A taxonomy of pragmatic measures of HIV preexposure prophylaxis use.
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ABSTRACT: Objectives
As delivery of preexposure prophylaxis (PrEP) becomes an HIV prevention priority in the United States, standard, pragmatic measures of PrEP use are needed to compare and evaluate prevention implementation programs. By using readily available electronic health record data, we describe and compare measures of persistence and retention.Design
Retrospective cohort.Methods
Using electronic health record prescription data for patients at a large urban Federally Qualified Health Center from 2015 to 2019, we calculated measures of persistence and retention and compared them to pharmacy claims data, PrEP biomarkers, and HIV outcomes.Results
Total PrEP time was 19.8 months on average. During this period, average adherence by medication prescription ratio (MRxR) was 89%; 77% of patients had an MRxR at least 85% and 90% have an MRxR at least 57%. Over the first 6 months, average proportion of days covered (PDC) at least 85% was 53% and PDC at least 57% was 57%. Prescription fill rates, based on claims data from a pharmacy partner, ranged from 45 to 60%. Using tenofovir-diphosphate as the gold standard, PDC had high sensitivity (97%) but low specificity (≤13%). As a measure of retention, over the first 6 months, 59% of patients had quarterly HIV tests.Conclusion
Total PrEP time is useful measure of overall persistence, while PDC can assess persistence and adherence at a specific time point. Adherence by PDC is more conservative compared with MRxR; both will overestimate true adherence. Retention in care can be measured by quarterly HIV tests. Using consistent terminology and reporting timepoints and adherence thresholds will help reporting and comparing PrEP delivery programs.
SUBMITTER: Pyra M
PROVIDER: S-EPMC7856306 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:HIV-testing algorithms for preexposure prophylaxis (PrEP) should be optimized to minimize the risk of drug resistance, the time off PrEP required to evaluate false-positive screening results, and costs and to expedite the start of therapy for those confirmed to be infected. HIV rapid tests (RTs) for anti-HIV antibodies provide results in less than 1 h and can be conducted by nonlicensed staff at the point of care. In many regions, Western blot (WB) testing is required to confirm reactive RT results. WB testing, however, causes delays in diagnosis and adds expense. The iPrEx study evaluated the safety and efficacy of daily oral emtricitabine-tenofovir disoproxil fumarate among HIV-seronegative men and transgender women who have sex with men: HIV infection was assessed with two RTs plus WB confirmation, followed by HIV-1 plasma viral load testing. During the iPrEx study, there were 51,260 HIV status evaluations among 2,499 volunteers using RTs: 142 (0.28%) had concordant positive results (100% were eventually confirmed) and 19 (0.04%) had discordant results among 14 participants; 11 were eventually determined to be HIV infected. A streamlined approach using only one RT to screen and a second RT to confirm (without WB) would have had nearly the same accuracy. Discrepant RT results are best evaluated with nucleic acid testing, which would also increase sensitivity.
| S-EPMC4290918 | biostudies-literature
Project description:The review describes the evidence for HIV preexposure prophylaxis (PrEP) with daily combined tenofovir disoproxil fumarate and emtricitabine for adolescents and young adults. Current recommendations are described, as are the unique medical, socioeconomic, and legal considerations regarding the use of PrEP for youth.PrEP with daily oral tenofovir disoproxil fumarate-emtricitabine has been shown to help prevent new HIV infection among adults at substantial risk. Evidence suggests a protective benefit of PrEP for youth at risk for HIV, although low adherence is emerging as a barrier to effective use.Effective use of antiretrovirals for PrEP represents a seminal development in HIV prevention efforts. Improving access and adherence to PrEP for youth has the potential to substantially reduce the incidence of HIV in this population.
| S-EPMC5762125 | biostudies-other
Project description:Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others.In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety.HIV infections occurred in 33 women in the TDF-FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P=0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group (P=0.04, P<0.001, and P=0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group (4.7%) than in the placebo group (3.0%, P=0.051). Less than 40% of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion. The study was stopped early, on April 18, 2011, because of lack of efficacy.Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low. (Supported by the U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov number, NCT00625404.).
