The Safety of Tenofovir-Emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP) in Individuals With Active Hepatitis B.

BACKGROUND: Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated. METHODS: The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection. RESULTS: Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series. CONCLUSIONS: PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered.

Evolution of the syphilis epidemic among men who have sex with men.

Syphilis has existed for millenni, but its epidemiology was only recently linked to men who have sex with men (MSM) after the introduction of penicillin in the 1940s; the syphilis epidemic became concentrated within the MSM community in subsequent decades. The HIV/AIDS epidemic in the 1980s led to a surge of new syphilis cases and revealed the potentiation between HIV and syphilis, as evidenced by a shift in the natural history of neurosyphilis. In response, MSM revolutionised their sexual behaviour by implementing community-driven seroadaptive strategies to stem HIV transmission. The Centers for Disease Control in the US called for the elimination of syphilis in the late 1990s since the rates had fallen sharply but this effort was overtaken by a resurgence of global outbreaks among MSM in the 2000s, many of which were linked to methamphetamine use and sexual networking websites. Syphilis remains highly prevalent today, especially among MSM and individuals infected with HIV, and it continues to present a significant public health conundrum. Innovative syphilis prevention strategies are warranted. MSM engaging in high-risk behaviour such as condomless anal receptive intercourse, sex with multiple partners or recreational drug use should be routinely screened for syphilis infection; they should also be counselled about the limits of seroadaptive behaviours and HIV pre-exposure prophylaxis as they relate to syphilis transmission.

Transactional sex and prevalence of STIs: a cross-sectional study of MSM and transwomen screened for an HIV prevention trial.

Few studies have characterised the degree of engagement in transactional sex among men and transgender women who have sex with men and explored its association with sexually transmitted infections and human immunodeficiency virus in Ecuador. We screened 642 men who have sex with men and transgender women for a pre-exposure prophylaxis clinical trial (iPrEx) in Guayaquil, Ecuador, 2007-2009. We analysed the association of degree of engagement in transactional sex and prevalence of sexually transmitted infections including human immunodeficiency virus using chi-square and analysis of variance tests. Although just 6.2% of those who screened self-identified as sex workers, 52.1% reported having engaged in transactional sex. Compared to those who had never been paid for sex, those who had been paid were more likely to have a sexually transmitted infection (56.6% vs. 45.0%, p = 0.007) and trended towards a higher human immunodeficiency virus prevalence (16.6% vs. 10.4%, p = 0.082) at screening. Transgender women compared to other men who have sex with men were more likely to have sexually transmitted infections diagnosed at screening (75.6% vs. 50.0%, p = 0.001). Transactional sex is practiced widely but occasionally among the men who have sex with men and transgender women in Guayaquil who screened for the iPrEx study; however, engaging in transactional sex may not lead to a sex worker self-identification. Both transactional sex and being a transgender woman are associated with sexually transmitted infections prevalence.

Syphilis predicts HIV incidence among men and transgender women who have sex with men in a preexposure prophylaxis trial.

BACKGROUND: Syphilis infection may potentiate transmission of human immunodeficiency virus (HIV). We sought to determine the extent to which HIV acquisition was associated with syphilis infection within an HIV preexposure prophylaxis (PrEP) trial and whether emtricitabine/tenofovir (FTC/TDF) modified that association. METHODS: The Preexposure Prophylaxis Initiative (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily FTC/TDF or placebo. Syphilis prevalence at screening and incidence during follow-up were measured. Hazard ratios for the effect of incident syphilis on HIV acquisition were calculated. The effect of FTC/TDF on incident syphilis and HIV acquisition was assessed. RESULTS: Of 2499 individuals, 360 (14.4%) had a positive rapid plasma reagin test at screening; 333 (92.5%) had a positive confirmatory test, which did not differ between the arms (FTC/TDF vs placebo, P = .81). The overall syphilis incidence during the trial was 7.3 cases per 100 person-years. There was no difference in syphilis incidence between the study arms (7.8 cases per 100 person-years for FTC/TDF vs 6.8 cases per 100 person-years for placebo, P = .304). HIV incidence varied by incident syphilis (2.8 cases per 100 person-years for no syphilis vs 8.0 cases per 100 person-years for incident syphilis), reflecting a hazard ratio of 2.6 (95% confidence interval, 1.6-4.4; P < .001). There was no evidence for interaction between randomization to the FTC/TDF arm and incident syphilis on HIV incidence. CONCLUSIONS: In HIV-seronegative MSM, syphilis infection was associated with HIV acquisition in this PrEP trial; a syphilis diagnosis should prompt providers to offer PrEP unless otherwise contraindicated.

Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis.

OBJECTIVE: Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons. DESIGN AND METHODS: The Iniciativa Profilaxis Pre-Exposición (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily TDF coformulated with emtricitabine (FTC/TDF) or placebo. Serum creatinine and phosphorus during randomized treatment and after discontinuation were measured, and creatinine clearance (CrCl) was estimated by the Cockcroft-Gault equation. Indicators of proximal renal tubulopathy (fractional excretion of phosphorus and uric acid, urine protein, and glucose) were measured in a substudy. RESULTS: There was a small but statistically significant decrease in CrCl from baseline in the active arm, compared to placebo, which was first observed at week 4 (mean change: -2.4 vs. -1.1 ml/min; P=0.02), persisted through the last on-treatment visit (mean change: +0.3 vs. +1.8 ml/min; P=0.02), and resolved after stopping pre-exposure prophylaxis (mean change: -0.1 vs. 0.0 ml/min; P=0.83). The effect was confirmed when stratifying by drug detection. The effect of FTC/TDF on CrCl did not vary by race, age, or history of hypertension. There was no difference in serum phosphate trends between the treatment arms. In the substudy, two participants receiving placebo had indicators of tubulopathy. CONCLUSIONS: In HIV-seronegative MSM, randomization to FTC/TDF was associated with a very mild nonprogressive decrease in CrCl that was reversible and managed with routine serum creatinine monitoring.