1,116 results on '"Anderson, Peter L."'
Search Results
2. The Effect of Disclosure of PrEP Use on Adherence Among African Young Women in an Open-Label PrEP Study: Findings from HPTN 082
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Beauchamp, Geetha, Hosek, Sybil, Donnell, Deborah, Chan, Kwun C. G., Anderson, Peter L., Dye, Bonnie J., Mgodi, Nyaradzo, Bekker, Linda-Gail, Delany-Moretlwe, Sinead, and Celum, Connie
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- 2024
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3. Efficacy and safety of long-acting cabotegravir compared with daily oral tenofovir disoproxil fumarate plus emtricitabine to prevent HIV infection in cisgender men and transgender women who have sex with men 1 year after study unblinding: a secondary analysis of the phase 2b and 3 HPTN 083 randomised controlled trial
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Landovitz, Raphael J, Hanscom, Brett S, Clement, Meredith E, Tran, Ha V, Kallas, Esper G, Magnus, Manya, Sued, Omar, Sanchez, Jorge, Scott, Hyman, Eron, Joe J, del Rio, Carlos, Fields, Sheldon D, Marzinke, Mark A, Eshleman, Susan H, Donnell, Deborah, Spinelli, Matthew A, Kofron, Ryan M, Berman, Richard, Piwowar-Manning, Estelle M, Richardson, Paul A, Sullivan, Philip A, Lucas, Jonathan P, Anderson, Peter L, Hendrix, Craig W, Adeyeye, Adeola, Rooney, James F, Rinehart, Alex R, Cohen, Myron S, McCauley, Marybeth, Grinsztejn, Beatriz, and Team, HPTN 083 Study
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Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,Minority Health ,Women's Health ,Sexually Transmitted Infections ,HIV/AIDS ,Health Disparities ,Prevention ,Sexual and Gender Minorities (SGM/LGBT*) ,Behavioral and Social Science ,Clinical Research ,Clinical Trials and Supportive Activities ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Male ,Female ,Humans ,Adolescent ,HIV Infections ,Tenofovir ,Emtricitabine ,Anti-HIV Agents ,Transgender Persons ,Retrospective Studies ,HIV-1 ,Acquired Immunodeficiency Syndrome ,Pre-Exposure Prophylaxis ,HPTN 083 Study Team ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundInjectable cabotegravir was superior to daily oral tenofovir disoproxil fumarate plus emtricitabine for HIV prevention in two clinical trials. Both trials had the primary aim of establishing the HIV prevention efficacy of long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) compared with tenofovir disoproxil fumarate plus emtricitabine daily oral PrEP. Long-acting PrEP was associated with diagnostic delays and integrase strand-transfer inhibitor (INSTI) resistance. This report presents findings from the first unblinded year of the HIV Prevention Trials Network (HPTN) 083 study.MethodsThe HPTN 083 randomised controlled trial enrolled HIV-uninfected cisgender men and transgender women at elevated HIV risk who have sex with men, from 43 clinical research sites in Africa, Asia, Latin America, and the USA. Inclusion criteria included: a negative HIV serological test at the screening and study entry, undetectable HIV RNA levels within 14 days of study entry, age 18 years or older, overall good health as determined by clinical and laboratory evaluations, and a creatinine clearance of 60 mL/min or higher. Participants were randomly allocated to receive long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP. After study unblinding, participants remained on their original regimen awaiting an extension study. HIV infections were characterised retrospectively at a central laboratory. Here we report the secondary analysis of efficacy and safety for the first unblinded year. The primary outcome was incident HIV infection. Efficacy analyses were done on the modified intention-to-treat population using a Cox regression model. Adverse events were compared across treatment groups and time periods (blinded vs unblinded). This trial is registered with ClinicalTrials.gov, NCT02720094.FindingsOf the 4488 participants who contributed person-time to the blinded analysis, 3290 contributed person-time to the first unblinded year analysis between May 15, 2020, and May 14, 2021. Updated HIV incidence in the blinded phase was 0·41 per 100 person-years for long-acting injectable cabotegravir PrEP and 1·29 per 100 person-years for daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP (hazard ratio [HR] 0·31 [95% CI 0·17-0·58], p=0·0003). HIV incidence in the first unblinded year was 0·82 per 100 person-years for long-acting PrEP and 2·27 per 100 person-years for daily oral PrEP (HR 0·35 [0·18-0·69], p=0·002). Adherence to both study products decreased after study unblinding. Additional infections in the long-acting PrEP group included two with on-time injections; three with one or more delayed injections; two detected with long-acting PrEP reinitiation; and 11 more than 6 months after their last injection. Infection within 6 months of cabotegravir exposure was associated with diagnostic delays and INSTI resistance. Adverse events were generally consistent with previous reports; incident hypertension in the long-acting PrEP group requires further investigation.InterpretationLong-acting injectable cabotegravir PrEP retained high efficacy for HIV prevention in men and transgender women who have sex with men during the first year of open-label follow-up, with a near-identical HR for HIV risk reduction between long-acting injectable cabotegravir and daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP during the first year after unblinding compared with the blinded period. Extended follow-up further defined the risk period for diagnostic delays and emergence of INSTI resistance.FundingDivision of AIDS at the National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and Gilead Sciences.
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- 2023
4. Viral and host mediators of non-suppressible HIV-1 viremia
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Mohammadi, Abbas, Etemad, Behzad, Zhang, Xin, Li, Yijia, Bedwell, Gregory J, Sharaf, Radwa, Kittilson, Autumn, Melberg, Meghan, Crain, Charles R, Traunbauer, Anna K, Wong, Colline, Fajnzylber, Jesse, Worrall, Daniel P, Rosenthal, Alex, Jordan, Hannah, Jilg, Nikolaus, Kaseke, Clarety, Giguel, Francoise, Lian, Xiaodong, Deo, Rinki, Gillespie, Elisabeth, Chishti, Rida, Abrha, Sara, Adams, Taylor, Siagian, Abigail, Dorazio, Dominic, Anderson, Peter L, Deeks, Steven G, Lederman, Michael M, Yawetz, Sigal, Kuritzkes, Daniel R, Lichterfeld, Mathias D, Sieg, Scott, Tsibris, Athe, Carrington, Mary, Brumme, Zabrina L, Castillo-Mancilla, Jose R, Engelman, Alan N, Gaiha, Gaurav D, and Li, Jonathan Z
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Clinical Research ,HIV/AIDS ,Infectious Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Infection ,Humans ,Male ,Female ,HIV-1 ,Viremia ,Proviruses ,HIV Seropositivity ,HIV Infections ,CD4-Positive T-Lymphocytes ,RNA ,Viral ,Viral Load ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level viremia on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding of HIV-1 persistence. Here we analyzed plasma virus sequences in eight ART-treated individuals with NSV (88% male) and show that they are composed of large clones without evidence of viral evolution over time in those with longitudinal samples. We defined proviruses that match plasma HIV-1 RNA sequences as 'producer proviruses', and those that did not as 'non-producer proviruses'. Non-suppressible viremia arose from expanded clones of producer proviruses that were significantly larger than the genome-intact proviral reservoir of ART-suppressed individuals. Integration sites of producer proviruses were enriched in proximity to the activating H3K36me3 epigenetic mark. CD4+ T cells from participants with NSV demonstrated upregulation of anti-apoptotic genes and downregulation of pro-apoptotic and type I/II interferon-related pathways. Furthermore, participants with NSV showed significantly lower HIV-specific CD8+ T cell responses compared with untreated viremic controllers with similar viral loads. We identified potential critical host and viral mediators of NSV that may represent targets to disrupt HIV-1 persistence.
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- 2023
5. Extended Analysis of HIV Infection in Cisgender Men and Transgender Women Who Have Sex with Men Receiving Injectable Cabotegravir for HIV Prevention: HPTN 083
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Marzinke, Mark A, Fogel, Jessica M, Wang, Zhe, Piwowar-Manning, Estelle, Kofron, Ryan, Moser, Amber, Bhandari, Pradip, Gollings, Ryann, Bushman, Lane R, Weng, Lei, Halvas, Elias K, Mellors, John, Anderson, Peter L, Persaud, Deborah, Hendrix, Craig W, McCauley, Marybeth, Rinehart, Alex R, St Clair, Marty, Ford, Susan L, Rooney, James F, Adeyeye, Adeola, Chariyalertsak, Suwat, Mayer, Kenneth, Arduino, Roberto C, Cohen, Myron S, Grinsztejn, Beatriz, Hanscom, Brett, Landovitz, Raphael J, and Eshleman, Susan H
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Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,Prevention ,Sexual and Gender Minorities (SGM/LGBT*) ,HIV/AIDS ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Male ,Humans ,Female ,HIV Infections ,Anti-HIV Agents ,Transgender Persons ,Retrospective Studies ,Tenofovir ,Emtricitabine ,Pre-Exposure Prophylaxis ,HIV ,preexposure prophylaxis ,prevention ,cabotegravir ,injectable ,TDF-FTC ,long-acting ,men who have sex with men ,HPTN 083 ,Microbiology ,Medical Microbiology ,Pharmacology and Pharmaceutical Sciences ,Medical microbiology ,Pharmacology and pharmaceutical sciences - Abstract
HPTN 083 demonstrated that injectable cabotegravir (CAB) was superior to oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for HIV prevention in cisgender men and transgender women who have sex with men. We previously analyzed 58 infections in the blinded phase of HPTN 083 (16 in the CAB arm and 42 in the TDF-FTC arm). This report describes 52 additional infections that occurred up to 1 year after study unblinding (18 in the CAB arm and 34 in the TDF-FTC arm). Retrospective testing included HIV testing, viral load testing, quantification of study drug concentrations, and drug resistance testing. The new CAB arm infections included 7 with CAB administration within 6 months of the first HIV-positive visit (2 with on-time injections, 3 with ≥1 delayed injection, and 2 who restarted CAB) and 11 with no recent CAB administration. Three cases had integrase strand transfer inhibitor (INSTI) resistance (2 with on-time injections and 1 who restarted CAB). Among 34 CAB infections analyzed to date, diagnosis delays and INSTI resistance were significantly more common in infections with CAB administration within 6 months of the first HIV-positive visit. This report further characterizes HIV infections in persons receiving CAB preexposure prophylaxis and helps define the impact of CAB on the detection of infection and the emergence of INSTI resistance.
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- 2023
6. Performance of Multiple Adherence Measures for pre-exposure Prophylaxis (PrEP) Among Young Women in Kenya
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Musinguzi, Nicholas, Ngure, Kenneth, Bukusi, Elizabeth A., Mugo, Nelly R., Baeten, Jared M., Anderson, Peter L., and Haberer, Jessica E.
