Dynamics of HIV PrEP use and coverage during and after COVID-19 in Germany.

BACKGROUND: Pre-exposure prophylaxis (PrEP) with oral emtricitabine/tenofovir disoproxil (FTC/TDF) proved highly efficient in preventing HIV. Since 09/2019, FTC/TDF-PrEP is covered by health insurances in Germany, if prescribed by licensed specialists. However, methods to longitudinally monitor progress in PrEP implementation in Germany are lacking. METHODS: Utilizing anonymous FTC/TDF prescription data from 2017-2021, we developed a mathematical model to disentangle HIV-treatment from PrEP prescriptions, as well as to translate PrEP prescriptions into number of PrEP users. We used the model to estimate past- and future PrEP uptake dynamics, to predict coverage of PrEP needs and to quantify the impact of COVID-19 on PrEP uptake on a national and regional level. RESULTS: We identified significant (p<0.01) decelerating effects of the first- and second COVID-19-lockdown on PrEP uptake in 04/2020 and 12/2020. We estimated 26,159 (CI: 25,751-26,571) PrEP users by 12/2021, corresponding to 33% PrEP coverage of people in need. We projected 64,794 (CI: 62,956-66,557) PrEP users by 12/2030, corresponding to 81% PrEP coverage. We identified profound regional differences, with high PrEP coverage and uptake in metropoles and low coverage in more rural regions. CONCLUSIONS: Our approach presents a comprehensive solution to monitor and forecast PrEP implementation from anonymous data and highlighted that the COVID-19 pandemic significantly decelerated PrEP uptake in Germany. Moreover, slow PrEP uptake in rural areas indicate that structural barriers in PrEP care, education or information exist that may hamper the goal of ending the AIDS epidemic by 2030.

HPTN 083-02: factors influencing adherence to injectable PrEP and retention in an injectable PrEP study.

INTRODUCTION: HPTN 083 demonstrated the superiority of long-acting cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre-exposure prophylaxis (PrEP) among cisgender men and transgender women who have sex with men (MSM/TGW). HPTN 083 provided the first opportunity to understand experiences with injectable PrEP in a clinical trial. METHODS: Participants from two US sites (Chicago, IL and Atlanta, GA) and one international site (Rio de Janeiro, Brazil) were purposively sampled for individual qualitative interviews (N = 40), between November 2019 and March 2020, to explore trial experiences, barriers to adherence and other factors that may have impacted study implementation or outcomes. The blinded phase ended early due to efficacy; this analysis includes interviews conducted prior to unblinding with three groups defined by adherence (i.e. injection visit attendance): adherent (n = 27), non-adherent (n = 12) and early discontinuers (n = 1). Data were organized using NVivo software and analysed using content analysis. RESULTS: Participants (mean age: 27) were primarily cisgender MSM (90%) and Black/African American (60%). Reasons for trial enrolment and PrEP use included a preference for using HIV prevention medication versus treatment in the event of HIV acquisition; the ability to enhance health via study-related education and services; access to a novel, convenient HIV prevention product at no cost; and contributing to MSM/TGW communities through research. Participants contrasted positive experiences with study staff with their routine clinical care, and emphasized increased scheduling flexibility, thorough communication, non-judgemental counselling and open, affirming environments (e.g. compassion, less stigma) as adherence facilitators. Injection experiences were positive overall; some described early injection-related anxiety, which abated with time and when given some measure of control (e.g. pre-injection countdown), and minimal injection site discomfort. Some concerns and misperceptions about injectable PrEP were reported. Barriers to adherence, across all adherence categories, included structural factors (e.g. financial constraints, travel) and competing demands (e.g. work schedules). CONCLUSIONS: Respondents viewed injectable PrEP trial participation as a positive experience and a means of enhancing wellbeing. Study site flexibility and affirming clinic environments, inclusive of non-judgemental counselling, were key facilitators of adherence. To support injection persistence, interventions that address structural barriers and promote flexible means of injection delivery may be most effective.

