and rectum in men who have sex with men.

Background: Several nucleic acid amplification tests (NAATs) are US Food and Drug Administration-cleared for detecting urogenital Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infection, but they have not been adequately evaluated for the relatively common oropharyngeal or rectal CT and GC infections in men who have sex with men (MSM). Methods: Multiple swabs were collected from the oropharynx and rectum of MSM attending a city sexually transmitted disease clinic. The specimens were tested by standard culture and the following NAATs: Roches Amplicor (PCR), Becton Dickinsons ProbeTec (SDA), and Gen-Probes APTIMA Combo 2 (AC2) for the detection of CT and GC. Confirmatory testing of specimens with discrepant results was done by NAATs using alternate primers. Results: A total of 1110 MSM were enrolled. Based on initial findings on 205 MSM, PCR had a 78.9% GC specificity with oropharyngeal swabs. Thus, we discontinued PCR testing for the rest of the study. For oropharyngeal GC (89 infections detected), sensitivities were 41% for culture, 72% for SDA, and 84% for AC2. For rectal GC (88 infections detected), sensitivities were 43% for culture, 78% for SDA and 93% for AC2. For oropharyngeal CT (9 infections detected), sensitivities were 44% for culture, 67% for SDA, and 100% for AC2. For rectal CT (68 infections detected), sensitivities were 27% for culture, 63% for SDA, and 93% for AC2. Specificities of SDA and AC2 were ≥99.4% for both organisms and anatomical sites. Conclusions: AC2 and SDA were far superior to culture for the detection of CT or GC from the oropharynx and rectum with AC2 detecting twice as many infections as culture. Further analyses with larger pharyngeal samples are needed, but clearly NAATs can improve our ability to diagnose rectal and oropharyngeal infection with CT or GC in MSM.

Increases in sexually transmitted infections and sexual risk behaviour without a concurrent increase in HIV incidence among men who have sex with men in San Francisco: a suggestion of HIV serosorting?

Background: Sexually transmitted infections (STI) and unprotected anal intercourse (UAI) have been increasing among men who have sex with men (MSM) in San Francisco. However, HIV incidence has stabilised. Objectives: To describe recent trends in sexual risk behaviour, STI, and HIV incidence among MSM in San Francisco and to assess whether increases in HIV serosorting (that is, selective unprotected sex with partners of the same HIV status) may contribute to preventing further expansion of the epidemic. Methods: The study applies an ecological approach and follows the principles of second generation HIV surveillance. Temporal trends in biological and behavioural measures among MSM were assessed using multiple pre-existing data sources: STI case reporting, prevention outreach programmatic data, and voluntary HIV counselling and testing data. Results: Reported STI cases among MSM rose from 1998 through 2004, although the rate of increase slowed between 2002 and 2004. Rectal gonorrhoea cases increased from 157 to 389 while early syphilis increased from nine to 492. UAI increased overall from 1998 to 2004 (p<0.001) in community based surveys; however, UAI with partners of unknown HIV serostatus decreased overall (p<0.001) among HIV negative MSM, and among HIV positive MSM it declined from 30.7% in 2001 to a low of 21.0% in 2004 (p<0.001). Any UAI, receptive UAI, and insertive UAI with a known HIV positive partner decreased overall from 1998 to 2004 (p<0.001) among MSM seeking anonymous HIV testing and at the STI clinic testing programme. HIV incidence using the serological testing algorithm for recent HIV seroconversion (STARHS) peaked in 1999 at 4.1% at the anonymous testing sites and 4.8% at the STI clinic voluntary testing programme, with rates levelling off through 2004. Conclusions: HIV incidence among MSM appears to have stabilised at a plateau following several years of resurgence. Increases in the selection of sexual partners of concordant HIV serostatus may be contributing to the stabilisation of the epidemic. However, current incidence rates of STI and HIV remain high. Moreover, a strategy of risk reduction by HIV serosorting can be severely limited by imperfect knowledge of one’s own and one’s partners’ serostatus.

Reassessing HIV prevention

The largest investments in AIDS prevention targeted to the general population are being made in interventions where the evidence for large-scale impact is uncertain.

Rectal gonorrhea and chlamydia reinfection is associated with increased risk of HIV seroconversion.