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- 2023
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7. Efficacy estimates of oral pre-exposure prophylaxis for HIV prevention in cisgender women with partial adherence
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Moore, Mia, Stansfield, Sarah, Donnell, Deborah J., Boily, Marie-Claude, Mitchell, Kate M., Anderson, Peter L., Delany-Moretlwe, Sinead, Bekker, Linda-Gail, Mgodi, Nyaradzo M., Celum, Connie L., and Dimitrov, Dobromir
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- 2023
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8. Randomized Trial of Individualized Texting for Adherence Building (iTAB) Plus Motivational Interviewing for PrEP Adherence in Transgender Individuals: The iM-PrEPT Study
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Morris, Sheldon R, Jain, Sonia, Blumenthal, Jill, Bolan, Robert, Dubé, Michael P, Henderson, Philip, Corado, Katya, Sun, Shelly, He, Feng, Chow, Karen, Burke, Leah, Anderson, Peter L, and Moore, David J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Behavioral and Social Science ,Clinical Research ,Prevention ,Clinical Trials and Supportive Activities ,Good Health and Well Being ,Male ,Female ,Humans ,Transgender Persons ,Text Messaging ,Anti-HIV Agents ,Motivational Interviewing ,HIV Infections ,Medication Adherence ,Pre-Exposure Prophylaxis ,Emtricitabine ,transgender ,HIV prevention ,text messaging ,intervention ,PrEP ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundTransgender and nonbinary individuals at risk for HIV may benefit from adherence support for pre-exposure prophylaxis.MethodsBetween June 2017 and September 2020, 255 transgender and nonbinary individuals received daily oral tenofovir disoproxil fumarate/emtricitabine for 48 weeks randomized 1:1 to receive individualized Texting for Adherence Building (iTAB) or iTAB plus motivational interviewing (iTAB + MI) through phone for nonadherence. The primary end point was dried blood spot tenofovir diphosphate concentrations at weeks 12 and 48 (or last on-drug study visit) ≥1246 fmol/punch consistent with ≥7 doses/week (ie, near-perfect adherence). Secondary outcomes included dried blood spot tenofovir diphosphate concentrations ≥719 fmol/punch consistent with ≥4 doses/week (ie, adequate adherence) and self-reported adherence by daily text messages.ResultsAdherence for the outcome ≥1246 fmol/punch and ≥719 fmol/punch, respectively, was 49.1% and 57.9% for transgender men, 37.7% and 47.2% for nonbinary individuals, and 31.0% and 44.1% for transgender women. No difference was seen in iTAB + MI compared with iTAB alone by drug levels except where it approached significance in transgender women for the outcome of ≥719 fmol/punch in the iTAB + MI group compared with iTAB only (52% versus 35.7%, P = 0.065). There was a significant difference in self-reported daily dose adherence in the iTAB + MI group compared with iTAB alone (57.9% of days versus 46.4%, P = 0.009). In transgender women, the mean percentage of daily doses taken was 58.5% with iTAB + MI and 37.3% with iTAB alone ( P < 0.001).ConclusionsIn addition to automated approaches to adherence promotion, phone-based MI triggered by repeatedly missing doses may improve pre-exposure prophylaxis adherence among transgender women.
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- 2022
9. Gender-Affirming Hormone Pharmacokinetics Among Adolescent and Young Adult Transgender Persons Receiving Daily Emtricitabine/Tenofovir Disoproxil Fumarate
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Yager, Jenna, Brooks, Kristina M, Brothers, Jennifer, Mulligan, Kathleen, Landovitz, Raphael J, Reirden, Daniel, Malhotra, Meenakshi, Glenny, Carrie, Harding, Paul, Powell, Tina, Anderson, Peter L, and Hosek, Sybil
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Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,HIV/AIDS ,Sexual and Gender Minorities (SGM/LGBT*) ,Clinical Research ,Clinical Trials and Supportive Activities ,Women's Health ,Sexually Transmitted Infections ,Adolescent ,Adult ,Female ,Humans ,Male ,Young Adult ,Anti-HIV Agents ,Emtricitabine ,Estradiol ,HIV Infections ,Pre-Exposure Prophylaxis ,Reverse Transcriptase Inhibitors ,Tenofovir ,Testosterone ,Transgender Persons ,PrEP ,transgender women ,transgender men ,estradiol ,testosterone ,GAHT ,Virology ,Clinical sciences - Abstract
Transgender persons have an increased vulnerability to HIV infection yet have not been well-represented in past clinical trials for pre-exposure prophylaxis (PrEP). Because of this, there are few data available to understand whether gender-affirming hormone concentrations are influenced by PrEP agents in transgender men (TM) and transgender women (TW). The objective of this study was to compare gender-affirming hormone concentrations with versus without emtricitabine (F, FTC)-tenofovir disoproxil fumarate (TDF). TM and TW without HIV, aged 15-24 years, were enrolled for 1 month of directly observed daily F/TDF. Participants were required to be receiving a stable hormone dose (estradiol or testosterone) for at least 1 month or three consecutive doses, whichever was longer, before enrollment and willing to continue the same dose. Intensive pharmacokinetic (PK) sampling for gender-affirming hormones was collected before and 2-3 weeks after daily F/TDF. Serum estradiol and total testosterone were determined by liquid chromatography-tandem mass spectrometry; free testosterone by equilibrium dialysis. Maximum concentrations (Cmax) and area under the curve (AUClast) were log-transformed and compared between baseline and on F/TDF using geometric mean ratios (GMRs) with 95% confidence intervals (CIs). Twenty-five TW and 24 TM were enrolled (median age: 20 and 21 years, respectively). In TW, estradiol Cmax (GMR [95% CI]: 0.85 [0.65-1.11]) and AUClast (GMR [95% CI]: 0.87 [0.73-1.03]) were comparable on F/TDF versus baseline. In TM, similar comparability was observed for PrEP versus baseline including total testosterone Cmax (GMR [95% CI]: 0.91 [0.80-1.03]) and AUClast (GMR [95% CI]: 0.91 [0.81-1.04]) and free testosterone Cmax (GMR [95% CI]: 0.89 [0.74-1.07]) and AUClast (GMR [95% CI]: 0.88 [0.74-1.03]). Estradiol and testosterone exposures in young TW and TM did not significantly differ on F/TDF versus baseline. These findings should reassure patients and providers that F/TDF can be used as PrEP without concern for altering gender-affirming hormone PK. ClinicalTrials.gov (NCT03652623).
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- 2022
10. Pharmacokinetics of Emtricitabine/Tenofovir Disoproxil Fumarate Among Transgender Adolescents and Young Adults Without HIV Receiving Gender Affirming Hormones
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Yager, Jenna, Brooks, Kristina M, Brothers, Jennifer, Mulligan, Kathleen, Landovitz, Raphael, Reirden, Daniel, Glenny, Carrie, Malhotra, Meena, Anderson, Peter L, and Hosek, Sybil
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Women's Health ,Health Disparities ,Sexual and Gender Minorities (SGM/LGBT*) ,HIV/AIDS ,Sexually Transmitted Infections ,Infectious Diseases ,6.1 Pharmaceuticals ,Male ,Young Adult ,Adolescent ,Female ,Humans ,Transgender Persons ,Anti-HIV Agents ,Leukocytes ,Mononuclear ,Prospective Studies ,HIV Infections ,Emtricitabine ,Tenofovir ,Pre-Exposure Prophylaxis ,Reverse Transcriptase Inhibitors ,Hormones ,transgender women ,transgender men ,PrEP ,pharmacology ,F ,TDF ,F/TDF ,Virology ,Clinical sciences - Abstract
The transgender community has expressed concerns regarding drug-drug interactions between HIV-pre-exposure prophylaxis (PrEP) and gender-affirming hormones. In this study, we evaluated emtricitabine (F, FTC)/tenofovir (TFV) disoporoxil fumarate (TDF) pharmacokinetics (PK) among adolescent and young adult transgender persons receiving gender-affirming hormone therapy (GAHT). This was a prospective, observational study among transgender women (TW) and men (TM) without HIV, 15-24 years of age, receiving GAHT (estradiol with/without spironolactone, or testosterone). Participants received 1 month of directly observed daily F/TDF. Weekly convenience blood samples were collected for plasma TFV and FTC, and intracellular TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) in peripheral blood mononuclear cells (PBMC) and dried blood spots (DBS). After 2-3 weeks of F/TDF dosing, intensive PK sampling was conducted. PK parameters were estimated using noncompartmental methods. Data were log-transformed and compared between TM and TW, and to historical data among cisgender adults. Plasma TFV exposures were similar between TM and TW [geometric mean ratio (GMR); confidence interval (95% CI): 1.06 (0.89-1.28)], whereas FTC plasma exposures were 21% higher in TM versus TW (95% CI: 1.07-1.38). TFV-DP in PBMC and DBS and FTC-TP in DBS did not differ between TM versus TW after controlling for creatinine clearance (CrCl), but FTC-TP in PBMC remained 46% (95% CI: 1.15-1.86) higher in TM versus TW. All PK exposures were within expected ranges based on historical studies. TM had higher FTC exposures compared with TW, but overall plasma and intracellular exposures for both drugs were within the range of historical studies, suggesting high PrEP efficacy will be retained in adolescent and young adult transgender persons. Registered at ClinicalTrials.gov (NCT03652623).
