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.

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.

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.

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.

Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa.

BACKGROUND: The World Health Organisation recommends the use of tenofovir-containing pre-exposure prophylaxis (PrEP) as an additional Human Immunodeficiency Virus (HIV) prevention choice for men and women at substantial risk of HIV infection. PrEP could fill an important HIV prevention gap, especially for sexually active young women who are limited in their ability to negotiate mutual monogamy or condom use. As PrEP is scaled up in high HIV incidence settings, it is crucial to consider the importance of early identification of HIV infection during PrEP use, to allow for rapid discontinuation of PrEP to reduce the risk of antiretroviral (ARV) resistance. The purpose of this case study is to provide this critical evidence. CASE PRESENTATION: This report describes a 20-year-old woman in a HIV sero-discordant relationship who initiated oral PrEP (tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC)) through a demonstration project (CAPRISA 084) in October 2017. Despite good adherence throughout her PrEP use, she tested HIV antibody positive at month nine of study participation. Retrospective testing showed increasing HIV viral load over time, and retrospective use of fourth-generation rapid HIV tests showed HIV detection (positive antigen/antibody) at month one. Sequencing confirmed a dominant wild type at month one with dual therapy resistance patterns emerging by month three (M184V and K65R mutations), which is suggestive of protracted PrEP use during an undetected HIV infection. The participant was referred to infectious diseases for further management of her HIV infection and was initiated on a first line, tenofovir-sparing regimen. At the time of this report (January 2020), the participant had been on ARV- therapy (ART) for 13 months and had no signs of either clinical, immunologic or virologic failure. CONCLUSIONS: This case report highlights the importance of appropriate HIV screening during wider oral PrEP scale-up in high HIV incidence settings to circumvent the consequences of prolonged dual therapy in an undiagnosed HIV infection and in turn prevent ARV resistance.

Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial.

BACKGROUND: Tenofovir alafenamide shows high antiviral efficacy and improved renal and bone safety compared with tenofovir disoproxil fumarate when used for HIV treatment. Here, we report primary results from a blinded phase 3 study evaluating the efficacy and safety of pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir alafenamide versus emtricitabine and tenofovir disoproxil fumarate for HIV prevention. METHODS: This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in regions of Europe and North America, where there is a high incidence of HIV or prevalence of people living with HIV, or both. We enrolled adult cisgender men who have sex with men and transgender women who have sex with men, both with a high risk of acquiring HIV on the basis of their self-reported sexual behaviour in the past 12 weeks or their recent history (within 24 weeks of enrolment) of bacterial sexually transmitted infections. Participants with current or previous use of PrEP with emtricitabine and tenofovir disoproxil fumarate were not excluded. We used a computer-generated random allocation sequence to randomly assign (1:1) participants to receive either emtricitabine (200 mg) and tenofovir alafenamide (25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine (200 mg) and tenofovir disoproxil fumarate (300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). As such, all participants were given two tablets. The trial sponsor, investigators, participants, and the study staff who provided the study drugs, assessed the outcomes, and collected the data were masked to group assignment. The primary efficacy outcome was incident HIV infection, which was assessed when all participants had completed 48 weeks of follow-up and half of all participants had completed 96 weeks of follow-up. This full analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug and had at least one post-baseline HIV test. Non-inferiority of emtricitabine and tenofovir alafenamide to emtricitabine and tenofovir disoproxil fumarate was established if the upper bound of the 95·003% CI of the HIV incidence rate ratio (IRR) was less than the prespecified non-inferiority margin of 1·62. We prespecified six secondary bone mineral density and renal biomarker safety endpoints to evaluate using the safety analysis set. This analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02842086, and is no longer recruiting. FINDINGS: Between Sept 13, 2016, and June 30, 2017, 5387 (92%) of 5857 participants were randomly assigned and received emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693). At the time of the primary efficacy analysis (ie, when all participants had completed 48 weeks and 50% had completed 96 weeks) emtricitabine and tenofovir alafenamide was non-inferior to emtricitabine and tenofovir disoproxil fumarate for HIV prevention, as the upper limit of the 95% CI of the IRR, was less than the prespecified non-inferiority margin of 1·62 (IRR 0·47 [95% CI 0·19-1·15]). After 8756 person-years of follow-up, 22 participants were diagnosed with HIV, seven participants in the emtricitabine and tenofovir alafenamide group (0·16 infections per 100 person-years [95% CI 0·06-0·33]), and 15 participants in the emtricitabine and tenofovir disoproxil fumarate group (0·34 infections per 100 person-years [0·19-0·56]). Both regimens were well tolerated, with a low number of participants reporting adverse events that led to discontinuation of the study drug (36 [1%] of 2694 participants in the emtricitabine and tenofovir alafenamide group vs 49 [2%] of 2693 participants in the emtricitabine and tenofovir disoproxil fumarate group). Emtricitabine and tenofovir alafenamide was superior to emtricitabine and tenofovir disoproxil fumarate in all six prespecified bone mineral density and renal biomarker safety endpoints. INTERPRETATION: Daily emtricitabine and tenofovir alafenamide shows non-inferior efficacy to daily emtricitabine and tenofovir disoproxil fumarate for HIV prevention, and the number of adverse events for both regimens was low. Emtricitabine and tenofovir alafenamide had more favourable effects on bone mineral density and biomarkers of renal safety than emtricitabine and tenofovir disoproxil fumarate. FUNDING: Gilead Sciences.