Preexposition Prophylaxis With Truvada (Tenofovir/Emtricitabine) as Potential Cause of Celiac Disease-Like Enteropathy.

We present here a case of a 39-year-old patient who presented with celiac-disease-like symptoms and MARSH 3a histology in duodenal biopsies under normal diet. Interestingly, HLA genotyping and celiac-specific serology were negative, primarily leading to exclusion of celiac disease. However, biopsies from a second endoscopy a couple of months later (still under normal diet) showed histologic progression of the disease to MARSH 3b and led to the re-evaluation of the out-of-hospital-obtained histological samples by a pathologist experienced in celiac disease. The second biopsy described previously as MARSH 3b turned out to be non-specific and was therefore re-classified as MARSH 0. After all known causes of duodenal villous atrophy were excluded by a thorough evaluation, a correlation between the first biopsy (MARSH 3a) and Truvada intake could be established. After Truvada discontinuation and under normal diet, normalisation of duodenal mucosa was observed, leading to the assumption that Truvada could lead to celiac-like enteropathy.

Acceptability of the Dapivirine Vaginal Ring and Oral Truvada Among African Users in Late-Stage of Pregnancy.

The Microbicide Trials Network 042 study (MTN-042/DELIVER) is a two-arm, randomized, open-label Phase 3b trial that is evaluating the safety, adherence, and acceptability of the monthly ring and daily oral PrEP among HIV-uninfected pregnant people in four African countries. This analysis focuses on acceptability data captured qualitatively from a subset (n = 48) of the 150 people in the first cohort of the trial who were enrolled in late-stage pregnancy at 36 to 38 weeks gestational age and followed until after delivery. Single IDIs were conducted by trained interviewers at each clinic site using a semi-structured guide. Data excerpts of key codes pertaining to acceptability, pregnancy, and maternal health were summarized, reviewed and interpreted by multinational analyst teams. Although the product use period was relatively short, the data suggested several acceptability findings that may directly translate to longer durations of product use in pregnancy. The first was the overarching maternal sentiment that being able to protect both oneself and their baby was highly valued. The second was the importance of counseling support from providers not only because participants used methods that might generate side effects, but because pregnancy itself is a period with its own set of side effects. The third was that, similar to non-pregnant participants in other trials, here study products were generally liked and described as easy to use. Concerns about ring and oral PrEP use could be addressed with provider counseling and support and should form an essential component rollout among pregnant people.

Analysis of online user discussions on Reddit associated with the transition of use between HIV PrEP therapy.

In 2019, the U.S. Food and Drug Administration (FDA) approved emtricitabine and tenofovir alafenamide (Descovy) as another option for HIV pre-exposure prophylaxis (PrEP) prevention for high-risk adults and adolescents. With the introduction of this new PrEP, millions of current users on emtricitabine and tenofovir disoproxil fumarate (Truvada), another PrEP medication currently used to prevent HIV transmission, have options of whether to continue their current treatment regime or transition to new treatment options. The objective of this study was to conduct a descriptive analysis to characterize user-generated social media conversations on Reddit associated with FDA-approved PrEP prevention treatment options. Key themes identified were associated with perceptions, knowledge, and attitudes associated with the transition of use of different PrEP medications. Data were collected retrospectively and prospectively from the Reddit platform for posts with keywords filtered for HIV, PrEP, and FDA-approved PrEP prevention treatment from October 2020 to December 2020. We chose the Reddit platform based on prior studies that have identified PrEP user conversations and insights on access challenges for specific AIDS communities, such as gays and men who have sex with men (MSM). Reddit posts were then manually annotated using an inductive content coding approach for key themes regarding the transition of use and other emergent themes from user-generated content. Formal coding of text data was conducted with refined codes, and sub-codes created. A total of 3,120 posts were analyzed from Reddit resulting in 315 posts that were coded for PrEP and 105 posts (33.33%) specific to user discussions regarding the transition of PrEP prevention. Overall, users expressed interest in drug switching to Descovy, particularly in the context of poorer adherence or concerns about existing side effects associated with Truvada. Other major themes included discussions about the cost of Descovy, apprehension about side effects in comparison to Truvada, insurance coverage changes, and discussions about the donation of Truvada to other users after transitioning. Among these discussions, topics related to sexual minorities, including MSM, reported concerns when considering a switch in their HIV prevention regime. Understanding the changing public perception associated with the introduction of new HIV prevention is important in the context of market access, patient safety, pharmacovigilance, and health equity, particularly among high-risk populations such as MSM. Results support the use of social media from a digital pharmacovigilance perspective to better understand emerging HIV prevention, treatment, and adherence challenges experienced by patients.