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- 2022
11. Sexual behaviour and incidence of sexually transmitted infections among men who have sex with men (MSM) using daily and event-driven pre-exposure prophylaxis (PrEP): Four-year follow-up of the Amsterdam PrEP (AMPrEP) demonstration project cohort
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van den Elshout, Mark A. M., Wijstma, Eline S., Boyd, Anders, Jongen, Vita W., Coyer, Liza, Anderson, Peter L., Davidovich, Udi, de Vries, Henry J. C., Prins, Maria, Schim van der Loeff, Maarten F., and Hoornenborg, Elske
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Medical research ,Medicine, Experimental ,Sexually transmitted diseases -- Statistics -- Physiological aspects -- Drug therapy ,MSM (Men who have sex with men) -- Sexual behavior -- Health aspects -- Drug therapy ,Biological sciences - Abstract
Background An increasing number of countries are currently implementing or scaling-up HIV pre-exposure prophylaxis (PrEP) care. With the introduction of PrEP, there was apprehension that condom use would decline and sexually transmitted infections (STIs) would increase. To inform sexual health counselling and STI screening programmes, we aimed to study sexual behaviour and STI incidence among men who have sex with men (MSM) and transgender women who use long-term daily or event-driven PrEP. Methods and findings The Amsterdam PrEP demonstration project (AMPrEP) was a prospective, closed cohort study, providing oral daily PrEP and event-driven PrEP to MSM and transgender women from 2015 to 2020. Participants could choose their PrEP regimen and could switch at each three-monthly visit. STI testing occurred at and, upon request, in-between 3-monthly study visits. We assessed changes in numbers of sex partners and condomless anal sex (CAS) acts with casual partners over time using negative binomial regression, adjusted for age. We assessed HIV incidence and changes in incidence rates (IRs) of any STI (i.e., chlamydia, gonorrhoea, or infectious syphilis) and individual STIs over time using Poisson regression, adjusted for age and testing frequency. A total of 367 participants (365 MSM) commenced PrEP and were followed for a median 3.9 years (interquartile range [IQR] = 3.4-4.0). Median age was 40 years (IQR = 32-48), 315 participants (85.8%) self-declared ethnicity as white and 280 (76.3%) had a university or university of applied sciences degree. Overall median number of sex partners (past 3 months) was 13 (IQR = 6-26) and decreased per additional year on PrEP (adjusted rate ratio [aRR] = 0.86/year, 95% confidence interval [CI] = 0.83-0.88). Overall median number of CAS acts with casual partners (past 3 months) was 10 (IQR = 3-20.5) and also decreased (aRR = 0.92/year, 95% CI = 0.88-0.97). We diagnosed any STI in 1,092 consultations during 1,258 person years, resulting in an IR of 87/100 person years (95% CI = 82-92). IRs of any STI did not increase over time for daily PrEP or event-driven PrEP users. Two daily PrEP users, and no event-driven PrEP users, were diagnosed with HIV during their first year on PrEP. Study limitations include censoring follow-up due to COVID-19 measures and an underrepresentation of younger, non-white, practically educated, and transgender individuals. Conclusions In this prospective cohort with a comparatively long follow-up period of 4 years, we observed very low HIV incidence and decreases in the numbers of casual sex partners and CAS acts over time. Although the STI incidence was high, it did not increase over time. Trial registration The study was registered at the Netherlands Trial Register (NL5413) https://www.onderzoekmetmensen.nl/en/trial/22706, Author(s): Mark A. M. van den Elshout 1,*, Eline S. Wijstma 1, Anders Boyd 1,2,3,4, Vita W. Jongen 1,2, Liza Coyer 1, Peter L. Anderson 5, Udi Davidovich 1,6, Henry [...]
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- 2024
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12. Acceptability and Feasibility of Providing Adherence Feedback Based on Tenofovir Diphosphate in Dried Blood Spots: Results from a Pilot Study Among Patients and Providers in Cape Town, South Africa
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Ferraris, Christopher M., D’avanzo, Paul A., Jennings, Lauren, Robbins, Reuben N., Nguyen, Nadia, Leu, Cheng-Shiun, Dolezal, Curtis, Mgbako, Ofole, Hsiao, Nei-yuan, Joska, John, Castillo-mancilla, Jose R., Myer, Landon, Anderson, Peter L., Belaunzarán-zamudio, Pablo F., Mellins, Claude A., Orrell, Catherine, and Remien, Robert H.
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- 2023
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13. Concordance between daily diary reported pre-exposure prophylaxis intake and intraerythrocytic tenofovir diphosphate in the Amsterdam Pre-exposure Prophylaxis demonstration project
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Wijstma, Eline S., Jongen, Vita W., Boyd, Anders, van den Elshout, Mark A.M., de Vries, Henry J.C., Davidovich, Udi, Anderson, Peter L., Prins, Maria, Hoornenborg, Elske, and Schim van der Loeff, Maarten F.
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- 2024
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14. Hepatitis B virus (HBV) viremia despite tenofovir disoproxil fumarate-containing antiretroviral therapy in persons with HBV/HIV coinfection
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Ryan, Patrick, Odegard, Elizabeth, Meeds, Heidi, Lartey, Margaret, Ganu, Vincent J., Tachi, Kenneth, Yang, Hongmei, Ojewale, Oluwayemisi, Boamah, Isaac, Obo-Akwa, Adjoa, Antwi, Kenneth, Anderson, Peter L., Blackard, Jason T., and Kwara, Awewura
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- 2024
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15. Evaluation of pharmacokinetics of Tenofovir Alafenamide (TAF) and Tenofovir Disoproxil (TDF) in pregnant and postpartum women in South Africa: PrEP-PP PK study
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Joseph Davey, Dvora, Dadan, Sumaya, Bheemraj, Kalisha, Waitt, Catriona, Khoo, Saye, Myer, Landon, Wiesner, Lubbe, Else, Laura, Thompson, Beth, Castel, Sandra, Wara, Nafisa, Anderson, Peter L., and Orrell, Catherine
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- 2024
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16. Adults on pre-exposure prophylaxis (tenofovir-emtricitabine) have faster clearance of anti-HIV monoclonal antibody VRC01
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Huang, Yunda, Zhang, Lily, Karuna, Shelly, Andrew, Philip, Juraska, Michal, Weiner, Joshua A., Angier, Heather, Morgan, Evgenii, Azzam, Yasmin, Swann, Edith, Edupuganti, Srilatha, Mgodi, Nyaradzo M., Ackerman, Margaret E., Donnell, Deborah, Gama, Lucio, Anderson, Peter L., Koup, Richard A., Hural, John, Cohen, Myron S., Corey, Lawrence, McElrath, M. Juliana, Gilbert, Peter B., and Lemos, Maria P.
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- 2023
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17. Trust in the provider and accurate self-reported PrEP adherence among adolescent girls and young women in South Africa and Zimbabwe: HPTN 082 study
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Beauchamp, Geetha, Donnell, Deborah, Hosek, Sybil, Anderson, Peter L., Chan, Kwun C. G., Dye, Bonnie J., Mgodi, Nyaradzo, Bekker, Linda-Gail, Delany-Moretlwe, Sinead, and Celum, Connie
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- 2023
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18. Genital Inflammation Is Not Associated With Decreased Vaginal Tenofovir Concentrations in Women Taking Oral PrEP
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Morris, Sheldon, Cottrell, Mackenzie, Rawlings, Stephen A, Peterson, Scott, Karris, Maile, Pacheco, Deedee, Chaillon, Antoine, Kay, Alexis, Chow, Karen, Anderson, Peter L, Gianella, Sara, and Blumenthal, Jill
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Medical Microbiology ,Reproductive Medicine ,Biomedical and Clinical Sciences ,Clinical Sciences ,Sexually Transmitted Infections ,Infectious Diseases ,HIV/AIDS ,Clinical Research ,Topical Microbicides ,Behavioral and Social Science ,Health Disparities ,Women's Health ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Anti-HIV Agents ,Female ,HIV Infections ,Humans ,Inflammation ,Pre-Exposure Prophylaxis ,Tenofovir ,Vagina ,HIV pre-exposure prophylaxis ,women ,Gardnerella ,vaginal microbiome ,tenofovir ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundWe evaluated the association of inflammation and dysbosis on cervicovaginal fluid (CVF) tenofovir (TFV) concentrations in women taking oral tenofovir disoproxil fumarate/emtricitable for HIV pre-exposure prophylaxis (PrEP) in the United States.SettingThirty-five women in a HIV PrEP implementation study attended their week 24 visit at a San Diego research clinic and provided CVF specimens.MethodsWomen in the Adherence Enhancement Guided by Individualized Texting and Drug Levels study had their CVF specimens evaluated for (1) sexually transmitted bacterial (Neisseria gonorrhoeae, Chlamydia trachomatis, Gardnerella, and Trichomonas vaginalis), viral (human papillomavirus, cytomegalovirus and herpes simplex virus-1/2) and fungal (Candida) infections; (2) microbiome composition by 16 S sequencing (V3-V4 region); and (3) cytokine profiles by enzyme-linked immunoassay (Interleukin-8, macrophage Inflammatory protein-1a, macrophage Inflammatory Protein-1b and interferon-γ-inducible protein-10). Univariate statistical analysis was used to determine factors associated with CVF TFV concentrations. CVF TFV of 100-1000 ng/mL benchmarked typical genital concentrations and TFV-diphosphate in dried blood spots of 700 fmol/punch was considered adequate adherence.ResultsThirty-five women had CVF specimens collected. No factor was associated with CVF TFV concentrations or discordance of blood and vaginal concentrations. Among 27 participants assessed for vaginosis (Candida, Gardnerella or Trichomonas), women with Gardnerella (n = 11) were more likely to have high (>1000 ng/mL) CVF TFV concentrations (82% versus 33%, P = 0.02).ConclusionsPresence of genital viruses, cytokines, or vaginal community state types were not associated with low CVF TFV concentrations in cisgender women taking oral tenofovir disoproxil fumarate/emtricitable for PrEP. The surprising association observed between presence of Gardnerella and higher vaginal TFV concentrations needs further evaluation.
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- 2022
19. Antiviral potency of long-acting islatravir subdermal implant in SHIV-infected macaques
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Pons-Faudoa, Fernanda P., Di Trani, Nicola, Capuani, Simone, Facchi, Ilaria, Wood, Anthony M., Nehete, Bharti, DeLise, Ashley, Sharma, Suman, Shelton, Kathryn A., Bushman, Lane R., Chua, Corrine Ying Xuan, Ittmann, Michael M., Kimata, Jason T., Anderson, Peter L., Nehete, Pramod N., Arduino, Roberto C., and Grattoni, Alessandro
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- 2024
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20. Sex Hormone Therapy and Tenofovir Diphosphate Concentration in Dried Blood Spots: Primary Results of the Interactions Between Antiretrovirals And Transgender Hormones Study
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Grant, Robert M, Pellegrini, Marion, Defechereux, Patricia A, Anderson, Peter L, Yu, Michelle, Glidden, David V, O’Neal, Joshua, Yager, Jenna, Bhasin, Shalender, Sevelius, Jae, and Deutsch, Madeline B
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Biomedical and Clinical Sciences ,Clinical Sciences ,Sexual and Gender Minorities (SGM/LGBT*) ,Prevention ,Clinical Research ,Infectious Diseases ,HIV/AIDS ,Adenine ,Anti-HIV Agents ,Emtricitabine ,Estradiol ,Female ,HIV Infections ,Humans ,Male ,Organophosphates ,Pre-Exposure Prophylaxis ,Transgender Persons ,HIV ,preexposure prophylaxis ,transgender ,sex hormones ,pharmacokinetics ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundSex hormone and preexposure prophylaxis (PrEP) drug interactions among transgender women (TGW), transgender men (TGM), and cisgender men (CGM) are not fully understood.MethodsTGM and TGW on at least 6 months of stable sex hormone therapy containing testosterone or estradiol (respectively) were enrolled in a 4-week study of directly observed dosing of daily oral coformulated emtricitabine and tenofovir disoproxil fumarate (FTC/TDF). TFV-DP in dried blood spots and sex hormones in serum were measured at weekly intervals. TFV-DP was compared with 2- and 4-week samples from Directly Observed Therapy Dried Blood Spots (DOT-DBS) Study (NCT02022657).ResultsFrom May 2017 to June 2018, 24 TGM and 24 TGW were enrolled. Testosterone (total and free) and estradiol concentrations were comparable before and after 4 weeks of PrEP use in TGM and TGW, respectively. Historical controls included 17 cisgender women (CGW) and 15 CGM. TFV-DP concentrations at week 4 were comparable between TGW and TGM (mean difference, -6%; 95% confidence interval [CI], -21% to 12%; P = .47), comparable between TGW and CGM (mean difference, -12%; 95% CI, -27% to 7%; P = .21) and were lower among TGM compared with CGW (mean difference, -23%; 95% CI, -36% to -7%; P = .007). All persons in all groups were projected to reach the TFV-DP threshold that has been associated with high protection from human immunodeficiency virus.ConclusionsCGM, TGM, and TGW had comparable TFV-DP concentrations in dried blood spots after 4 weeks of directly observed daily FTC/TDF PrEP use. Serum hormone concentrations were not affected by FTC/TDF PrEP use.Clinical trials registrationNCT04050371.
