Systematic Review: Strategies for Improving HIV Testing and Detection Rates in European Hospitals.

Undiagnosed HIV infection is a prominent clinical issue throughout Europe that requires the continuous attention of all healthcare professionals and policymakers to prevent missed testing opportunities and late diagnosis. This systematic review aimed to evaluate interventions to increase HIV testing rates and case detection in European hospitals. Out of 4598 articles identified, 29 studies fulfilled the selection criteria. Most of the studies were conducted in single Western European capital cities, and only one study was from Eastern Europe. The main interventions investigated were test-all and indicator-condition-based testing strategies. Overall, the prevalence of undiagnosed HIV was well above 0.1%. The studied interventions increased the HIV testing rate and the case detection rate. The highest prevalence of undiagnosed HIV was found with the indicator-condition-driven testing strategy, whereas the test-all strategy had the most profound impact on the proportion of late diagnoses. Nevertheless, the HIV testing rates and case-finding varied considerably across studies. In conclusion, effective strategies to promote HIV testing in European hospitals are available, but relevant knowledge gaps regarding generalizability and sustainability remain. These gaps require the promotion of adherence to HIV testing guidelines, as well as additional larger studies representing all European regions.

The efficacy and tolerability of latency-reversing agents in reactivating the HIV-1 reservoir in clinical studies: a systematic review.

Introduction: Understanding the clinical potency of latency-reversing agents (LRAs) on the HIV-1 reservoir is useful to deploy future strategies. This systematic review evaluated the effects of LRAs in human intervention studies. Methods: A literature search was performed using medical databases focusing on studies with adults living with HIV-1 receiving LRAs. Eligibility criteria required participants from prospective clinical studies, a studied compound hypothesised as LRA, and reactivation or tolerability assessments. Relevant demographical data, LRA reactivation capacity, reservoir size, and adverse events were extracted. A study quality assessment with analysis of bias was performed by RoB 2 and ROBINS-I tools. The primary endpoints were HIV-1 reservoir reactivation after LRA treatment quantified by cell-associated unspliced HIV-1 RNA, and LRA tolerability defined by adverse events. Secondary outcomes were reservoir size and the effect of LRAs on analytical treatment interruption (ATI) duration. Results: After excluding duplicates, 5182 publications were screened. In total 45 publications fulfilled eligibility criteria including 26 intervention studies and 16 randomised trials. The risk of bias was evaluated as high. Chromatin modulators were the main investigated LRA class in 24 studies. Participants were mostly males (90.1%). Where reported, HIV-1 subtype B was most frequently observed. Reactivation after LRA treatment occurred in 78% of studies and was observed with nearly all chromatin modulators. When measured, reactivation mostly occurred within 24 h after treatment initiation. Combination LRA strategies have been infrequently studied and were without synergistic reactivation. Adverse events, where reported, were mostly low grade, yet occurred frequently. Seven studies had individuals who discontinued LRAs for related adverse events. The reservoir size was assessed by HIV-1 DNA in 80% of studies. A small decrease in reservoir was observed in three studies on immune checkpoint inhibitors and the histone deacetylase inhibitors romidepsin and chidamide. No clear effect of LRAs on ATI duration was observed. Conclusion: This systematic review provides a summary of the reactivation of LRAs used in current clinical trials whilst highlighting the importance of pharmacovigilance. Highly heterogeneous study designs and underrepresentation of relevant patient groups are to be considered when interpreting these results. The observed reactivation did not lead to cure or a significant reduction in the size of the reservoir. Finding more effective LRAs by including well-designed studies are needed to define the required reactivation level to reduce the HIV-1 reservoir.

Anti-spike protein to determine SARS-CoV-2 antibody levels: Is there a specific threshold conferring protection in immunocompromised patients?

BACKGROUND: Identifying a specific threshold level of SARS-CoV-2 antibodies that confers protection in immunocompromised patients has been very challenging. The aim was to assess the threshold of 264 binding antibody units (BAU)/ml using four different SARS-CoV-2 antibody assays (Abbott, Beckman, Roche, and Siemens) and to establish a new optimal threshold of protection for each of the four antibody assays. METHODS: This study was performed on data retrieved from 69 individuals, who received at least one dose of the Pfizer/BioNTech BNT162b2 or Moderna COVID-19 vaccine (Spikevax) at the Alphabio Laboratory in Marseille, France (European Hospital, Alphabio-Biogroup). The results were compared to the percent inhibition calculated using a functional surrogate of a standardized virus neutralization test (Genscript). RESULTS: Samples from 69 patients were analyzed. For a reference cutoff of 264 BAU/ml, assays showed moderate to good overall concordance with Genscript: 87% concordance for Abbott, 78% for Beckman, 75% for Roche, and 88% for Siemens. Overall concordance increased consistently after applying new thresholds, i.e., 148 BAU/ml (Abbott), 48 (Beckman), 559 (Roche), and 270 (Siemens). CONCLUSION: We suggest specific adjusted thresholds (BAU/ml) for the four commercial antibody assays that are used to assess pre-exposure prophylaxis in immunocompromised patients.

A cohort analysis of sexually transmitted infections among different groups of men who have sex with men in the early era of HIV pre-exposure prophylaxis in France.