| S-EPMC3687217 | biostudies-literature
Project description:BACKGROUND:Publicly funded HIV-testing sites can identify HIV preexposure prophylaxis (PrEP) candidates and provide PrEP linkage. SETTING:Harris Health System's HIV clinic, HIV-testing program, and HIV-prevention program (HPP) in Houston, TX, a high HIV-incidence city. METHODS:A prospective assessment of individuals aged 18 years and older recruited from walk-in HIV testing from December 2013 to April 2015 included risk assessment, HIV testing, and self-administered survey, with follow-up surveys at 6 and 12 months and medical record review. RESULTS:The mean age of our sample (n = 300) was 38.3 ± 11.7 years. Men constituted 63.1% of the sample and 53.7% were black non-Hispanic, 26.3% Hispanic, and 14.7% white non-Hispanic. Most were uninsured (63.5%). Only 27% always used condoms, although 67% perceived personal HIV risk. Of 300 participants, 64 (21.3%) linked to PrEP care and 49 (16.3%) took PrEP. In multivariable analysis, compared with heterosexual men, women [adjusted OR (aOR) 4.1, 95% CI: 1.5 to 11.1] and MSM (aOR 10.2, 95% CI: 3.4 to 31.0) were more likely to attend HPP and to take PrEP (aOR 3.0, 95% CI: 1.6 to 15.1 and 3.0, 95% CI: 1.1 to 8.3, respectively). Serodiscordance and PrEP interest correlated with program attendance (aOR 14.0, 95% CI: 6.1 to 32.3 and aOR 6.7, 95% CI: 1.8 to 25.4) and taking PrEP (aOR 13.1, 95% CI: 5.2 to 32.8 and 14.4, 95% CI: 1.8 to 166.9), respectively. CONCLUSIONS:Preexposure prophylaxis interest, being female or MSM, and serodiscordance correlated with PrEP linkage. Safety-net health systems can facilitate PrEP access in marginalized populations, but the PrEP initiation rates remain low.
| S-EPMC5949071 | biostudies-literature
Project description:ImportanceAlthough HIV preexposure prophylaxis (PrEP) implementation among persons who inject drugs has been inadequate, national HIV monitoring programs do not include data on PrEP, and specific trends in PrEP use are not well understood.ObjectiveTo estimate HIV PrEP uptake among commercially insured persons with opioid or stimulant use disorder by injection drug use (IDU) status.Design, setting, and participantsThis cross-sectional study used deidentified data from the MarketScan Commercial Claims and Encounters Database to identify a sample of 547 709 commercially insured persons without HIV but with opioid and/or stimulant use disorder, including 110 592 with evidence of IDU between January 1, 2010, and December 31, 2019. Data were analyzed from November 1, 2020, to July 1, 2021.ExposuresPersons with opioid and/or stimulant use disorder and evidence of IDU were identified through claims data.Main outcomes and measuresThe outcome was receipt of tenofovir disoproxil fumarate and emtricitabine for PrEP as identified from filled pharmacy claims. Multivariable logistic regression was used to assess the association of demographic and clinical characteristics with receipt of PrEP.ResultsThe study cohort included 211 609 (28.6%) females and 336 100 (61.4%) males with a combined mean (SD) age of 34.8 (13.1) years, including 110 592 individuals with evidence of IDU. During the study period, 508 (0.09%) persons with opioid and/or stimulant use disorder, including 170 (0.15%) with evidence of IDU, received PrEP. Receipt of PrEP increased from 0.001 to 0.243 per 100 person-years from 2010 through 2019 among the entire cohort and from 0.000 to 0.295 per 100 person-years among those with IDU. In multivariable analysis, PrEP use was more likely among males (adjusted odds ratio [aOR] 8.72; 95% CI, 6.39-11.89), persons with evidence of IDU (aOR, 1.47; 95% CI, 1.21-1.79), and persons with evidence of sexual risk indications for PrEP (aOR, 23.68; 95% CI, 19.57-28.66).Conclusions and relevanceIn this cross-sectional study of commercially insured persons with opioid and/or stimulant use disorder, HIV PrEP delivery remained low, including among those with evidence of IDU. PrEP should be consistently offered alongside substance use disorder treatment and other harm reduction and HIV prevention services.