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- 2021
21. Results from a Pre-exposure Prophylaxis Demonstration Project for At-risk Cisgender Women in the United States
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Blumenthal, Jill, Jain, Sonia, He, Feng, Amico, K Rivet, Kofron, Ryan, Ellorin, Eric, Stockman, Jamila K, Psaros, Christina, Ntim, Gifty M, Chow, Karen, Anderson, Peter L, Haubrich, Richard, Corado, Katya, Moore, David J, Morris, Sheldon, and Landovitz, Raphael J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Prevention ,Pediatric ,Infectious Diseases ,Clinical Research ,Clinical Trials and Supportive Activities ,Pediatric AIDS ,HIV/AIDS ,Behavioral and Social Science ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Adolescent ,Adult ,Anti-HIV Agents ,Emtricitabine ,Female ,HIV Infections ,Humans ,Medication Adherence ,Middle Aged ,Pre-Exposure Prophylaxis ,Tenofovir ,United States ,pre-exposure prophylaxis ,cisgender women ,adherence ,retention ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundDaily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is effective for reducing human immunodeficiency virus (HIV) acquisition among cisgender women. We report results from the first US observational open-label demonstration project of pre-exposure prophylaxis (PrEP) among at-risk cisgender women.MethodsAdherence Enhancement Guided by Individualized Texting and Drug Levels was a 48-week, single-arm, open-label demonstration study of daily oral TDF/FTC in cisgender women ≥18 years old at risk for HIV. Adherence was supported using 2-way text messaging and titrated adherence counseling based on rapid-turnaround tenofovir diphosphate concentrations from dried blood spots. Study visits occurred at baseline, weeks 4 and 12, and quarterly through week 48. Outcomes included TDF/FTC adherence, retention, and persistence.ResultsFrom June 2016 to October 2018, 136 cisgender women enrolled (mean age, 40 years (standard deviation, 11); 38% non-Hispanic Black and 19% Latina). At 48 weeks, 84 (62%) participants were retained and 62 (46%) remained on PrEP. More than one-third (12/31) of those on study but off PrEP throughout the study discontinued TDF/FTC because of side effects, and 1 adverse event led to study discontinuation. Of 120 participants with drug concentrations measured, 67 (56%) had at least 1 concentration consistent with 6 doses/week; 22 (18%) had consistent ≥6 doses/week across all study visits attended. There were no incident HIV infections and 4 incident bacterial sexually transmitted infections.ConclusionAdequate PrEP adherence for protective drug concentrations was not achieved for most study participants. More work needs to be done to fully explicate the reasons for nonadherence and low retention in cisgender women.
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- 2021
22. Randomized Controlled Trial of Automated Directly Observed Therapy for Measurement and Support of PrEP Adherence Among Young Men Who have Sex with Men
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Buchbinder, Susan P., Siegler, Aaron J., Coleman, Kenneth, Vittinghoff, Eric, Wilde, Gretchen, Lockard, Annie, Scott, Hyman, Anderson, Peter L., Laborde, Nicole, van der Straten, Ariane, Christie, Richard H., Marlborough, Michelle, and Liu, Albert Y.
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- 2023
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23. Lower Urine Tenofovir Concentrations Among Individuals Taking Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate: Implications for Point-of-Care Testing.
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Johnson, Kelly A, Niu, Xin, Glidden, David V, Castillo-Mancilla, Jose R, Yager, Jenna, MaWhinney, Samantha, Morrow, Mary, Okochi, Hideaki, Cressey, Tim R, Drain, Paul K, Gandhi, Monica, Anderson, Peter L, and Spinelli, Matthew A
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directly observed therapy ,pharmacokinetics ,point-of-care adherence monitoring ,tenofovir alafenamide ,tenofovir disoproxil fumarate - Abstract
From directly observed therapy studies, urine tenofovir (TFV) levels were 74% lower when taking tenofovir alafenamide (TAF) vs tenofovir disoproxil fumarate. Urine TFV remains quantifiable across a range of TAF adherence patterns, but a separate point-of-care lateral flow immunoassay with a lower TFV threshold will be needed to support TAF adherence monitoring.
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- 2021
24. Use of Drug-level Testing and Single-genome Sequencing to Unravel a Case of Human Immunodeficiency Virus Seroconversion on Pre-exposure Prophylaxis
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Spinelli, Matthew A, Lowery, Brentton, Shuford, Jennifer A, Spindler, Jon, Kearney, Mary F, McFarlane, Jenny R, McDonald, Cheryl, Okochi, Hideaki, Phung, Nhi, Kuncze, Karen, Jee, Kathryn, Johannessen, DeeJay, Anderson, Peter L, Smith, Dawn K, Defechereux, Patricia, Grant, Robert M, and Gandhi, Monica
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Biomedical and Clinical Sciences ,Clinical Sciences ,Human Genome ,Genetics ,2.2 Factors relating to the physical environment ,Infection ,Good Health and Well Being ,Anti-HIV Agents ,Emtricitabine ,HIV ,HIV Infections ,Humans ,Medication Adherence ,Pharmaceutical Preparations ,Pre-Exposure Prophylaxis ,Seroconversion ,Tenofovir ,PrEP ,HIV seroconversion ,adherence ,single-genome-sequencing ,PrEP failure ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
Cases of seroconversion on pre-exposure prophylaxis (PrEP) should be carefully investigated, given their public health implications and rarity. We report a case of transmitted drug resistance causing seroconversion on PrEP in spite of high adherence, confirmed with dried blood spot and segmental hair drug-level testing and single-genome sequencing.
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- 2021
25. Using the adherence‐efficacy relationship of emtricitabine and tenofovir disoproxil fumarate to calculate background HIV incidence: a secondary analysis of a randomized, controlled trial
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Glidden, David V, Das, Moupali, Dunn, David T, Ebrahimi, Ramin, Zhao, Yongwu, Stirrup, Oliver T, Baeten, Jared M, and Anderson, Peter L
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HIV/AIDS ,Sexual and Gender Minorities (SGM/LGBT*) ,Prevention ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Anti-HIV Agents ,Bayes Theorem ,Emtricitabine ,Female ,HIV Infections ,Homosexuality ,Male ,Humans ,Male ,Pre-Exposure Prophylaxis ,Sexual and Gender Minorities ,Tenofovir ,counterfactual ,PrEP ,clinical trial design ,tenofovir alafenamide ,tenofovir disoproxil fumarate ,Bayesian inference ,Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences - Abstract
IntroductionRandomized trials of new agents for HIV pre-exposure prophylaxis (PrEP) compare against emtricitabine and tenofovir disoproxil fumarate (F/TDF), without a placebo group. We used the well-characterized adherence-efficacy relationship for F/TDF to back-calculate the (non-PrEP) counterfactual background HIV incidence (bHIV) in a randomized trial of a novel PrEP agent and estimate comparative efficacy (to counterfactual bHIV).MethodsThe DISCOVER trial (ClinicalTrials.gov: NCT02842086) randomized 5387 men who have sex with men (MSM) and transgender women who have sex with men and demonstrated non-inferiority of emtricitabine and tenofovir alafenamide (F/TAF) to F/TDF (HIV incidence rate ratio [IRR] 0·47, 95% CI: 0·19 to 1.15). Tenofovir diphosphate (TFV-DP) levels in dried blood spots (DBS) were assessed for all diagnosed with HIV and in a random 10% of the cohort. We used a Bayesian model with a diffuse prior distribution, derived from established data relating tenofovir diphosphate levels to HIV prevention efficacy. This prior, combined with the F/TDF seroconversion rate and tenofovir diphosphate levels in DISCOVER, yielded Bayesian inferences on the counterfactual bHIV.ResultsThere were six versus 11 postbaseline HIV infections (0.14 vs. 0.25/100 person-years [PY]) on F/TAF and F/TDF respectively. Of the 11 on F/TDF, 10 had low, none had medium and one had high tenofovir diphosphate levels; among HIV-negative controls, 5% of the person-time years had low, 9% had medium and 86% had high TFV-DP levels. A non-informative prior distribution for counterfactual bHIV, combined with the prior for TFV-DP level-efficacy relationship, yielded a posterior counterfactual bHIV of 3·4 infections/100 PY (0.80 Bayesian credible interval [CrI] 1·9 to 5·9), which suggests a median HIV efficacy of 96% (0.95 CrI [88% to 99%]) for F/TAF and 93% (0.95 CrI [87% to 96%]) for F/TDF compared to bHIV.ConclusionsBased on the established connection of drug concentrations to PrEP prevention efficacy, a Bayesian framework can be used to estimate a synthetic non-PrEP control group in randomized, active-controlled PrEP trials that include a F/TDF-comparator group.
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- 2021
26. Association of tenofovir diphosphate and lamivudine triphosphate concentrations with HIV and HBV viral suppression
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Lartey, Margaret, Ganu, Vincent J., Tachi, Kenneth, Yang, Hongmei, Anderson, Peter L., Langaee, Taimour, Ojewale, Oluwayemisi, Boamah, Isaac, Obo-Akwa, Adjoa, Antwi, Kenneth, Bushman, Lane R., Ellison, Lucas, and Kwara, Awewura
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- 2023
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27. Changes in local tissue microenvironment in response to subcutaneous long-acting delivery of tenofovir alafenamide in rats and non-human primates
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Pons-Faudoa, Fernanda P., Di Trani, Nicola, Capuani, Simone, Hernandez, Nathanael, Wood, Anthony M., Nehete, Bharti, Niles, Jean, Shelton, Kathryn A., Kezar, Sarah, Bushman, Lane R., Chua, Corrine Ying Xuan, Ittmann, Michael M., Anderson, Peter L., Nehete, Pramod N., Arduino, Roberto C., Nichols, Joan E., and Grattoni, Alessandro
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- 2023
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28. Development and validation of an LC-MS/MS method to quantify the alcohol biomarker phosphatidylethanol 16:0/18:1 in dried blood spots for clinical research purposes
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Salah, Lana M., Bushman, Lane R., Brooks, Kristina M., Anderson, Peter L., and Kiser, Jennifer J.
