On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection.

BACKGROUND: Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen. METHODS: We conducted a double-blind, randomized trial of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counseling and condoms and were regularly tested for HIV-1 and HIV-2 and other sexually transmitted infections. RESULTS: Of the 414 participants who underwent randomization, 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group). All participants were followed for a median of 9.3 months (interquartile range, 4.9 to 20.6). A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002). Participants took a median of 15 pills of TDF-FTC or placebo per month (P=0.57). The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03). CONCLUSIONS: The use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. The treatment was associated with increased rates of gastrointestinal and renal adverse events. (Funded by the National Agency of Research on AIDS and Viral Hepatitis [ANRS] and others; ClinicalTrials.gov number, NCT01473472.).

Multidrug-resistant Neisseria gonorrhoeae failing treatment with ceftriaxone and doxycycline in France, November 2017.

We report a multidrug-resistant Neisseria gonorrhoeae urogenital and pharyngeal infection with ceftriaxone resistance and intermediate resistance to azithromycin in a heterosexual woman in her 20s in France. Treatment with ceftriaxone plus doxycycline failed for the pharyngeal localisation. Whole-genome sequencing of isolate F90 identified MLST1903, NG-MAST ST3435, NG-STAR233, and relevant resistance determinants. F90 showed phenotypic and genotypic similarities to an internationally spreading multidrug-resistant and ceftriaxone-resistant clone detected in Japan and subsequently in Australia, Canada and Denmark.

Peripheral T-cell lymphoma in HIV-infected patients: a study of 17 cases in the combination antiretroviral therapy era.

Most cases of human immunodeficiency virus (HIV)-associated non-Hodgkin Lymphoma (NHL) are of B-cell origin; T-cell NHLs are rarely reported. Within a single centre prospective cohort of 370 HIV-NHL, 17 (5%) were of T-cell origin (82% male; median age, 39 years). Median CD4+ cell count was 0·194 × 10(9) /l and 41% had undetectable plasma HIV-RNA at lymphoma diagnosis. All patients received combination antiretroviral therapy during chemotherapy. All histological samples were centrally reviewed. The distribution of the histological subtypes differed from the general population with absence of angioimmunoblastic subtype. Lymphoma was disseminated in 14 patients, and seven patients had performance status >2. All patients received full-dose chemotherapy: eight standard and nine intensive regimens. Two patients who received intensive chemotherapy died during therapy. The complete remission rate was 53%; 62·5% with standard therapy and 44% with intensive therapy. After a median follow-up of 7·2 years, the median overall survival was 9·4 months. Most deaths (85%) occurred within the first year following diagnosis, as a consequence of lymphoma progression in 10/13 cases. In this rare but severe complication of HIV infection the use of intensive chemotherapy does not appear to be beneficial for response, with increased toxicity.

Trends in asymptomatic STI among HIV-positive MSM and lessons for systematic screening.

The burden of STIs is particularly high in HIV-infected MSM patients. A recent increase in STIs prevalence has been noticed in the US and western European countries. We aim to assess trends in asymptomatic STIs following the publication of recommendations for STIs screening, i.e. Chlamydia (CT) and gonorrhea (NG). Seventeen centers located in the Paris area participated in the study. All asymptomatic HIV-infected MSM patients attending a follow up consultation were proposed to participated in the study. Asymptomatic patients were included over 2 periods: period 1 from April to December 2015 and period 2 from September to December 2017. Etiologic diagnosis of STIs including hepatitis B, C, syphilis, was performed using a serological test, including a non-treponemal titer with a confirmatory treponemal assay for syphilis. CT and NG were screened using a nucleic acid amplification test (NAATs) on 3 anatomical sites, i.e. urine, rectal and pharyngeal. Overall, 781 patients were included: 490 and 291 in periods 1 and 2 respectively. Asymptomatic CT, NG, and syphilis were diagnosed in 7.5%, 4.8% and, 4.2% respectively. The rate of patients having a multisite asymptomatic infection was 10.2% and 21.1% for CT and NG respectively. The most frequently involved anatomical sites for CT and NG asymptomatic infections were anorectal (66.1% and 55.2% respectively) and pharyngeal (47.4% and 60.5% respectively). CT and NG asymptomatic infection increased by 1.3- and 2-fold respectively between the two periods while syphilis decreased by 3 folds. Our results encourage to reconsider multisite screening for CT and NG in asymptomatic HIV positive MSM as the yield of screening urinary samples only might be low. Despite the more systematic STI screening of asymptomatic HIV positive MSM the prevalence of STI is increasing in MSM in France. Therefore, this strategy has not led to alter CT and NG transmission. The decrease of syphilis might involve self-medication by doxycycline, and the intensification of syphilis screening.