Long-Acting Cabotegravir Protects Macaques Against Repeated Penile Simian-Human Immunodeficiency Virus Exposures.

We used a novel penile simian-human immunodeficiency virus (SHIV) transmission model to investigate whether long-acting cabotegravir (CAB LA) prevents penile SHIV acquisition in macaques. Twenty-two macaques were exposed to SHIV via the foreskin and urethra once weekly for 12 weeks. Of these, 6 received human-equivalent doses of CAB LA, 6 received oral emtricitabine/tenofovir disoproxil fumarate, and 10 were untreated. The efficacy of CAB LA was high (94.4%; 95% confidence interval, 58.2%-99.3%) and similar to that seen with oral emtricitabine/tenofovir disoproxil fumarate (94.0%; 55.1%-99.2%). The high efficacy of CAB LA in the penile transmission model supports extending the clinical advancement of CAB LA preexposure prophylaxis to heterosexual men.

The HIV Pre-exposure Prophylaxis (PrEP) Cascade at NYC Sexual Health Clinics: Navigation Is the Key to Uptake.

BACKGROUND: Clinics providing sexual health care pose unique opportunities to implement HIV pre-exposure prophylaxis (PrEP) programs. The PrEP program at New York City's Sexual Health Clinics provides intensive on-site navigation for linkage to PrEP care. We assessed uptake of this intervention. METHODS: We categorized men who have sex with men (MSM) without HIV hierarchically as having had (1) HIV post-exposure prophylaxis (PEP) use (past year); or (2) selected sexually transmitted infections (STI) (past year); or (3) HIV-diagnosed sex/needle-sharing partners (past 6 months); or (4) expressed interest in PrEP (day of clinic visit). We constructed PrEP cascades and used multivariable regression to examine acceptance of PrEP navigation, referral to a PrEP provider, linkage (<60 days), and PrEP prescription. RESULTS: One thousand three hundred one of 2106 PrEP (62%) patients accepted navigation. Of those, 55% (718/1301) were black or Hispanic MSM. STI and PEP patients had lowest navigation acceptance levels (35%-46%). Of navigated patients, 56% (628/1114) accepted referrals, 46% (288/628) linked to PrEP providers, and 82% (235/288) were prescribed PrEP; overall, 11% of those offered navigation (235/2106) received prescriptions. Navigated MSM with PEP history [adjusted prevalence ratio (aPR) 1.34, 95% confidence interval (CI): 1.16 to 1.56)], previous STI (aPR 1.28, 95% CI: 1.12 to 1.45), or HIV-diagnosed partners (aPR 1.18, 95% CI: 1.01 to 1.37) were more likely than those with PrEP interest to accept referrals. Probability of linkage varied by insurance status; prescription did not vary by patient factors. CONCLUSIONS: Although MSM in key priority groups (eg, previous STI) showed low navigation uptake, those who accepted navigation were likely to be referred for PrEP, suggesting a need for expanded up-front engagement.

Atypical secondary syphilis presentation in a patient with human immunodeficiency virus infection: a case report.