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- 2023
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29. Approaches to Objectively Measure Antiretroviral Medication Adherence and Drive Adherence Interventions
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Spinelli, Matthew A, Haberer, Jessica E, Chai, Peter R, Castillo-Mancilla, Jose, Anderson, Peter L, and Gandhi, Monica
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Research ,Infectious Diseases ,Sexually Transmitted Infections ,Behavioral and Social Science ,Prevention ,HIV/AIDS ,Infection ,Good Health and Well Being ,Adenine ,Adult ,Anti-HIV Agents ,Emtricitabine ,Female ,HIV Infections ,Hair ,Humans ,Leukocytes ,Mononuclear ,Male ,Medication Adherence ,Monitoring ,Ambulatory ,Organophosphates ,Pre-Exposure Prophylaxis ,Tenofovir ,Viral Load ,Adherence metrics ,PrEP ,ART ,Pharmacologic metrics ,Electronic adherence monitors ,Ingestible sensors ,Immunology ,Virology ,Clinical sciences - Abstract
Purpose of reviewTraditional methods to assess antiretroviral adherence, such as self-report, pill counts, and pharmacy refill data, may be inaccurate in determining actual pill-taking to both antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP). HIV viral loads serve as surrogates of adherence on ART, but loss of virologic control may occur well after decreases in adherence and viral loads are not relevant to PrEP.Recent findingsPharmacologic measures of adherence, electronic adherence monitors, and ingestible electronic pills all serve as more objective metrics of adherence, surpassing self-report in predicting outcomes. Pharmacologic metrics can identify either recent adherence or cumulative adherence. Recent dosing measures include antiretroviral levels in plasma or urine, as well as emtricitabine-triphosphate in dried blood spots (DBS) for those on tenofovir-emtricitabine-based therapy. A urine tenofovir test has recently been developed into a point-of-care test for bedside adherence monitoring. Cumulative adherence metrics assess adherence over weeks to months and include measurement of tenofovir-diphosphate in peripheral blood mononuclear cells or DBS, as well as ART levels in hair. Electronic adherence monitors and ingestible electronic pills can track pill bottle openings or medication ingestion, respectively. New and objective approaches in adherence monitoring can be used to detect nonadherence prior to loss of prevention efficacy or virologic control with PrEP or ART, respectively.
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- 2020
30. PrEP initiation, persistence, and adherence during pregnancy through the postpartum period: a prospective analysis in Kenya
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Pintye, Jillian, Kinuthia, John, Abuna, Felix, Anderson, Peter L., Dettinger, Julia C., Gomez, Laurén, Haberer, Jessica E., Marwa, Mary, Mwongeli, Nancy, Omondi, Pascal., Ochieng, Ben, Stern, Joshua, Watoyi, Salphine, Baeten, Jared M., and John-Stewart, Grace
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- 2023
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31. HIV pre-exposure prophylaxis initiation, persistence, and adherence during pregnancy through the postpartum period
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Pintye, Jillian, Kinuthia, John, Abuna, Felix, Anderson, Peter L., Dettinger, Julia C., Gomez, Laurén, Haberer, Jessica E., Marwa, Mary M., Ngumbau, Nancy, Omondi, Pascal, Odhiambo, Ben, Stern, Joshua, Watoyi, Salphine, Baeten, Jared M., and John-Stewart, Grace
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- 2023
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32. Establishing adherence–concentration–efficacy thresholds of TDF–FTC pre-exposure prophylaxis for HIV prevention in African women: a protocol for the Women TDF–FTC Benchmark Study
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Wu, Linxuan, primary, Saina, Matilda, additional, Brown, Clare, additional, Chege, David, additional, Donnell, Deborah, additional, Glidden, David V., additional, Ngure, Kenneth, additional, Mugo, Nelly R., additional, Akelo, Nina, additional, Schaafsma, Torin, additional, Anderson, Peter L., additional, and Mugwanya, Kenneth K., additional
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- 2024
- Full Text
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33. Miniature mass spectrometer–based point-of-care assay for cabotegravir and rilpivirine in whole blood
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Pandey, Sangeeta, Hu, Yanyang, Bushman, Lane R., Castillo-Mancilla, Jose, Anderson, Peter L., and Cooks, R. Graham
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- 2022
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34. Effective use of pre-exposure prophylaxis (PrEP) Among stimulant users with multiple condomless sex partners: a longitudinal study of men who have sex with men in Los Angeles
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Goodman-Meza, David, Beymer, Matthew R, Kofron, Ryan M, Amico, K Rivet, Psaros, Christina, Bushman, Lane R, Anderson, Peter L, Bolan, Robert, Jordan, Wilbert C, Rooney, James F, Wohl, Amy R, and Landovitz, Raphael J
- Subjects
Public Health ,Health Sciences ,Sexual and Gender Minorities (SGM/LGBT*) ,Prevention ,HIV/AIDS ,Clinical Research ,Adenine ,Adult ,Anti-Retroviral Agents ,Central Nervous System Stimulants ,Condoms ,HIV Infections ,Homosexuality ,Male ,Humans ,Longitudinal Studies ,Los Angeles ,Male ,Medication Adherence ,Organophosphates ,Pre-Exposure Prophylaxis ,Sexual Partners ,Tenofovir ,Unsafe Sex ,PrEP ,adherence ,MSM ,stimulant ,condomless anal sex ,Public Health and Health Services ,Psychology ,Public health ,Sociology ,Clinical and health psychology - Abstract
PrEP's potential benefit for men who have sex with men (MSM) who use stimulants may be limited by adherence or prescriber willingness to recommend PrEP due to concerns of non-compliance. Using data from PATH-PrEP, a 48-week study evaluating PrEP for MSM in Los Angeles, we modeled an interaction between stimulant use and condomless sex with multiple partners (CAS-MP) on prevention-effective dried blood spot tenofovir-diphosphate concentrations. At week 4, participants reporting stimulant use and CAS-MP had a decreased odds of prevention-effective adherence compared to non-stimulant use and non-CAS-MP (AOR 0.15, 95% CI 0.04-0.57). From week 4-48, participants reporting stimulant use and CAS-MP had increased odds of prevention-effective adherence (AOR 1.06 per week, 95%CI 1.01-1.12). Participants reporting CAS-MP without stimulant use had no significant change in prevention-effective adherence (AOR 0.99 per week, 95%CI 0.96-1.02). Stimulant use moderated the association of CAS-MP on prevention-effective PrEP adherence over time.
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- 2019
35. Impact of Estimated Pre-Exposure Prophylaxis (PrEP) Adherence Patterns on Bone Mineral Density in a Large PrEP Demonstration Project
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Spinelli, Matthew A, Glidden, David V, Anderson, Peter L, Gandhi, Monica, McMahan, Vanessa M, Defechereux, Patricia, Schechter, Mauro, Veloso, Valdiléa G, Chariyalertsak, Suwat, Guanira, Juan V, Bekker, Linda-Gail, Buchbinder, Susan P, and Grant, Robert M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Sexual and Gender Minorities (SGM/LGBT*) ,Health Disparities ,Prevention ,Clinical Research ,Behavioral and Social Science ,Musculoskeletal ,Absorptiometry ,Photon ,Adult ,Anti-HIV Agents ,Bone Density ,Cohort Studies ,Dried Blood Spot Testing ,Female ,HIV Infections ,Hip ,Homosexuality ,Male ,Humans ,Male ,Medication Adherence ,Pre-Exposure Prophylaxis ,Spine ,Tenofovir ,Transgender Persons ,Young Adult ,PrEP ,adherence ,men who have sex with men ,transgender people ,bone mineral density ,cohort studies ,Virology ,Clinical sciences - Abstract
Bone mineral density (BMD) declines due to tenofovir-containing pre-exposure prophylaxis (PrEP) have varied among PrEP demonstration projects, potentially related to variable adherence. Characterization of BMD changes in highly adherent individuals, estimated via tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS), can assist clinicians when counseling patients. Cisgender men who have sex with men and transwomen in the optional dual-energy X-ray absorptiometry (DXA) substudy of a large, international, open-label PrEP demonstration project, the iPrEx-open-label extension (OLE) study underwent DXA scans and DBS collection every 24 weeks, with average weekly dosing adherence patterns (2, 4, and 7 doses/week) estimated from validated TFV-DP cut-offs. The mean percent BMD change was estimated in strata of average weekly adherence by using a linear mixed-effects model to calculate the BMD decline in highly adherent individuals on PrEP for the first time. DXA/DBS data were available for 254 individuals over a median of 24 weeks in iPrEx-OLE from June 2011 to December 2013. The percent decline in spine BMD was monotonically associated with strata of increasing average weekly adherence (p
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- 2019
36. Brief Report: Short-Term Adherence Marker to PrEP Predicts Future Nonretention in a Large PrEP Demo Project: Implications for Point-of-Care Adherence Testing.
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Spinelli, Matthew A, Glidden, David V, Anderson, Peter L, Gandhi, Monica, Cohen, Stephanie, Vittinghoff, Eric, Coleman, Megan E, Scott, Hyman, Bacon, Oliver, Elion, Richard, Kolber, Michael A, Buchbinder, Susan P, and Liu, Albert Y
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Public Health ,Health Sciences ,Behavioral and Social Science ,Infectious Diseases ,Sexually Transmitted Infections ,Adenine ,Adult ,Anti-HIV Agents ,Dried Blood Spot Testing ,Emtricitabine ,Female ,HIV Infections ,Homosexuality ,Male ,Humans ,Male ,Medication Adherence ,Organophosphates ,Point-of-Care Testing ,Pre-Exposure Prophylaxis ,Proportional Hazards Models ,Prospective Studies ,Tenofovir ,PrEP ,adherence ,retention in care ,persistence ,dried blood spot ,Clinical Sciences ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BACKGROUND:Objective adherence metrics for tenofovir (TFV) disoproxil fumarate/emtricitabine(FTC)-based PrEP were critical for interpretation of efficacy in PrEP clinical trials, and there is increasing interest in using drug levels to tailor interventions for reengagement and adherence. Point-of-care immunoassays (POC) for TFV, which examine short-term adherence, are in development. However the ability of poor short-term and long-term adherence to predict future PrEP non-retention is unknown. SETTING:Secondary data analysis of a large, prospective multi-site U.S. PrEP demonstration project METHODS:: An adjusted Cox-proportional hazards model examined the relationship of dried blood spot (DBS) levels of FTC-triphosphate (FTC-TP) or TFV-diphosphate (TFV-DP), measures of short-term and long-term PrEP adherence, respectively, with future study non-retention. RESULTS:Overall, 294 individuals (median age 33 years) contributed drug levels within the U.S. PrEP demonstration project. By study end, 27% were lost to follow-up, 25% had at least one undetectable FTC-TP level indicating poor short-term adherence, and 29% had a drug level indicating sub-optimal long-term adherence (TFV-DP
- Published
- 2019
37. Predictors of Long-Term HIV Pre-exposure Prophylaxis Adherence After Study Participation in Men Who Have Sex With Men.
