Stephen R. Tabet

HIV-1 sexually transmitted infections and sexual behavior trends among men who have sex with men in Lima Peru.

Objective:To assess and estimate trends in HIV, sexually transmitted infections (STIs), and sexual behavior among men who have sex with men (MSM) in Lima, Peru. Design:Second-generation HIV sentinel surveillance surveys conducted in 1996, 1998, 2000, and 2002. Methods:Adult men reporting sex with at least 1 man during the previous year were eligible to participate. Sexual behavior and serum HIV-1 and syphilis antibodies were assessed. HIV seroincidence was estimated by a sensitive/less-sensitive enzyme immunoassay strategy. Rectal and pharyngeal swabs for Neisseria gonorrhoeae culture and a first-void urine sample for urethral leukocytes for presumptive diagnosis of urethritis were obtained. Herpes simplex virus 2 (HSV-2) antibodies were measured in 2002. Results:Although HIV prevalence increased from 18.5% to 22.3% from 1996 through 2002, bacterial prevalence declined significantly for syphilis (16.0% to 12.4%), early syphilis (8.6% to 3.4%), and rectal gonorrhea (5.1% to 0.2%). High HIV seroincidence was estimated, with the lowest (4.8%) incidence in 1998. In 2002, HSV-2 seroprevalence was 51.0%. After adjustment for age, education, and self-reported sexual identity, our data suggest that a yearly increase by 6% in the prevalence of HIV occurred among MSM in Lima, with a corresponding decline in syphilis (by 9%), early syphilis (by 18%), and rectal gonorrhea (by 64%). Condom use during last sexual intercourse increased by 26% each year with the most recent male steady partner and, among non-sex workers, by 11% with the most recent casual partner. Conclusions:HIV continued to spread among MSM in Lima even when a decline in bacterial STIs and increase in condom use were estimated to occur. Intensification of medical and behavior prevention interventions is warranted for MSM in Peru.

Safety and toxicity of nonoxynol-9 gel as a rectal microbicide.

BACKGROUND AND OBJECTIVES Methods of HIV and STD prevention, which can be controlled by the receptive partner, are a high priority for research and development. Studies on the safety of Nonoxynol-9 (N-9) on the vaginal mucosa have yielded conflicting results. No Phase I study has evaluated the effect of N-9 on the rectal mucosa. GOALS To assess the safety of 52.5 mg of N-9 in a 1.5-g gel when applied one to four applicators per day to the rectum and penis. STUDY DESIGN The study included 25 HIV-negative and 10 HIV-positive, monogamous gay male couples in which each partner was exclusively insertive or receptive while using N-9 gel. Each participant served as his own control during placebo gel use compared to during N-9 gel use. Receptive partners underwent anoscopic examination after 1 week of placebo use and after 2, 5, and 6 weeks of N-9 gel use, with rectal biopsies obtained after 1 week of placebo use and after 5 and 6 weeks of N-9 gel use. Insertive partners had safety monitoring after 1 week of placebo use and after 2, 5, and 6 weeks of N-9. RESULTS No rectal ulcers were detected; superficial rectal erosions were noted in two HIV-negative participants. Abnormal or slightly abnormal histologic abnormalities of rectal biopsies were detected in 31 (89%) receptive participants after N-9 gel use compared to 24 (69%) participants after 1 week of placebo gel use. Meatal ulceration, not caused by herpes simplex virus, was detected in one HIV-negative participant. CONCLUSION Low-dose N-9 gel was not associated with macroscopic rectal and penile epithelial disruption or inflammation, but histologic abnormalities were commonly observed during N-9 gel as well as during placebo gel use.