Federal Funding For Discovery And Development Of Costly HIV Drugs Was Far More Than Previously Estimated.

In July 2012, tenofovir disoproxil fumarate-emtricitabine (TDF-FTC, brand name Truvada) was approved by the Food and Drug Administration (FDA) to prevent HIV infection. To estimate the extent of the US government's direct financial contribution to the discovery and development of Truvada, we identified National Institutes of Health awards using FDA documents, peer-reviewed literature, patent records, court filings, and other publicly available materials. We classified seventy-three federal government awards to eleven researchers as being directly linked to the development and clinical testing of Truvada for prevention therapy, through which the US government spent an estimated $143 million. The substantial public funding raises questions about the high price charged by the drug's manufacturer, which reduced its affordability and limited its accessibility as HIV preventive therapy.

HIV Prevention Research Experiences Among Men Who Have Sex With Men and Transgender Persons of Color.

PURPOSE: Black and Latinx MSM and transgender POC disproportionately experience new HIV diagnoses. Determining effective HIV prevention methods requires the inclusion of these communities in research and thorough post-trial experience evaluations. This study sought to evaluate the experiences of Black and Latinx MSM and transgender POC in HIV prevention research and identify facilitators and barriers to continued trials participation. METHODS: A survey was developed in partnership with the community engagement team based on emerging themes during research participant check-ins with the team. The survey was built in REDCap and distributed to participants via text message. The survey assessed experiences with the research process time commitments, study responsibilities, compensation, experiences with Truvada®, characteristics of the research study team and site, barriers to continued study participation, willingness to participate in future studies, and overall satisfaction. All statistical analysis was completed in Stata. RESULTS: Forty-four participants were enrolled in the study. Most participants (98%) were satisfied with their experiences in HIV prevention research. Job or school schedules were the most frequently cited barrier to study participation while Truvada® provision and adequate study visit compensation, length, number, and frequency were facilitators. Participants reported that research staff made them feel comfortable when talking about sexual behaviors, alcohol use, mental health, drug use, housing problems, violence in relationships, and legal problems. CONCLUSIONS: Evaluating the experiences of key communities in HIV prevention research can help identify barriers and facilitators to clinical trials engagement and improve the design of future trials.

Supporting the Art: Medication Adherence Patterns in Persons Prescribed Ingestible Sensor-enabled Oral Pre-Exposure Prophylaxis to Prevent Human Immunodeficiency Virus Infection.