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Hoenigl, Martin, Hassan, Adiba, Moore, David J, Anderson, Peter L, Corado, Katya, Dubé, Michael P, Ellorin, Eric E, Blumenthal, Jill, and Morris, Sheldon R
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Behavioral and Social Science ,HIV/AIDS ,Clinical Research ,Prevention ,Good Health and Well Being ,Adenine ,Adult ,Follow-Up Studies ,HIV Infections ,Homosexuality ,Male ,Humans ,Logistic Models ,Male ,Medication Adherence ,Middle Aged ,Organophosphates ,Pre-Exposure Prophylaxis ,Regression Analysis ,Risk-Taking ,Sexual and Gender Minorities ,adherence ,continuum ,real-life cohort ,substance use ,risk behavior ,California Collaborative Treatment Group (CCTG) 601 Team ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundEfficacy of HIV pre-exposure prophylaxis (PrEP) among men who have sex with men is well documented in randomized trials. After trial completion, participants are challenged with acquiring PrEP on their own and remaining adherent.MethodsThis was a follow-up study of the TAPIR randomized controlled multicenter PrEP trial. Participants were contacted after their last TAPIR visit (ie, after study-provided PrEP was discontinued) to attend observational posttrial visits 24 and 48 weeks later. Adherence during TAPIR and posttrial visits was estimated by dried blood spot intracellular tenofovir diphosphate levels (adequate adherence defined as tenofovir diphosphate levels >719 fmol/punch). Binary logistic regression analysis assessed predictors of completing posttrial visits and PrEP adherence among participants completing ≥1 visit.ResultsOf 395 TAPIR participants who were on PrEP as part of the TAPIR trial for a median of 597 days (range 3-757 days), 122 (31%) completed ≥1 posttrial visit (57% of University of California San Diego participants completed posttrial visits, whereas this was 13% or lower for other study sites). Among participants who completed ≥1 posttrial visit, 57% had adequate adherence posttrial. Significant predictors of adequate adherence posttrial were less problematic substance use, higher risk behavior, and adequate adherence in year 1 of TAPIR.ConclusionMore than half of PrEP users followed after trial completion had successfully acquired PrEP and showed adequate adherence. Additional adherence monitoring and intervention measures may be needed for those with low PrEP adherence and problematic substance use during the first year of trial.
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- 2019
38. Self-initiated continuation of and adherence to HIV pre-exposure prophylaxis (PrEP) after PrEP demonstration project roll-off in men who have sex with men: associations with risky decision making, impulsivity/disinhibition, and sensation seeking
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Hoenigl, Martin, Morgan, Erin, Franklin, Donald, Anderson, Peter L, Pasipanodya, Elizabeth, Dawson, Matthew, Hanashiro, Marvin, Ellorin, Eric E, Blumenthal, Jill, Heaton, Robert, Moore, David J, and Morris, Sheldon R
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Medical Microbiology ,Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Mental Health ,Sexual and Gender Minorities (SGM/LGBT*) ,Behavioral and Social Science ,HIV/AIDS ,Infectious Diseases ,Clinical Research ,Prevention ,Aetiology ,2.3 Psychological ,social and economic factors ,Mental health ,Good Health and Well Being ,Adult ,Aged ,Anti-HIV Agents ,Decision Making ,HIV Infections ,Homosexuality ,Male ,Humans ,Impulsive Behavior ,Male ,Medication Adherence ,Middle Aged ,Pre-Exposure Prophylaxis ,Risk-Taking ,Sexual and Gender Minorities ,Tenofovir ,Sensation seeking ,Stimulant substance use ,Seroconversion ,Dried blood spot ,Adherence ,California Collaborative Treatment Group (CCTG) 601 Team ,Virology ,Clinical sciences ,Medical microbiology - Abstract
The objective of this study was to examine differences in the levels of risky decision making and other frontal system behavior constructs in relation to self-initiated continuance of HIV pre-exposure prophylaxis (PrEP) and PrEP adherence outcomes among men who have sex with men (MSM) following completion of a clinical PrEP trial. At the last PrEP trial visit, study provided PrEP was discontinued and participants were navigated to the community for PrEP continuation. In this cross-sectional analysis, 84/187 (45%) MSM who completed a prospective observational post-PrEP trial follow-up visit at the University of California San Diego were included. PrEP adherence was measured using dried blood spot tenofovir diphosphate (TFV-DP) levels. Risky decision making was assessed using the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), while impulsivity/disinhibition, sensation seeking, and substance use were assessed via standardized self-report questionnaires. A total of 58/84 (69%) of MSM who completed the 12-month post-study visit continued PrEP. Of those, n = 46 (79%) reached TFV-DP levels associated with adequate adherence. Individuals who elected to continue PrEP 12 months post-trial had riskier decision making on BART, but less impulsivity/disinhibition compared to individuals who did not continue PrEP. Neither risky decision making nor impulsivity/disinhibition/sensation seeking nor substance use correlated with PrEP adherence. Our findings suggest that those with risky decision making may have greater insight into their HIV risks, and therefore be more likely to continue to use PrEP. However, elevated impulsivity/disinhibition, indicative of greater neurobehavioral alterations, was negatively associated with PrEP continuance and is a potential target for future interventions to help people link to PrEP.
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- 2019
39. The pharmacokinetics, pharmacodynamics, and mucosal responses to maraviroc-containing pre-exposure prophylaxis regimens in MSM
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McGowan, Ian, Wilkin, Timothy, Landovitz, Raphael J, Wu, Chunyuan, Chen, Ying, Marzinke, Mark A, Hendrix, Craig W, Richardson, Paul, Eshleman, Susan H, Andrade, Adriana, Chege, Wairimu, Anderson, Peter L, McCauley, Marybeth, Farley, Jason, Mayer, Kenneth H, Anton, Peter, Brand, Rhonda M, Cranston, Ross D, and Gulick, Roy
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,HIV/AIDS ,Prevention ,Clinical Research ,Sexual and Gender Minorities (SGM/LGBT*) ,Clinical Trials and Supportive Activities ,Infection ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Anti-HIV Agents ,Blood Chemical Analysis ,Double-Blind Method ,Drug Therapy ,Combination ,HIV Infections ,Homosexuality ,Male ,Humans ,Intestinal Mucosa ,Lymphoid Tissue ,Male ,Maraviroc ,Middle Aged ,Pre-Exposure Prophylaxis ,Prospective Studies ,Rectum ,Young Adult ,explant challenge ,HIV ,maraviroc ,MSM ,pharmacodynamic ,pharmacokinetic ,clinical trial ,pre-exposure prophylaxis ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectiveHIV Prevention Trials Network 069/AIDS Clinical Trials Group A5305 was a study of 48-week oral pre-exposure prophylaxis (PrEP) regimens in MSM and transgender women. A rectal substudy was included to evaluate drug concentrations in rectal compartment vs. blood, gut-associated lymphoid tissue (GALT) responses to four antiretroviral PrEP regimens [maraviroc (MVC), MVC + emtricitabine (FTC), MVC + tenofovir (TFV) disoproxil fumarate, and TFV disoproxil fumarate + FTC], and to determine whether ARV exposure was associated with ex-vivo suppression of HIV infection in colorectal explants.MethodsC-C chemokine receptor type 5 (CCR5) genotype was characterized using PCR. At baseline and at Weeks 24, 48, and 49, GALT phenotype was characterized by flow cytometry, rectal biopsies were challenged with HIV-1BaL, and tissue and plasma pharmacokinetics were measured via mass spectrometry.ResultsExposure to MVC was not associated with increased expression of CD4+/CCR5+ HIV target T cells. Significant ex-vivo viral suppression compared with baseline was seen at Weeks 24 and 48, ranging from 1.4 to 1.8 log10 for all study regimens except the MVC-alone arm which did not show statistically significant viral suppression at Week 48. Tissue concentrations of TFV, TFV-diphosphate, and FTC were correlated with viral suppression.ConclusionMVC-containing HIV PrEP regimens did not increase GALT CD4+ T-cell activation or the CD4+/CCR5+ phenotype. No virologic suppression was seen with MVC-alone at Week 48 compared with combination regimens, suggesting MVC monotherapy might be less effective than combination antiretroviral PrEP regimens.
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- 2019
40. Short Communication: Association of Vitamin D Insufficiency and Protective Tenofovir Diphosphate Concentrations with Bone Toxicity in Adolescent Boys and Young Men Using Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Pre-Exposure Prophylaxis
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Havens, Peter L, Tamhane, Ashutosh, Stephensen, Charles B, Schuster, Gertrud U, Gordon, Catherine M, Liu, Nancy, Wilson, Craig M, Hosek, Sybil G, Anderson, Peter L, Kapogiannis, Bill G, and Mulligan, Kathleen
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,HIV/AIDS ,Clinical Trials and Supportive Activities ,Prevention ,Adolescent ,Anti-HIV Agents ,Bone and Bones ,Emtricitabine ,HIV Infections ,Homosexuality ,Male ,Humans ,Logistic Models ,Male ,Pre-Exposure Prophylaxis ,Prospective Studies ,Tenofovir ,Vitamin D ,Vitamin D Deficiency ,Young Adult ,tenofovir disoproxil fumarate ,bone mineral density ,HIV pre-exposure prophylaxis ,25-hydroxy vitamin D ,Virology ,Clinical sciences - Abstract
We examined associations of 25-hydroxy vitamin D (25-OHD), tenofovir disoproxil fumarate (TDF), and bone toxicity. We studied TDF/emtricitabine (FTC) HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Bone toxicity was predefined using bone mineral density/content change from baseline to week 48. Baseline serum 25-OHD was dichotomized as 700 fmol/punch (protective against HIV acquisition) versus ≤700. Associations were examined by univariate and multivariable logistic regression, reporting crude and adjusted odds ratios (ORs), with 95% confidence intervals (CIs). Of 101 enrolled, 69 had complete bone assessments and 25-OHD; of these, 59 had week 48 TFV-DP data. Median (Q1-Q3) age was 20 (18-21) years; 54% were black/African American. In univariate analysis, participants with baseline 25-OHD 700 (OR = 11.5; 95% CI = 1.4-169.6), 25-OHD 700 (OR = 32.3; 95% CI = 3.3-653.6) had greater odds of bone toxicity after adjusting for race. In multivariable models, 25-OHD insufficiency, protective TFV-DP concentrations, and black race were significantly associated with bone toxicity after 48 weeks of TDF/FTC PrEP in YMSM. Clinical Trials Registration: NCT01769469.