Correlates of Prevalent and Incident Kaposi's Sarcoma—Associated Herpesvirus Infection in Men Who Have Sex with Men

Infection with Kaposis sarcoma-associated herpesvirus (KSHV) is common among men who have sex with men (MSM). To determine correlates of infection, 578 human immunodeficiency virus (HIV)-negative MSM were assessed by serologic assays, questionnaires, and physical examinations. At baseline, 76 (16%) of 474 participants were KSHV seropositive. Prevalent KSHV infection was significantly associated with hepatitis A (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.5-7.5), hepatitis B seropositivity (OR, 2.6; 95% CI, 1.4-4.8), herpes simplex virus (HSV)-2 (OR, 2.4; 95% CI, 1.3-4.4), and >4 male partners in the previous 6 months (OR, 1.9; 95% CI, 1.1-3.2). Fifteen KSHV seroconversions (4%) were observed for an incidence of 3.8/100 person-years, similar to HSV-1 incidence in this cohort and more frequent than incidence of HIV and HSV-2. Reporting > or =1 HIV-positive partner (OR, 5.9; 95% CI, 1.8-19.3), amyl nitrite use (OR, 7.0; 95% CI, 2.1-23.0), and lymphadenopathy in the past 6 months (OR, 7.7; 95% CI, 1.9-31.0) correlated with KSHV seroconversion.

Incidence of HIV and sexually transmitted diseases (STD) in a cohort of HIV-negative men who have sex with men (MSM).

Objective:To determine the prevalence of sexually transmited diseases (STD) and incidence of and risk factors for STD, including HIV-1, among a cohort of HIV-negative men who have sex with men (MSM). Setting:Seattle, Washington, United States. Participants:Prospective cohort of 578 HIV-negative MSM in which risk factors for acquiring a STD over 12 months follow-up were evaluated using a cumulative incidence analysis. Main outcome measures:Baseline tests obtained were: herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) Western blots, hepatitis B, and syphilis serologies; anorectal and pharyngeal Neisseria gonorrhoeae (GC) cultures; first-catch urine for leukocyte esterase (LE) and Chlamydia trachomatis (CT) ligase chain reaction (LCR). Men with a positive urine LE had urethral GC cultures obtained. The following outcomes were measured over 12 months follow-up: incident symptomatic bacterial STD (urethritis, proctitis, epididymitis), HSV-1 and HSV-2 seroconversion, and HIV-1 seroconversion. The 31 incident cases of STD (men with bacterial STD) were compared with those 489 men without symptomatic bacterial STD or seroconversion to HSV-1, HSV-2 or HIV-1 infection. Results:Bacterial STD were found in nine participants at enrollment; there were two cases of nonchlamydial urethritis, two cases of nonchlamydial epididymitis, and five cases of asymptomatic GC infection. At enrollment, HSV-2 antibodies were detected in 149 (26.0%) of 572 men and prior hepatitis B infection in 145 (34.8%) of 417 unvaccinated men. During the 1-year of follow-up, 31 men (5.7/100 person-years) had 34 episodes of a symptomatic bacterial STD syndrome (urethritis, epididymitis or proctitis). Urethritis was the most common STD syndrome, detected in 29 men, of whom 10 had GC and 19 had nongonococcal urethritis. In the 1-year of follow-up, five participants seroconverted to HIV-1 (1.3/100 person-years), four to HSV-2 (1.0/100 person-years), and seven to HSV-1 (4.3/100 person-years). Unprotected insertive anal sex [odds ratio (OR) 2.6; 95% confidence interval (CI) 1.2–5.6]; and nitrite inhalant (‘poppers’) use (OR, 2.3; 95% Cl, 1.0–5.0) were independently associated with incident STD. Conclusions:STD and HIV infection continue to be acquired even in a city with an overall low bacterial STD prevalence and among educated MSM receiving regular HIV screening and risk-reduction. Urethritis was the most common STD detected, and public health messages aimed at MSM need to emphasize safe insertive as well as receptive sexual practices.

Sexual behaviors and risk factors for HIV infection among men who have sex with men in the Dominican Republic.