BACKGROUND: Timely, accurate adherence data may support oral pre-exposure prophylaxis (PrEP) success and inform prophylaxis choice. We evaluated a Food and Drug Administration (FDA)-approved digital health feedback system (DHFS) with ingestible-sensor-enabled (IS) tenofovir-disoproxil-fumarate plus emtricitabine (Truvada®) in persons starting oral PrEP. METHODS: Human immunodeficiency virus (HIV)-negative adults were prescribed IS-Truvada® with DHFS for 12 weeks to observe medication taking behavior. Baseline demographics, urine toxicology, and self-report questionnaires were obtained. Positive detection accuracy and adverse events were computed as percentages, with Kaplan Meier Estimate for persistence-of-use. In participants persisting ≥28 days, adherence patterns (taking and timing) were analyzed, and mixed-effects logistic regression modeled characteristics associated with treatment adherence. RESULTS: Seventy-one participants were enrolled, mean age 37.6 years (range 18-69), 90.1% male, 77.5% White, 33.8% Hispanic, 95.8% housed, and 74.6% employed. Sixty-three participants (88.7%) persisted ≥28 days, generating 4987 observation days, average 79.2 (29-105). Total confirmed doses were 86.2% (95% confidence interval [CI] 82.5, 89.4), decreasing over time, odds ratio (OR) 0.899 (95% CI .876, .923) per week, P < .001; 79.4% (95% CI 66.7%, 87.3%) of participants had ≥80% adherence. Pattern analysis showed days without confirmed doses clustered (P = .003); regular dose timing was higher among participants with ≥80% confirmed doses (0.828, 95% CI .796 to .859) than among those with <80% (0.542, 95% CI95 .405 to .679) P < .001. In multi-predictor models, better adherence was associated with older age, OR 1.060 (95% CI 1.033, 1.091) per year, P < .001; negative vs positive methamphetamine screen, OR 5.051 (95% CI 2.252, 11.494), P < .001. CONCLUSIONS: DHFS with IS-Truvada® distinguished adherent persons from those potentially at risk of prophylactic failure. Ongoing methamphetamine substance use may impact oral PrEP success.

Estimated changes in price discounts for tenofovir-inclusive HIV treatments following introduction of tenofovir alafenamide.

We estimated list and net prices for tenofovir disoproxil fumarate (TDF) products Truvada, Complera, and Stribild, and their tenofovir alafenamide (TAF) versions Descovy, Odefsey, and Genvoya. Gilead offered discounts for Descovy that resulted into lower net prices compared to Truvada. This strategy encouraged patients switching from Truvada to Descovy before the availability of generic Truvada. Conversely, Gilead offered lower discounts for Odefsey and Genvoya, which resulted into higher net prices compared to Complera and Stribild.

The Elegance of the Acyclic Nucleoside Phosphonates (ANPs), Honorary Tribute to Antonín Holý, Who Passed Away on 16 July 2012, at the 10th Anniversary of His Death.

My collaboration with Prof. Antonín Holý, that spans a period of 3-4 decades (1976-2012), led to the discovery of several acyclic nucleoside phosphonates (ANPs) which were clinically developed by Gilead Sciences: cidofovir, adefovir, and tenofovir. The latter was further converted to two orally bioavailable prodrug forms, TDF and TAF, and both TDF and TAF were further combined with other antiviral drugs, thus giving rise to a broad array of antiviral drug combinations for the treatment of HIV infections. TDF and TAF are both available for the treatment of hepatitis B virus (HBV) infections, and, in combination with emtricitabine, also applicable as Truvada® and Descovy®, respectively, for the prophylaxis of HIV infections.

Comparison of the efficacy, safety and durability of a switch to co-formulated RPV/TDF-TAF/FTC or DTG/ABC/3TC in virologically-suppressed HIV-1-infected patients in a single Italian centre: a cohort data analysis.

This study evaluated the efficacy, safety and durability of a switch to co-formulated RPV/TDF-TAF/FTC (RPV-STR) or DTG/ABC/3TC (DTG-STR) in virologically-suppressed HIV-positive patients in a single Italian centre. All HIV-infected ART-experienced patients switching to RPV-STR or DTG-STR with HIV-RNA <50 copies/mL were included. Outcomes were incidence rate and rate ratios for discontinuation due to all causes (DAC), to adverse events (DAE) and to virological failure (VF) after 4 years of follow-up. We included 402 patients (244 on RPV-STR, 158 on DTG-STR). At Year 4 of follow-up, 124 patients (30.8%) discontinued for any cause (71 on RPV-STR, 53 on DTG-STR). Fifteen patients experienced VF [13 (5.3%) on RPV-STR and 2 (1.3%) on DTG-STR; log-rank, P = 0.4413]. Overall, 46 patients (11.4%) had AEs (23 on RPV-STR, 23 on DTG-STR). Nausea/diarrhoea was more frequent with DTG-STR (4.4% vs. 0%) and neurological toxicity with RPV-STR (4.5% vs. 2.5%). The rate of DAC within the first 3 months was significantly higher with DTG-STR (aRR = 5.88, 95% CI 3.20-10.81; P < 0.001); similarly, the discontinuation rate due to AEs was significantly higher with DTG-STR compared with RPV-STR (aRR = 12.89, 95% CI 5.48-30.32; P < 0.001). No difference in VF was observed between the two groups (RR = 0.47, 95% CI 0.10-2.14; P = 0.335). Patients with undetectable viral load who switched to DTG-STR or RPV-STR maintained virological suppression with a low risk of VF. A higher discontinuation rate was observed with DTG-STR compared with RPV-STR, particularly within 3 months from switch.