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- 2019
41. Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report
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Cohen, Stephanie E, Sachdev, Darpun, Lee, Sulggi A, Scheer, Susan, Bacon, Oliver, Chen, Miao-Jung, Okochi, Hideaki, Anderson, Peter L, Kearney, Mary F, Coffey, Susa, Scott, Hyman, Grant, Robert M, Havlir, Diane, and Gandhi, Monica
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Prevention ,Sexually Transmitted Infections ,Infectious Diseases ,HIV/AIDS ,Infection ,Good Health and Well Being ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundPre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly protective against HIV infection. We report a case of tenofovir-susceptible, emtricitabine-resistant HIV acquisition despite high adherence to daily PrEP.MethodsAdherence to PrEP was assessed by measuring concentrations of emtricitabine and tenofovir disoproxil fumarate or their metabolites in plasma, dried blood spots, and hair. After seroconversion, genotypic and phenotypic resistance of the acquired virus was determined by standard clinical tests and by single-genome sequencing of proviral genomes. HIV partner services identified the likely transmission partner.FindingsA 21-year-old Latino man tested positive for HIV infection 13 months after PrEP initiation. He had a negative HIV antibody test, but detectable HIV RNA with 559 copies per mL. He reported good adherence to daily PrEP. He was linked to care and immediately started antiretroviral therapy, at which point his RNA was 1544 copies per mL and his HIV antibody test was positive. The HIV genotype revealed Met184Val, Leu74Val, Leu100Ile, and Lys103Asn mutations in reverse transcriptase, and the phenotype showed susceptibility to tenofovir disoproxil fumarate and resistance to emtricitabine. Segmental hair analysis of tenofovir disoproxil fumarate concentrations measured in 1 cm segments of hair from the scalp indicated consistently high adherence to PrEP in each of the 6 months before HIV diagnosis (0·0672-0·0889 ng/mg). Concentrations of tenofovir diphosphate (1012 fmol per punch) and emtricitabine triphosphate (0·266 fmol per punch) in a dried blood spot indicated high adherence over the preceding 6 weeks. Concentrations of emtricitabine (870·5 ng/mL) and tenofovir disoproxil fumarate (188·2 ng/mL) measured in plasma 3 months before HIV seroconversion confirmed adherence in the days preceding that visit. The likely transmission partner was not engaged in HIV primary care and had a similar viral genotype.InterpretationAcquisition of HIV virus that is susceptible to tenofovir disoproxil fumarate, but resistant to emtricitabine can occur despite high adherence to PrEP. Quarterly screening for HIV and sexually transmitted diseases facilitates early diagnosis in people on PrEP; when combined with prompt linkage to care and partner services this can prevent onward transmission of HIV.FundingUS National Institutes of Health.
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- 2019
42. The pharmacokinetics, pharmacodynamics, and mucosal responses to maraviroc-containing PrEP Regimens in Men who have Sex with Men.
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McGowan, Ian, Wilkin, Timothy, Landovitz, Raphael J, Wu, Chunyuan, Chen, Ying, Marzinke, Mark A, Hendrix, Craig W, Richardson, Paul, Eshleman, Susan H, Andrade, Adriana, Chege, Wairimu, Anderson, Peter L, McCauley, Marybeth, Farley, Jason, Mayer, Kenneth H, Anton, Peter, Brand, Rhonda M, Cranston, Ross D, and Gulick, Roy
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Virology ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences - Abstract
OBJECTIVE:HIV Prevention Trials Network 069/AIDS Clinical Trials Group A5305 was a study of 48-week oral pre-exposure prophylaxis (PrEP) regimens in MSM and transgender women. A rectal substudy was included to evaluate drug concentrations in rectal compartment vs. blood, gut-associated lymphoid tissue (GALT) responses to four antiretroviral PrEP regimens [maraviroc (MVC), MVC + emtricitabine (FTC), MVC + tenofovir (TFV) disoproxil fumarate, and TFV disoproxil fumarate + FTC], and to determine whether ARV exposure was associated with ex-vivo suppression of HIV infection in colorectal explants. METHODS:C-C chemokine receptor type 5 (CCR5) genotype was characterized using PCR. At baseline and at Weeks 24, 48, and 49, GALT phenotype was characterized by flow cytometry, rectal biopsies were challenged with HIV-1BaL, and tissue and plasma pharmacokinetics were measured via mass spectrometry. RESULTS:Exposure to MVC was not associated with increased expression of CD4/CCR5 HIV target T cells. Significant ex-vivo viral suppression compared with baseline was seen at Weeks 24 and 48, ranging from 1.4 to 1.8 log10 for all study regimens except the MVC-alone arm which did not show statistically significant viral suppression at Week 48. Tissue concentrations of TFV, TFV-diphosphate, and FTC were correlated with viral suppression. CONCLUSION:MVC-containing HIV PrEP regimens did not increase GALT CD4 T-cell activation or the CD4/CCR5 phenotype. No virologic suppression was seen with MVC-alone at Week 48 compared with combination regimens, suggesting MVC monotherapy might be less effective than combination antiretroviral PrEP regimens.
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- 2018
43. Substance Use and Adherence to HIV Preexposure Prophylaxis for Men Who Have Sex with Men1
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Hoenigl, Martin, Jain, Sonia, Moore, David, Collins, Deborah, Sun, Xiaoying, Anderson, Peter L, Corado, Katya, Blumenthal, Jill S, Daar, Eric S, Milam, Joel, Dubé, Michael P, and Morris, Sheldon
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Public Health ,Biomedical and Clinical Sciences ,Clinical Sciences ,Health Sciences ,Infectious Diseases ,Substance Misuse ,Sexual and Gender Minorities (SGM/LGBT*) ,Drug Abuse (NIDA only) ,Sexually Transmitted Infections ,Clinical Research ,Behavioral and Social Science ,HIV/AIDS ,Prevention ,Good Health and Well Being ,Alcohol Drinking ,California ,Female ,HIV Infections ,Homosexuality ,Male ,Humans ,Male ,Pre-Exposure Prophylaxis ,Proportional Hazards Models ,Public Health Surveillance ,Randomized Controlled Trials as Topic ,Sexual and Gender Minorities ,Sexually Transmitted Diseases ,Substance-Related Disorders ,California Collaborative Treatment Group 595 Team ,HIV ,HIV and other retroviruses ,MSM ,PrEP ,adherence ,adherence to HIV preexposure prophylaxis ,alcohol ,dried blood spots ,injection drug use ,men who have sex with men ,methamphetamine ,persons who injected drugs ,sexually transmitted infections ,substance use ,transgender women ,viruses ,Medical Microbiology ,Public Health and Health Services ,Microbiology ,Clinical sciences ,Epidemiology ,Health services and systems - Abstract
The effectiveness of oral HIV preexposure prophylaxis (PrEP) strongly depends on maintaining adherence. We investigated the association between substance use and PrEP adherence, as well as incident sexually transmitted infections (STIs) in a high-risk cohort of 394 participants (391 men who have sex with men and 3 transgender women) who were enrolled in a PrEP demonstration project. We assessed baseline and ongoing substance use over a 48-week period for stimulants and nonstimulant substances and for each substance separately. We measured PrEP adherence by using dried blood spots to obtain levels of tenofovir diphosphate. No differences in these levels were found between substance users and nonsubstance users. Baseline stimulant use was strongly associated (odds ratio 3.4; p
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- 2018
44. Alignment of PrEP adherence with periods of HIV risk among adolescent girls and young women in South Africa and Zimbabwe: a secondary analysis of the HPTN 082 randomised controlled trial
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Velloza, Jennifer, Donnell, Deborah, Hosek, Sybil, Anderson, Peter L, Chirenje, Z Mike, Mgodi, Nyaradzo, Bekker, Linda-Gail, Marzinke, Mark A, Delany-Moretlwe, Sinead, and Celum, Connie
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- 2022
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45. Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial
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Asmelash, Aida, Sehurutshi, Alice, Baguma, Allan, Marais, Anita, Kawoozo, Barbarah, Malinga, Bongiwe Prudence, Mirembe, Brenda Gati, Okech, Brenda, Esterhuizen, Bryan, Murombedzi, Caroline, Gadama, Daphne, Hwengwere, Eldinah, Roos, Elizabeth, Magada, Elizabeth S, Shava, Emily, Piwowar-Manning, Estelle, Tahuringana, Eunice, Muhlanga, Felix GS, Conradie, Francesca, Angira, Frank, Nanyonjo, Gertrude, Kistnasami, Girisha, Mvula, Hazzie, Naidoo, Ishana, Horak, Jaco, Jere, Jane, Moodley, Jeeva, Shin, Katie, Nel, Kerry, Bokoch, Kevin, Birungi, Lilian, Emel, Lynda, Monametsi, Maletsatsi, Sibanda, Marvelous, Mutambanengwe, Mercy, Chitukuta, Miria, Matimbira, Moleen, Bhondai-Mhuri, Muchaneta, Sibisi, Ncamsile, Morar, Neetha, Mudzonga, Netsai, Natureeba, Paul, Richardson, Paul, Musara, Petina, Macdonald, Pippa, Nkambule, Rejoice, Mosime, Repelang, White, Rhonda, Berhanu, Ribka, Ncube-Sihlongonyane, Ritha, Sekabira, Rogers, Siva, Samantha, Pillay, Saresha, Govender, Shamelle, Bamweyana, Sheiala, Nzimande, Siyabonga, Innes, Steve, Dadabhai, Sufia, Samandari, Taraz, Tembo, Tchangani, Lungu Mabedi, Thandie, Chirenda, Thandiwe, Chidemo, Tinashe, Mudhune, Victor, Naidoo, Vikesh, Samaneka, Wadzanai, Agyei, Yaw, Musodza, Yeukai, Fourie, Yolandie, Gaffoor, Zakir, Delany-Moretlwe, Sinead, Hughes, James P, Bock, Peter, Ouma, Samuel Gurrion, Hunidzarira, Portia, Kalonji, Dishiki, Kayange, Noel, Makhema, Joseph, Mandima, Patricia, Mathew, Carrie, Spooner, Elizabeth, Mpendo, Juliet, Mukwekwerere, Pamela, Mgodi, Nyaradzo, Ntege, Patricia Nahirya, Nair, Gonasagrie, Nakabiito, Clemensia, Nuwagaba-Biribonwoha, Harriet, Panchia, Ravindre, Singh, Nishanta, Siziba, Bekezela, Farrior, Jennifer, Rose, Scott, Anderson, Peter L, Eshleman, Susan H, Marzinke, Mark A, Hendrix, Craig W, Beigel-Orme, Stephanie, Hosek, Sybil, Tolley, Elizabeth, Sista, Nirupama, Adeyeye, Adeola, Rooney, James F, Rinehart, Alex, Spreen, William R, Smith, Kimberly, Hanscom, Brett, Cohen, Myron S, and Hosseinipour, Mina C
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- 2022
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46. Cumulative Tenofovir Exposure Among Patients With HIV/Hepatitis B Coinfection With Differential Viral Suppression.