Impact of low-level-viremia on HIV-1 drug-resistance evolution among antiretroviral treated-patients.

BACKGROUND: Drug-resistance mutations (DRAM) are frequently selected in patients with virological failure defined as viral load (pVL) above 500 copies/ml (c/mL), but few resistance data are available at low-level viremia (LLV). Our objective was to determine the emergence and evolution of DRAM during LLV in HIV-1-infected patients while receiving antiretroviral therapy (ART). METHODS: Retrospective analysis of patients presenting a LLV episode defined as pVL between 40 and 500 c/mL on at least 3 occasions during a 6-month period or longer while on the same ART. Resistance genotypic testing was performed at the onset and at the end of LLV period. Emerging DRAM was defined during LLV if never detected on baseline genotype or before. RESULTS: 48 patients including 4 naive and 44 pretreated (median 9 years) presented a LLV episode with a median duration of 11 months. Current ART included 2NRTI (94%), ritonavir-boosted PI (94%), NNRTI (23%), and/or raltegravir (19%). Median pVL during LLV was 134 c/mL. Successful resistance testing at both onset and end of the LLV episode were obtained for 37 patients (77%), among who 11 (30%) acquired at least 1 DRAM during the LLV period: for NRTI in 6, for NNRTI in 1, for PI in 4, and for raltegravir in 2. During the LLV period, number of drugs with genotypic resistance increased from a median of 4.5 to 6 drugs. Duration and pVL level of LLV episode, duration of previous ART, current and nadir CD4 count, number of baseline DRAM and GSS were not identified as predictive factors of resistance acquisition during LLV, probably due to limited number of patients. CONCLUSION: Persistent LLV episodes below 500 c/ml while receiving ART is associated with emerging DRAM for all drug classes and a decreasing in further therapeutic options, suggesting to earlier consider resistance monitoring and ART optimization in this setting.

Comparative RNA quantification of HIV-1 group M and non-M with the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 v2.0 and Abbott Real-Time HIV-1 PCR assays.

BACKGROUND: A new version of the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 assay (CA/CTM v2.0) has been introduced to overcome the underquantification observed with the first version. METHODS: We compared the Roche Cobas CA/CTM v2.0 and Abbott RealTime HIV-1 assays for HIV-1 group M and non-M viral load measurement. RESULTS: We found a good correlation (r = 0.96) between the 2 techniques for the 260 HIV-1 group M plasma samples tested. The Roche Cobas assay gave significantly higher values than the Abbott assay, and 51 samples (20%) yielded differences greater than 0.5 log10 copies per milliliter. Conversely, 2 samples were more than 0.5 log10 copies per milliliter higher with the Abbott assay than with the Roche Cobas assay. Among the 84 samples with undetectable viral load in the Abbott assay (detection limit 40 copies/mL), 17 (20%) were detectable with the CA/CTM v2.0 assay (detection limit 20 copies/mL), with values ranging from 41 to 897 copies per milliliter. Extrapolation of the Abbott curves led to 10/17 (59%) of these samples being quantifiable. HIV-1 groups O and P were similarly quantified by the two techniques. CONCLUSION: The results of the Roche Cobas CA/CTM v2.0 and Abbott RealTime HIV-1 assays correlate well. The new version of the CA/CTM assay shows improved sensitivity. Nevertheless, the 2 assays differ by more than 0.5 log10 copies per milliliter for some samples.