Tribute to John C. Martin at the Twentieth Anniversary of the Breakthrough of Tenofovir in the Treatment of HIV Infections.

At Bristol-Myers (BM) (1985-1990), John C. Martin started his HIV career with directing the clinical development of didanosine (ddI) and stavudine (d4T). During this period, he became aware of the acyclic nucleoside phosphonates (ANPs), such as (S)-HPMPA and PMEA, as potential antiviral drugs. Under his impulse, BM got involved in the evaluation of these ANPs, but the merger of BM with Squibb (to become BMS) incited John to leave BM and join Gilead Sciences, and the portfolio of the ANPs followed the transition. At Gilead, John succeeded in obtaining the approval from the US FDA for the use of cidofovir in the treatment of cytomegalovirus (CMV) retinitis in AIDS patients, which was reminiscent of John's first experience with ganciclovir (at Syntex) as an anti-CMV agent. At Gilead, John would then engineer the development of tenofovir, first as TDF (tenofovir disoproxil fumarate) and then as TAF (tenofovir alafenamide) and various combinations thereof, for the treatment of HIV infections (i), TDF and TAF for the treatment of hepatitis B (HBV) infections (ii), and TDF and TAF in combination with emtricitabine for the prophylaxis of HIV infections (iii).

Why Are Patients Switching from Tenofovir Disoproxil Fumarate/Emtricitabine (Truvada) to Tenofovir Alafenamide/Emtricitabine (Descovy) for Pre-Exposure Prophylaxis?

Safety differences between tenofovir alafenamide/emtricitabine (TAF) and tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)-formulated pre-exposure prophylaxis (PrEP) appear to have little clinical significance for most PrEP users. Furthermore, generic TDF-formulated PrEP is projected to decrease the price of PrEP. Thus, efforts to shift PrEP users to TAF-formulated PrEP should be considered in light of their potential to undermine efforts to scale-up PrEP nationally. Data are taken from Together 5,000, a US national cohort study predominantly composed of cisgender gay and bisexual men. In 2019-2020, 5034 participants completed their 24-month assessment, which measured whether participants were switching from TDF (Truvada) to TAF (Descovy) for PrEP, and why. Of those reporting PrEP-use (n = 1009), 277 reported using Descovy for PrEP, and 223 provided a reason for switching to Descovy. A content analysis was used to code participant's reasons for switching. Over half (56%) of participants reported that their doctor recommended switching to Descovy. Without mentioning a provider recommendation, 32% of participants reported that perceived improved safety of Descovy, compared with Truvada, motivated their decision to change their prescription. Other factors cited included the smaller size of the pill and "newness" of Descovy. Further, several participants mentioned negative advertising about Truvada as rationale for switching. Although scientific consensus supports the safety of both TDF/FTC and TAF, our results suggest that current messaging through physicians and other sources have emphasized superior safety of TAF-implying that TDF/FTC may not be safe in the long term. Efforts to shift users onto TAF may undermine public perception of TDF-formulated PrEP.

The effectiveness of tenofovir-based pre-exposure prophylaxis for prevention of HIV acquisition among sub-Saharan African women at high risk: a systematic review.