Objective:To describe self-reported types of sexual identity of men who have sex with men (MSM) in the Dominican Republic, assess sociodemographics and behavioral characteristics, and measure the prevalence of HIV-1 and syphilis. Design:Cross-sectional study of MSM recruited from a variety of community settings. Methods:A total of 354 men agreed to participate after giving verbal informed consent. Information was obtained using a standardized questionnaire assessing demographics and AIDS-relevant information. Blood was obtained for HIV and syphilis testing. Results:Five main sexual identity groups emerged: cross dressers, homosexuals, gigolos, bisexuals and heterosexuals. Receptive anal and oral intercourse were commonly reported by men self-identifying as cross dressers or homosexuals, whereas nearly all of the remaining three groups practiced only insertive intercourse. Sexual contact with women was also commonly reported; overall, consistent condom use was infrequent. HIV antibodies were detected in 11.0% and serologic evidence of syphilis was found in 7.3%. Factors independently associated with HIV infection included serologic evidence of syphilis, having visited at least one of four local brothels in 1975–1985, and having had receptive anal intercourse with four or more partners in the last 12 months. Conclusions:Syphilis, sexual practices and social context of sex (commercial sex), rather than sexual identity per se, were associated with HIV infection. The complex social networks of MSM in this setting, the tendency to practice either insertive or receptive sex, but not both, infrequent condom use, high rates of syphilis and the frequency of sex with women need to be taken into account for targeted HIV prevention programs to be successful.

Safety and acceptability of penile application of 2 candidate topical microbicides: BufferGel and PRO 2000 Gel: 3 randomized trials in healthy low-risk men and HIV-positive men.

Objectives: To assess safety and acceptability of penile application of BufferGel (ReProtect, Baltimore, MD) and PRO 2000 Gel (Indevus Pharmaceuticals, Lexington, MA)compared with placebo among low‐risk sexually abstinent men and HIV‐positive sexually abstinent men. Design: Seventy‐two healthy low‐risk men (36 uncircumcised) and 25 HIV‐positive men (12 uncircumcised) were enrolled in 3 double‐blind, single‐center studies as follows: 36 low‐risk men in a study of BufferGel and K‐Y Jelly (McNeil‐PPC, Skillman, NJ) placebo; 36 low‐risk men in a study of PRO 2000 Gel and vehicle placebo; and 25 HIV‐positive men in a crossover study of BufferGel, PRO 2000 Gel, and K‐Y Jelly placebo. Methods: Participants applied product to the penis on 7 consecutive nights, kept study diaries, and were then interviewed and examined. Urine was tested for inflammation by leukocyte esterase. Results: No serious adverse events (AEs) or urethral inflammation was detected. During use of BufferGel, 3 low‐risk men (13%) reported 6 AEs and 2 HIV‐positive men (8%) reported 3 AEs. During use of PRO 2000 Gel, 4 low‐risk men (17%) reported 6 AEs and 1 HIV‐positive participant (4%) had 1 AE. AE rates during use of BufferGel and PRO 2000 Gel use were not significantly different from rates observed during placebo. One low‐risk man (4%) would object to his partners using BufferGel and 3 (13%) to PRO 2000 Gel. Two HIV‐positive men (8%) reported they would object to partners using either BufferGel or PRO 2000 Gel. Conclusions: Daily application of BufferGel and PRO 2000 Gel directly to the penis consecutively for 7 days was generally safe and well tolerated among healthy low‐risk men and HIV‐positive men. These microbicides have acceptable safety profiles to proceed with planned phase 3 vaginal microbicide trials.

Brief report: effectiveness of combination antiretroviral therapy on survival and opportunistic infections in a developing world setting: an observational cohort study.

Background:The prolonged effectiveness of antiretroviral therapy (ART) in a developing country is not well established. Methods:An observational database was established at the HIV clinic of the Almenara Hospital in Lima, Peru in 1996. All 564 initially antiretroviral-naive HIV-infected persons (mean CD4 count of 91 cells/mm3) who received combination ART were followed over time. Results:The overall survival rate was 96% at year 2, 94% at year 4, and 91% at year 5. Among persons who initiated therapy with CD4 counts <100 cells/mm3, the overall survival rate at 3 years was 95%. Opportunistic infections while on ART occurred in 20% of persons. Patients who received 2 reverse transcriptase (RT) inhibitors plus a protease inhibitor had slightly better survival rates and less opportunistic disease in the first year of therapy as compared with those receiving 2 RT inhibitors and a nonnucleoside reverse transcriptase inhibitor or 3 RT inhibitors. Conclusions:This study demonstrates the long-term effectiveness of ART in a developing country urban setting. It provides evidence of the importance of continuing global financing initiatives to provide widespread HIV therapy for countries in the developing world.