Introduction:HIV infection continues to disproportionately affect men who have sex with men (MSM). Identification of modifiable risk factors for HIV infection among MSM is critical for effective prevention. Methods:We examined the relationship between number of prior rectal Neisseria gonorrhoeae (GC) or Chlamydia trachomatis (CT) infections and HIV seroconversion in a retrospective cohort of HIV-uninfected MSM diagnosed with a rectal infection. Number of rectal CT or GC infections in the prior 2 years was the primary exposure. Univariate and multivariate Cox proportional hazards models were used to estimate the association between prior rectal infections and HIV seroconversion. Results:A total of 541 MSM were observed for a total of 1197.96 person-years. Overall, 27 (4.99%) of the MSM became infected with HIV, for an estimated annual incidence of 2.25% [95% confidence interval (CI): 1.49 to 3.26]. In multivariate analysis, an early syphilis diagnosis in the past 2 years (hazard ratio = 4.04, 95% CI: 1.19 to 13.79) and 2 prior CT or GC rectal infections in the past 2 years (hazard ratio = 8.85, 95% CI: 2.57 to 30.40) were associated with incident HIV. Conclusions:Among MSM infected with rectal GC or CT, a history of 2 additional prior rectal infections was associated with an 8-fold increased risk of HIV infection. HIV-uninfected MSM with multiple rectal infections represent a population in need of innovative HIV-prevention interventions.

Effect of highly active antiretroviral therapy on diagnoses of sexually transmitted diseases in people with AIDS

BACKGROUND There has been an increase in high-risk sexual behaviour and sexually transmitted diseases (STD) during the time period when highly active antiretroviral therapy (HAART) became widely available. We examined whether taking HAART increased the risk of acquiring an STD--an epidemiological marker of unsafe sex--in people with AIDS. METHODS We did a computerised match of people in the San Francisco STD and AIDS registries. People with AIDS who were diagnosed before 1999 and alive in November, 1995, or later, were classified as having had an STD after AIDS diagnosis or not having had an STD after AIDS diagnosis. We used a Cox proportional hazards model to see whether use of antiretroviral therapy was associated with acquiring an STD after AIDS, after adjustment for sex, age, race, HIV-1 risk category, and CD4 count at AIDS diagnosis. FINDINGS People with AIDS who had had HAART showed an independent increase in the risk of developing an STD (hazard ratio 4.10; 95% CI 2.84-5.94). Americans of African origin, younger age, and higher CD4 count at AIDS diagnosis were also associated with acquiring an STD after AIDS. The number of people living with AIDS who acquired an STD increased over time from 60 (0.66%) in 1995 to 113 (1.32%) in 1998 (p<0.001). INTERPRETATION We have shown that people on HAART are more likely to develop an STD, an epidemiological marker of unsafe sex. More intensive risk-reduction counselling and STD screening for people with AIDS is needed.

Male circumcision, religion, and infectious diseases: an ecologic analysis of 118 developing countries.

BackgroundBoth religious practices and male circumcision (MC) have been associated with HIV and other sexually-transmitted infectious diseases. Most studies have been limited in size and have not adequately controlled for religion, so these relationships remain unclear.MethodsWe evaluated relationships between MC prevalence, Muslim and Christian religion, and 7 infectious diseases using country-specific data among 118 developing countries. We used multivariate linear regression to describe associations between MC and cervical cancer incidence, and between MC and HIV prevalence among countries with primarily sexual HIV transmission.ResultsFifty-three, 14, and 51 developing countries had a high (>80%), intermediate (20–80%), and low (<20%) MC prevalence, respectively. In univariate analyses, MC was associated with lower HIV prevalence and lower cervical cancer incidence, but not with HSV-2, syphilis, nor, as expected, with Hepatitis C, tuberculosis, or malaria. In multivariate analysis after stratifying the countries by religious groups, each categorical increase of MC prevalence was associated with a 3.65/100,000 women (95% CI 0.54-6.76, p = 0.02) decrease in annual cervical cancer incidence, and a 1.84-fold (95% CI 1.36-2.48, p < 0.001) decrease in the adult HIV prevalence among sub-Saharan African countries. In separate multivariate analyses among non-sub-Saharan African countries controlling for religion, higher MC prevalence was associated with a 8.94-fold (95% CI 4.30-18.60) decrease in the adult HIV prevalence among countries with primarily heterosexual HIV transmission, but not, as expected, among countries with primarily homosexual or injection drug use HIV transmission (p = 0.35).ConclusionMale circumcision was significantly associated with lower cervical cancer incidence and lower HIV prevalence in sub-Saharan Africa, independent of Muslim and Christian religion. As predicted, male circumcision was also strongly associated with lower HIV prevalence among countries with primarily heterosexual HIV transmission, but not among countries with primarily homosexual or injection drug use HIV transmission. These findings strengthen the reported biological link between MC and some sexually transmitted infectious diseases, including HIV and cervical cancer.