INTRODUCTION: women in sub-Saharan Africa (SSA) are disproportionately affected by the HIV epidemic. In 2019, they constituted 59% of new infections; thus, they remain a key population for control. Public health interventions to prevent acquisition of HIV in this high-risk population are urgently needed. Tenofovir-based pre-exposure prophylaxis (TFV-PrEP) has been shown to reduce HIV infections in other key populations. However, comprehensive evidence regarding TFV-PrEP effectiveness in women living in SSA has not been determined. Therefore, we undertook a systematic review to determine the effectiveness of tenofovir-1% (TFV-1%) vaginal gel, oral tenofovir (TFV) and tenofovir-emtricitabine (TDF-FTC) pre-exposure prophylaxis for primary acquisition of HIV in at-risk women living in SSA. METHODS: OVID Medline, Embase, CENTRAL, Web of Science and Clinical Trials.gov were searched for eligible studies from 1st January 2020 to 31st July 2020. Only randomised controlled trials (RCTs) conducted in women living in SSA were included. Measures of effectiveness (hazard ratios (HR), incidence rate ratios (IRR)) were extracted from individual studies to determine the effectiveness of TFV-PrEP in preventing HIV infection among at-risk women living in SSA. RESULTS: from 2002 non-duplicate articles, four RCTs evaluating the effectiveness of one or more of the interventions against placebos were included. TFV-1% vaginal gel, oral TDF or TDF-FTC were not effective in preventing the acquisition of HIV infection in women living in SSA. However, poor adherence by study participants could have confounded the true effectiveness of TFV-PrEP in this high risk population. Meta-analysis was not conducted given the limited number of eligible studies identified from the search. CONCLUSION: the current evidence does not support the effectiveness of TFV-PrEP for HIV in SSA women. More studies aimed at addressing factors driving low adherence to HIV interventions in this high risk population are urgently needed in order to improve the design of future RCTs leading to the determination of more reliable estimates of TFV-1% vaginal gel or oral TDF or TDF-FTC effectiveness. Protocol registration: this systematic review was not registered in PROSPERO.

Safety review of tenofovir disoproxil fumarate/emtricitabine pre-exposure prophylaxis for pregnant women at risk of HIV infection.

Introduction: Pregnancy is a period of elevated HIV risk in high-burden settings, motivating the need for prevention tools that are both safe for use and effective during pregnancy. Oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) is recommended by the World Health Organization, including for pregnant and postpartum women at substantial risk of HIV infection. Although TDF use during pregnancy appears generally safe, data on PrEP use during pregnancy remain limited.Areas covered: We provide an overview of the clinical pharmacology and efficacy of daily TDF-based PrEP and summarize current evidence on the safety of PrEP use by pregnant HIV-uninfected women. We synthesize relevant studies assessing pregnancy outcomes among pregnant women who are living with HIV (WLHIV) and using TDF-based therapy. Finally, we make comparison to the safety profiles of other emerging HIV prevention options.Expert opinion: The current evidence indicates that TDF/FTC PrEP use is not associated with increased risk of adverse pregnancy and early infant growth outcomes. While safety data are generally reassuring, there is need for continued accrual of data on growth and pregnancy outcomes in PrEP research, implementation projects, and controlled pharmacokinetic studies to support current evidence and to understand concentration-efficacy relationship in pregnant women.

Tenofovir and emtricitabine concentrations in hair are comparable between individuals on tenofovir disoproxil fumarate versus tenofovir alafenamide-based ART.