BACKGROUND: MSM are at particular risk of STIs due to sexual behavior and substance use. HIV PrEP use may increase this risk. DESIGN: Our aim was to comparatively assess incident STIs among different at-risk groups-PLWHIV, HIV-negative PrEP and no-PrEP users-seen at our center early after PrEP implementation. METHODS: Clinical data were retrospectively collected on 636 MSM seen at the Infectious Diseases Department between September 2016 and October 2018. STI incidence rate was assessed among groups for the whole period, as well as separately for each year of the study. RESULTS: Overall STI incidence rate ratio was higher in HIV-neg when compared to PLWHIV. In multivariate analysis, STI risk was significantly higher among HIV-neg no-PrEP users compared to PLWHIV, while not different between PLWHIV and PrEP users.STI incidence globally increased during the first 2 years after PrEP approval among PLWHIV and no-PrEP users, stated by odds ratio (OR = 1.77 [1.23-2.55], p = 0.0020 and OR = 2.29 [0.91-5.73], p = 0.0774 respectively) while it remained rather stable for HIV-neg PrEP users (OR = 1.19 [0.60-2.38], p = 0.6181). The HIV-neg no-PrEP group remained at higher risk of STI than PLWHIV and PrEP users during the two periods. CONCLUSION: These results suggest that a proactive approach of an efficient follow-up of MSM participants since PrEP approval may have prevented an increase of the incidence of STIs among PrEP users.

Polypharmacy Is Associated With Falls in Women With and Without HIV.

BACKGROUND: Aging in people with HIV is associated with increased risk of developing synergistic conditions such as neurocognitive impairment, polypharmacy, and falls. We assessed associations between polypharmacy (use of 5 or more non-ART medications), use of neurocognitive adverse effects (NCAE) medications, and odds of falls in women with HIV (WWH) and without HIV (HIV-). METHODS: Self-reported falls and medication use data were contributed semiannually by 1872 (1315 WWH and 557 HIV-) Women's Interagency HIV Study participants between 2014 and 2016. Polypharmacy and NCAE medication use were evaluated separately and jointly in multivariable models to assess their independent contributions to single and multiple falls risk. RESULTS: The proportion of women who reported any fall was similar by HIV status (19%). WWH reported both greater polypharmacy (51% vs. 41%; P < 0.001) and NCAE medication use (44% vs. 37%; P = 0.01) than HIV- women. Polypharmacy conferred elevated odds of single fall [adjusted odds ratio (aOR) 1.67, 95% CI: 1.36 to 2.06; P < 0.001] and multiple falls (aOR 2.31, 95% CI: 1.83 to 2.93; P < 0.001); the results for NCAE medications and falls were similar. Both polypharmacy and number of NCAE medications remained strongly and independently associated with falls in multivariable models adjusted for HIV serostatus, study site, sociodemographics, clinical characteristics, and substance use. CONCLUSIONS: Polypharmacy and NCAE medication use were greater among WWH compared with HIV-, and both were independently and incrementally related to falls. Deprescribing and avoidance of medications with NCAEs may be an important consideration for reducing fall risk among WWH and sociodemographically similar women without HIV.

Predicting Post-treatment HIV Remission: Does Size of the Viral Reservoir Matter?

Combination antiretroviral therapy (ART) suppresses human immunodeficiency virus (HIV) replication and improves immune function. However, due to the persistence of long-lived HIV reservoirs, therapy interruption almost inevitably leads to a fast viral rebound. A small percentage of individuals who are able to control HIV replication for extended periods after therapy interruption are of particular interest because they may represent a model of long-term HIV remission without ART. These individuals are characterized by a limited viral reservoir and low reservoir measures can predict post-treatment HIV remission. However, most individuals with a low reservoir still experience fast viral rebound. In this Perspective, we discuss the possible reasons behind this and propose to develop an integral profile, composed of viral and host biomarkers, that could allow the accurate prediction of post-treatment HIV remission. We also propose to incorporate information on the chromatin context of the proviral integration sites into the characterization of the HIV reservoir, as this likely influences the reactivation capacity of latent proviruses and, together with the actual number of intact proviruses, contributes to the replication competence of the reservoir.

Highlights from the 22nd International AIDS Conference (AIDS 2018), 22-27 July 2018, Amsterdam, the Netherlands.

Important data on the social, epidemiological and clinical aspects of HIV-1, comorbidities and hepatitis as well as data on novel antiretroviral agents and the cure agenda were presented at AIDS 2018. This report covers some of the highlights.

Highlights from the 8th International Workshop on HIV Persistence during Therapy, 12-15 December 2017, Miami, FL, USA.

Over 4 days, more than 500 scientists involved in HIV persistence research shared their new unpublished data and designed future perspectives towards ART-free HIV remission. This 8th International Workshop on HIV Persistence followed the format of past conferences but further focused on encouraging participation of young investigators, especially through submission of oral and poster presentations. The topic of the workshop was HIV persistence. Consequently, issues of HIV reservoirs and HIV cure were also addressed. In this article, we report the discussions as closely as possible; however, all the workshop abstracts can be found online at www.viruseradication.com.