Acceptability of a bioadhesive Nonoxynol-9 gel delivered by an applicator as a rectal microbicide

BACKGROUND AND OBJECTIVES Potential rectal microbicides, as an adjunct to condoms for HIV/STD prevention, have not been studied previously. GOAL OF THIS STUDY Advantage 24 (1.5 ml of a bioadhesive gel containing 52.5 mg nonoxynol-9 administered by single-use applicator)-under investigation as a vaginal microbicide-was evaluated for acceptability among male couples. STUDY DESIGN Twenty-five HIV-negative and 10 HIV-positive male couples participated in a frequency use escalation trial. Diaries and self-administered questionnaires assessed product use, acceptability, sexual behavior, and gastrointestinal and urologic side effects. RESULTS Excluding participants who felt no need for an HIV prevention method, 58% said they would use Advantage 24 if approved for rectal use; 69% of receptive users reported rectal fullness and related side effects after insertion of the gel, and 68% reported applicator-related discomfort; 59% of insertive participants found the gel too sticky. CONCLUSIONS Acceptability remains inconclusive and warrants further study of redesigned applicators and ways to minimize rectal side effects.

Safety and acceptability of the Reality condom for anal sex among men who have sex with men.

Objectives: To assess safety and acceptability of RealityTM condoms for anal sex among men who have sex with men. Methods: Crossover study among HIV-seroconcordant (33 HIV-negative and 5 HIV-positive) monogamous male couples, randomized to latex male and Reality condom use with anal sex. Results: Slippage with removal was reported more frequently with Reality than male latex condoms [odds ratio (OR), 2.7; 95% confidence interval (CI), 1.2–5.8 for receptive partners and OR, 34.1; 95% CI, 13.8–84.1 for insertive partners]. Receptive partners more frequently reported pain or discomfort (OR, 5.0; 95% CI, 2.6–9.4) and rectal bleeding (OR, 1.9; 95% CI, 0.9–4.1) with Reality condoms than male condoms. Over 20% reported willingness to use the Reality condom in the future with a partner of unknown HIV status; willingness was associated with past problems with male condoms and no problems with Reality condoms among receptive partners, and with past use of Reality condoms and HIV seropositivity among insertive partners. Conclusions: Men reported more frequent problems with Reality condoms than male latex condoms used for anal intercourse, particularly slippage, discomfort, and rectal bleeding. Design modifications, training, and research on the clinical significance of safety outcomes are needed for use of Reality condoms with anal sex.

Bacterial infections in adult patients hospitalized with AIDS: case-control study of prophylactic efficacy of trimethoprim-sulfamethoxazole versus aerosolized pentamidine

To determine the association between trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis for Pneumocystis carinii pneumonia and risk of bacterial infections in persons with AIDS, we abstracted hospital records from 6496 adult admissions to 42 hospitals in western Washington state. Of these admissions, 570 involved 637 bacterial infections diagnosed among patients who had been prescribed prophylactic TMP-SMX or aerosolized pentamidine. Cases [admissions with bacteraemia, bacterial pneumonia, acute or chronic sinusitis, or urinary tract infection (UTI)] were compared to controls (admissions not associated with any of the 5 bacterial infections). After adjusting for CD4 lymphocyte count and presence of P. carinii pneumonia, TMP-SMX prophylaxis, relative to aerosolized pentamidine prophylaxis, was associated with a reduced risk of bacteraemia (adjusted OR=0.5; 95% CI, 0.2-1.0; P =0.04), bacterial pneumonia (adjusted OR=0.5; 95% CI, 0.3-0.8; P =0.01), acute sinusitis (adjusted OR=0.5; 95% CI, 0.2-1.3; P =0.2), chronic sinusitis (adjusted OR=0.3; 95% CI, 0.1-0.7; P =0.01), and UTI (adjusted OR=0.5; 95% CI, 0.2-1.2; P =0.1), and all 5 bacterial infections combined (adjusted OR=0.6; 95% CI, 0.5-0.8; P 0.001). <