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Zhang, Helen L, Mock, Meredith, Bushman, Lane, Anderson, Peter L, Kiser, Jennifer J, and Naggie, Susanna
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PATIENT compliance ,ANTIRETROVIRAL agents ,VIRAL load ,RESEARCH funding ,TENOFOVIR ,PILOT projects ,HIV infections ,DESCRIPTIVE statistics ,HEPATITIS B ,VIREMIA ,CASE-control method ,DRUGS ,ANTI-HIV agents ,COMPARATIVE studies ,MIXED infections - Abstract
This case-control study explored cumulative tenofovir exposure among patients with human immunodeficiency virus/hepatis B virus (HIV/HBV) coinfection with HIV viral suppression. Among patients taking tenofovir disoproxil fumarate, median TFV-DP levels in dried blood spots were ∼3-fold lower among patients with incomplete HBV viral suppression (n = 4) compared to those with complete suppression (n = 5) (516 vs 1456 fmol/punch). [ABSTRACT FROM AUTHOR]
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- 2024
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47. A Phase 1 Clinical Trial to Assess the Safety and Pharmacokinetics of a Tenofovir Alafenamide/Elvitegravir Insert Administered Rectally for HIV Prevention.
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Riddler, Sharon A, Kelly, Clifton W, Hoesley, Craig J, Ho, Ken S, Piper, Jeanna M, Edick, Stacey, Heard, Faye, Doncel, Gustavo F, Johnson, Sherri, Anderson, Peter L, Brand, Rhonda M, Ayudhya, Ratiya Pamela Kunjara Na, Bauermeister, José A, Hillier, Sharon L, and Hendrix, Craig W
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CLINICAL trial registries ,RECTAL administration ,HIV infections ,HIV ,HIV prevention ,EMTRICITABINE - Abstract
Background On-demand topical products could be an important tool for human immunodeficiency virus (HIV) prevention. We evaluated the safety, pharmacokinetics, and ex vivo pharmacodynamics of a tenofovir alafenamide/elvitegravir (TAF/EVG, 20 mg/16 mg) insert administered rectally. Methods MTN-039 was a phase 1, open-label, single-arm, 2-dose study. Blood, rectal fluid, and rectal tissue were collected over 72 hours following rectal administration of 1 and 2 TAF/EVG inserts for each participant. Results TAF/EVG inserts were safe and well tolerated. EVG and tenofovir (TFV) were detected in blood plasma at low concentrations: median peak concentrations after 2 inserts were EVG 2.4 ng/mL and TFV 4.4 ng/mL. Rectal tissue EVG peaked at 2 hours (median, 2 inserts = 9 ng/mg) but declined to below limit of quantification in the majority of samples at 24 hours, whereas tenofovir diphosphate (TFV-DP) remained high >2000 fmol/million cells for 72 hours with 2 inserts. Compared to baseline, median cumulative log
10 HIV p24 antigen of ex vivo rectal tissue HIV infection was reduced at each time point for both 1 and 2 inserts (P <.065 and P <.039, respectively). Discussion Rectal administration of TAF/EVG inserts achieved high rectal tissue concentrations of EVG and TFV-DP with low systemic drug exposure and demonstrable ex vivo inhibition of HIV infection for 72 hours. Clinical Trials Registration. NCT04047420. [ABSTRACT FROM AUTHOR]- Published
- 2024
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48. Drug Concentrations in Hair and Dried Blood Spots as Preexposure Prophylaxis Adherence Metrics During Pregnancy and Postpartum.
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Wu, Linxuan, Kinuthia, John, Anderson, Peter L, Baeten, Jared M, Dettinger, Julia C, Gandhi, Monica, Gomez, Laurén, John-Stewart, Grace, Marwa, Mary M, Ngumbau, Nancy, Otieno, Felix, Omondi, Pascal, Odhiambo, Ben, Watoyi, Salphine, and Pintye, Jillian
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HAIR ,HIV ,TENOFOVIR ,PUERPERIUM ,PREGNANCY - Abstract
We evaluated hair tenofovir (TFV) concentrations as an adherence metric for HIV preexposure prophylaxis during pregnancy and postpartum and compared hair levels with TFV-diphosphate levels in dried blood spots (DBSs). Overall 152 hair samples from 102 women and 36 hair-DBS paired samples from 29 women were collected from a subset of women in a cluster-randomized trial. Having a partner with HIV was associated with higher hair TFV levels (P <.001). Hair TFV concentrations were strongly correlated with DBS TFV-diphosphate levels (r = 0.76, P <.001), indicating hair as a promising cumulative adherence metric for perinatal preexposure prophylaxis assessment. [ABSTRACT FROM AUTHOR]
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- 2024
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49. Tenofovir diphosphate levels in dried blood spots are associated with virologic failure and resistance to first-line therapy in South Africa: a case-control cohort study
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Castillo-Mancilla, Jose R., Edwards, Johnathan A., Brijkumar, Jaysingh, Moosa, Mahomed-Yunus, Zhao, Yuan, Ofotokun, Igho, Johnson, Brent A., Lee, Mitchell H., Pillay, Selvan, Pillay, Melendhran, Moodley, Pravi, Kuritzkes, Daniel R., Sunpath, Henry, Bushman, Lane R., Ellison, Lucas, Anderson, Peter L., and Marconi, Vincent C.
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Drug resistance -- Risk factors ,Viremia -- Risk factors ,Tenofovir -- Patient outcomes ,HIV infection -- Drug therapy -- Prognosis ,Health - Abstract
Introduction: Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), a measure of cumulative antiretroviral therapy (ART) adherence, is associated with viral suppression and predicts future viremia in persons with HIV (PWH). However, its utility to identify those at risk for virologic failure (VF) and drug resistance is unknown. To address this, we aimed to establish the association between this adherence biomarker and VF with drug resistance in a cohort of PWH initiating first-line ART in KwaZulu-Natal, South Africa. Methods: PWH initiating TFV disoproxil fumarate (TDF)-based ART within a parent prospective cohort were evaluated. Using a nested design, DBS for TFV-DP were collected from cases who developed VF (HIV-1 RNA [greater than or equal to]1000 copies/ml) after [greater than or equal to]5 months on ART versus controls, matched 1:2 by site, age, gender, race and ART duration. Cases were categorized as having VF with or without resistance using genotyping. One-way analysis of variance (ANOVA) was used to compare TFV-DP for controls, cases with VF and resistance, and cases with VF without resistance. Data are presented as mean (standard deviation, SD) or geometric mean [95% confidence interval, 95% CI]. Results and discussion: One thousand participants were enrolled in the parent study between 2014 and 2016, of which 288 (29%) had DBS available. Of these, 94 (33%) were cases and 194 (67%) were controls; 59% were women. Mean age of our population was 33 (SD 8) years. Genotyping was available in 50 (53%) of the 94 cases. Geometric mean TFV-DP in DBS from controls was 708 [95% CI; 647-773] fmol/punch, which was higher compared to participants having VF with resistance (n = 36), 386 [95% CI; 241-617] fmol/punch and VF without resistance (n = 14), 61 [95% CI; 22-164] fmol/punch; p Conclusions: TFV-DP in DBS showed a stepwise association with VF and drug resistance in South African PWH. Participants having VF with resistance had mid-range concentrations of TFV-DP, which were higher than those for PWH without resistance. Future research on the clinical utility of TFV-DP concentrations in DBS to predict and prevent the development of VF and drug resistance is needed. Keywords: adherence; dried blood spots; HIV resistance; South Africa; tenofovir diphosphate; viral failure, 1 | INTRODUCTION Although current antiretroviral therapy (ART) is highly effective, durable adherence remains necessary to sustain viral suppression in persons with HIV (PWH). Unfortunately, up to 30-40% of PWH [...]
- Published
- 2021
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50. Metabolic Effects of Preexposure Prophylaxis With Coformulated Tenofovir Disoproxil Fumarate and Emtricitabine
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Glidden, David V, Mulligan, Kathleen, McMahan, Vanessa, Anderson, Peter L, Guanira, Juan, Chariyalertsak, Suwat, Buchbinder, Susan P, Bekker, Linda-Gail, Schechter, Mauro, Grinsztejn, Beatriz, and Grant, Robert M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Obesity ,Clinical Research ,Prevention ,Nutrition ,Clinical Trials and Supportive Activities ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Metabolic and endocrine ,Absorptiometry ,Photon ,Adiposity ,Administration ,Oral ,Adult ,Anti-HIV Agents ,Body Mass Index ,Body Weight ,Double-Blind Method ,Emtricitabine ,Female ,HIV Infections ,Humans ,Lipid Metabolism ,Lipids ,Male ,Pre-Exposure Prophylaxis ,Tenofovir ,Transgender Persons ,Young Adult ,lipids ,lipodystrophy ,tenofovir/emtricitabine ,PrEP ,body composition ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundAntiretroviral drugs have been associated with changes in lipids, fat mass and dat distribution. Tenofovir disoproxil fumarate (TDF) has been shown to have a more favorable metabolic profile than other drugs in its class. However, the metabolic effects of TDF in preexposure prophylaxis (PrEP) are unknown.MethodsWe evaluated the effects of TDF/emtricitabine (FTC) on lipids and body composition in a blinded, placebo-controlled PrEP trial. Participants enrolled in a metabolic subcohort (N = 251, TDF/FTC; N = 247, placebo) consented to fasting lipid panels, dual-energy X-ray absorptiometry scans for body composition, and pharmacologic testing of drug metabolites at baseline and every 24 weeks thereafter.ResultsLean body mass was stable and unaffected by TDF/FTC. Body weight increased in both groups but was lower on TDF/FTC through week 72. This difference was explained by lower fat accumulation on TDF/FTC. The net median percent difference (standard error, P value) for TDF/FTC vs placebo at week 24 was -0.8% (0.4%, P = .02), +0.3% (0.4%, P = .46), and -3.8% (1.4%, P = .009) for total, lean, and fat mass, respectively. There was no apparent differential regional fat accumulation on TDF/FTC. Decreases in cholesterol, but not triglycerides, were seen in TDF/FTC participants, with detectable drug levels compared to placebo.ConclusionsTDF/FTC for PrEP showed cholesterol reductions and appeared to transiently suppress the accumulation of weight and body fat compared to placebo. There was no evidence of altered fat distribution or lipodystrophy during daily oral TDF/FTC PrEP.Clinical trials registrationNCT00458393.
- Published
- 2018
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