Tenofovir disoproxil fumarate (TDF) in combination with emtricitabine (FTC) is the backbone for both human immunodeficiency virus (HIV) treatment and pre-exposure prophylaxis (PrEP) worldwide. Tenofovir alafenamide (TAF) with FTC is increasingly used in HIV treatment and was recently approved for PrEP among men-who-have-sex-with-men. TDF and TAF are both metabolized into tenofovir (TFV). Antiretrovirals in plasma are taken up into hair over time, with hair levels providing a long-term measure of adherence. Here, we report a simple, robust, highly sensitive, and validated high-performance liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS)-based analytical method for analyzing TFV and FTC from individuals on either TDF/FTC or TAF/FTC in small hair samples. TFV/FTC are extracted from ~5 mg hair and separated on a column using a gradient elution. The lower quantification limits are 0.00200 (TFV) and 0.0200 (FTC) ng/mg hair; the assay is linear up to 0.400 (TFV) and 4.00 (FTC) ng/mg hair. The intra-day and inter-day coefficients of variance (CVs) are 5.39-12.6% and 6.40-13.5% for TFV and 0.571-2.45% and 2.45-5.16% for FTC. TFV concentrations from participants on TDF/FTC-based regimens with undetectable plasma HIV RNA were 0.0525 ± 0.0295 ng/mg, whereas those from individuals on TAF/FTC-based regimens were 0.0426 ± 0.0246 ng/mg. Despite the dose of TFV in TDF being 10 times that of TAF, hair concentrations of TFV were not significantly different for those on TDF versus TAF regimens. Pharmacological enhancers (ritonavir and cobicistat) did not boost TFV concentrations in hair. In summary, we developed and validated a sensitive analytical method to analyze TFV and FTC in hair and found that hair concentrations of TFV were essentially equivalent among those on TDF and TAF.

Primary HIV-1 infection in users of pre-exposure prophylaxis.

Pre-exposure prophylaxis (PrEP) has proven to be a highly effective and safe way to prevent HIV infection. Seroconversion and primary HIV infection are exceptional if adherence to PrEP is good. However, primary HIV infection while using PrEP can occur, albeit rarely, and HIV drug resistance might develop. Furthermore, the scope of PrEP is expected to expand, and clinicians might face potential seroconversions and primary HIV infection in patients starting or taking PrEP. The characteristics of primary HIV infection in users of PrEP are poorly described. PrEP users present a lower viral load peak during primary HIV infection and, frequently, fewer symptoms than individuals not exposed to PrEP. Additionally, PrEP prolongs the stages of seroconversion, thus potentially complicating diagnosis of primary HIV infection. Drug resistance is rare, occurring mostly when PrEP is initiated in undiagnosed patients who are at an extremely early stage of infection, in whom detection of HIV-RNA was not used to rule out HIV infection. Therefore, careful exclusion of primary HIV infection before starting PrEP is crucial. In patients presenting with primary HIV infection while on PrEP, a drug with a high genetic barrier (or even two) should be added to tenofovir disoproxil fumarate-emtricitabine until test results for resistance are available.

Effect of Truvada lawsuit advertising on preexposure prophylaxis attitudes and decisions among sexual and gender minority youth and young adults at risk for HIV.

OBJECTIVE: In 2019, US advocates reported misleading language regarding the safety of TDF/FTC (Truvada) used by lawsuit advertisements against Gilead Sciences. We sought to ascertain the reach and effects of the advertisements on preexposure prophylaxis (PrEP) opinions and decisions in a cohort of youth and young adults at-risk for HIV. DESIGN: An online survey was administered to participants enrolled in Keeping it LITE, a prospective US cohort study of ethnically diverse, sexually active, cisgender and transgender persons ages 13-37. METHODS: Quantitative data were analyzed using descriptive and inferential analysis in SAS, and qualitative data via thematic analysis. RESULTS: Survey response rate was 51.3% (n = 1485). Mean age at baseline was 24. Previous PrEP use was reported by 43% of respondents and 32.7% reported PrEP use in the past 6 months. Almost half (48.7%) were aware of the lawsuit. Most of these participants (81.3%) reported the advertisements did not impact their PrEP use, but 13.2% decided to not to begin a Truvada-based PrEP regimen and 5.5% decided to stop taking Truvada due to the advertisements claims. Predictors of changing PrEP behavior were lower education and no previous PrEP use. The qualitative analysis revealed the advertisements increased skepticism about safety and benefit of Truvada PrEP and led to greater distrust of the pharmaceutical industry. CONCLUSION: The advertisements reached a large, diverse US audience. Disturbingly, 18.7% of PrEP candidates who were aware of the lawsuit attributed not initiating or cessation of a Truvada-based PrEP regimen to exposure to the Truvada lawsuit advertisements.