INTRODUCTION: Untreated syphilis may lead to severe complications. This infection has recently re-emerged in developed countries with a high number of cases coinfected with human immunodeficiency virus. In these patients, the skin lesions of secondary syphilis can be very atypical. CASE PRESENTATION: We report the case of a 38-year-old Bulgarian homosexual man who was coinfected with human immunodeficiency virus and syphilis. His skin contained multiple extensive necrotic lesions with abundant purulent secretion that covered his face, lips, scalp, and torso. Initial clinical diagnoses included varicella pustulosa and staphylococcal dermatitis. Human immunodeficiency virus infection in our patient had been established 2 years earlier in prophylactic studies, but had not been treated. Due to lack of penicillin, he was successfully treated with ceftriaxone, and the skin lesions underwent complete reversal. He also began antiretroviral therapy, which resulted in a significant effect on his immune status. Three months after the onset of antiretroviral therapy, he also achieved optimal viral suppression. CONCLUSION: This case emphasizes the importance of considering cutaneous secondary syphilis in the differential diagnosis of any inflammatory cutaneous disorder in individuals infected with human immunodeficiency virus.

Piloting a partially self-financed mode of human immunodeficiency virus pre-exposure prophylaxis delivery for men who have sex with men in Hong Kong.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg is a proven strategy for preventing human immunodeficiency virus (HIV) transmission in men who have sex with men (MSM). This study aimed to test the feasibility and acceptability of PrEP delivered at a pilot clinic for MSM in Hong Kong, where PrEP service is currently unavailable. METHODS: Partially self-financed PrEP was provided to HIV-negative adult MSM with high behavioural risk of HIV transmission after excluding hepatitis B infection and renal insufficiency. Participants received daily TDF/FTC for 30 weeks at 13.3% of the drug cost. Adherence and behaviours were monitored through questionnaires while creatinine and HIV/STI (sexually transmitted infection) incidence were monitored with point-of-care and laboratory tests. Preference for continuing with PrEP was evaluated at the end of the prescription period. RESULTS: Seventy-one PrEP-naïve MSM were included in the study, of whom 57 (80%) were retained at the end of 28 weeks. Satisfactory adherence and self-limiting adverse events were reported, while none of the participants contracted HIV. Risk compensation was observed, with an STI incidence of 3.17 per 100 person-years. At the end of the prescription period, a majority (89%) indicated interest in continuing with PrEP. Preference for PrEP was associated with age ≥28 years and peer influence (P=0.04), while stigma was a concern. Price was a deterrent to self-financed PrEP, and only half (51%) considered a monthly cost of ≤HK$500 (US$1=HK$7.8) as reasonable. CONCLUSIONS: A partially self-financed mode of PrEP delivery is feasible with good retention in MSM in Hong Kong.

Performance of HIV pre-exposure prophylaxis indirect adherence measures among men who have sex with men and transgender women: Results from the PrEP Brasil Study.

INTRODUCTION: Efficacy of daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) for PrEP is strongly dependent on the adherence. We examined the concordance between indirect adherence measures and protective drug levels among participants retained through 48 weeks in the PrEP Brasil Study. METHODS: PrEP Brasil was a prospective, multicenter, open-label demonstration project evaluating PrEP provision for men who have sex with men (MSM) and transgender women (TGW) at higher risk for HIV infection within the setting of Brazilian Public Health System. Three indirect adherence measures were obtained at week 48: medication possession ratio (MPR), pill count and self-report (30-days recall). Tenofovir diphosphate (TFV-DP) concentration in Dried Blood Spot (DBS) was measured at week 48. Areas under (AUC) the receiver operating characteristics (ROC) curve were used to evaluate the concordance between achieving protective drug levels (TFV-DP≥700fmol/punch) and the indirect adherence measures. Youden's index and distance to corner were used to determine the optimal cutoff points for each indirect adherence measure. We calculated sensitivity, specificity, negative (NPV) and positive (PPV) predictive values for the found cutoff points. Finally, Delong test was used to compare AUCs. RESULTS AND DISCUSSION: From April, 2014 to July, 2016, 450 participants initiated PrEP, 375(83.3%) were retained through 48 weeks. Of these, 74% (277/375) had TFV-DP ≥700fmol/punch. All adherence measures discriminated between participants with and without protective drug levels (AUC>0.5). High indirect adherence measure was predictive of protective drug levels (PPV>0.8) while low indirect adherence measure was not predictive of lack of protective drug levels (NPV<0.5). No significant differences were found between the adherence methods (p = 0.44). CONCLUSIONS: Low-burden measurements such as MPR and self-report can be used to predict PrEP adherence in a public health context in Brazil for MSM and TGW retained through 48 weeks. Clinical Trial Number: NCT01989611.

Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52-96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.