| S-EPMC9277489 | biostudies-literature
Project description:Purpose of reviewTo review current laboratory and clinical data on the frequency and relative risk of drug resistance and range of mutations selected from approved and investigational antiretroviral agents used for preexposure prophylaxis (PrEP) of HIV-1 infection, including tenofovir disproxil fumarate (TDF)-based oral PrEP, dapivirine ring, injectable cabotegravir (CAB), islatravir, lenacapavir and broadly neutralizing antibodies (bNAbs).Recent findingsThe greatest risk of HIV-1 resistance from PrEP with oral TDF/emtricitabine (FTC) or injectable CAB is from starting or continuing PrEP after undiagnosed acute HIV infection. By contrast, the dapivirine intravaginal ring does not appear to select nonnucleoside reverse transcriptase inhibitor resistance in clinical trial settings. Investigational inhibitors including islatravir, lenacapavir, and bNAbs are promising for use as PrEP due to their potential for sustained delivery and low risk of cross-resistance to currently used antiretrovirals, but surveillance for emergence of resistance mutations in more HIV-1 gene regions (gag, env) will be important as the same drugs are being developed for HIV therapy.SummaryPrEP is highly effective in preventing HIV infection. Although HIV drug resistance from PrEP use could impact future options in individuals who seroconvert on PrEP, the current risk is low and continued monitoring for the emergence of resistance and cross-resistance during product development, clinical studies, and product roll-out is advised to preserve antiretroviral efficacy for both treatment and prevention.
| S-EPMC9245149 | biostudies-literature
Project description:ImportanceLong-term follow-up is needed to evaluate gaps in HIV preexposure prophylaxis (PrEP) care delivery and to identify individuals at risk for falling out of care.ObjectiveTo characterize the PrEP continuum of care, including prescription, initiation, discontinuation, and reinitiation, and evaluate incident HIV infections.Design, setting, and participantsThis retrospective cohort study used data from the electronic health records (EHR) at Kaiser Permanente Northern California to identify individuals aged 18 years and older who received PrEP care between July 2012 and March 2019. Individuals were followed up from date of linkage (defined as a PrEP referral or PrEP-coded encounter) until March 2019, HIV diagnosis, discontinuation of health plan membership, or death. Data were analyzed from December 2019 to January 2021.ExposuresSociodemographic factors included age, sex, race and ethnicity, and neighborhood deprivation index, and clinical characteristics were extracted from the EHR.Main outcomes and measuresThe primary outcomes were attrition at each step of the PrEP continuum of care and incident HIV infections.ResultsAmong 13 906 individuals linked to PrEP care, the median (interquartile range [IQR]) age was 33 (27-43) years, 6771 individuals (48.7%) were White, and 13 227 (95.1%) were men. Total follow-up was 26 210 person-years (median [IQR], 1.6 [0.7-2.8] years). Of individuals linked to PrEP care, 88.1% (95% CI, 86.1%-89.9%) were prescribed PrEP and of these, 98.2% (95% CI, 97.2%-98.8%) initiated PrEP. After PrEP initiation, 52.2% (95% CI, 48.9%-55.7%) discontinued PrEP at least once during the study period, and 60.2% (95% CI, 52.2%-68.3%) of these individuals subsequently reinitiated. Compared with individuals aged 18 to 25 years, older individuals were more likely to receive a PrEP prescription (eg, age >45 years: hazard ratio [HR], 1.21 [95% CI, 1.14-1.29]) and initiate PrEP (eg, age >45 years: HR, 1.09 [95% CI, 1.02-1.16]) and less likely to discontinue (eg, age >45 years: HR, 0.46 [95% CI, 0.42-0.52]). Compared with White patients, African American and Latinx individuals were less likely to receive a PrEP prescription (African American: HR, 0.74 [95% CI, 0.69-0.81]; Latinx: HR, 0.88 [95% CI, 0.84-0.93]) and initiate PrEP (African American: HR, 0.87 [95% CI, 0.80-0.95]; Latinx: HR, 0.90 [95% CI, 0.86-0.95]) and more likely to discontinue (African American: HR, 1.36 [95% CI, 1.17-1.57]; Latinx: 1.33 [95% CI, 1.22-1.46]). Similarly, women, individuals with lower neighborhood-level socioeconomic status (SES), and persons with a substance use disorder (SUD) were less likely to be prescribed (women: HR, 0.56 [95% CI, 0.50-0.62]; lowest SES: HR, 0.72 [95% CI, 0.68-0.76]; SUD: HR, 0.88 [95% CI, 0.82-0.94]) and initiate PrEP (women: HR, 0.71 [95% CI, 0.64-0.80]; lower SES: HR, 0.93 [95% CI, 0.87-.0.99]; SUD: HR, 0.88 [95% CI, 0.81-0.95]) and more likely to discontinue (women: HR, 1.99 [95% CI, 1.67-2.38]); lower SES: HR, 1.40 [95% CI, 1.26-1.57]; SUD: HR, 1.23 [95% CI, 1.09-1.39]). HIV incidence was highest among individuals who discontinued PrEP and did not reinitiate PrEP (1.28 [95% CI, 0.93-1.76] infections per 100 person-years).Conclusions and relevanceThese findings suggest that gaps in the PrEP care continuum were concentrated in populations disproportionately impacted by HIV, including African American individuals, Latinx individuals, young adults (aged 18-25 years), and individuals with SUD. Comprehensive strategies to improve PrEP continuum outcomes are needed to maximize PrEP impact and equity.
| S-EPMC8391097 | biostudies-literature
Project description:Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection.We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly.Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P=0.004). We observed no significant differences in the frequencies of other adverse events.None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low. (Funded by the National Institutes of Health; VOICE ClinicalTrials.gov number, NCT00705679.).
| S-EPMC4341965 | biostudies-literature
Project description:BackgroundThe iPrEx study demonstrated that combination oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) as preexposure prophylaxis (PrEP) protects against HIV acquisition in men who have sex with men and transgender women. Selection for drug resistance could offset PrEP benefits.MethodsPhenotypic and genotypic clinical resistance assays characterized major drug resistant mutations. Minor variants with FTC/TDF mutations K65R, K70E, M184V/I were measured using 454 deep sequencing and a novel allele-specific polymerase chain reaction (AS-PCR) diagnostic tolerant to sequence heterogeneity.ResultsControl of primer-binding site heterogeneity resulted in improved accuracy of minor variant measurements by AS-PCR. Of the 48 on-study infections randomized to FTC/TDF, none showed FTC/TDF mutations by clinical assays despite detectable drug levels in 8 participants. Two randomized to FTC/TDF had minor variant M184I detected at 0.53% by AS-PCR or 0.75% by deep sequencing, only 1 of which had low but detectable drug levels. Among those with acute infection at randomization to FTC/TDF, M184V or I mutations that were predominant at seroconversion waned to background levels within 24 weeks after discontinuing drug.ConclusionsDrug resistance was rare in iPrEx on-study FTC/TDF-randomized seroconverters, and only as low-frequency minor variants. FTC resistance among those initiating PrEP with acute infection waned rapidly after drug discontinuation. Clinical Trials Registration.NCT00458393.
| S-EPMC4176446 | biostudies-literature
Project description:The administration of antiretrovirals before HIV exposure to prevent infection (i.e., preexposure prophylaxis; PrEP) is under evaluation in clinical trials. Because PrEP is based on antiretrovirals, there is considerable concern that it could substantially increase transmitted resistance, particularly in resource-rich countries. Here we use a mathematical model to predict the effect of PrEP interventions on the HIV epidemic in the men-who-have-sex-with-men community in San Francisco. The model is calibrated using Monte Carlo filtering and analyzed by constructing nonlinear response hypersurfaces. We predict PrEP interventions could substantially reduce transmission but significantly increase the proportion of new infections caused by resistant strains. Two mechanisms can cause this increase. If risk compensation occurs, the proportion increases due to increasing transmission of resistant strains and decreasing transmission of wild-type strains. If risk behavior remains stable, the increase occurs because of reduced transmission of resistant strains coupled with an even greater reduction in transmission of wild-type strains. We define this as the paradox of PrEP (i.e., resistance appears to be increasing, but is actually decreasing). We determine this paradox is likely to occur if the efficacy of PrEP regimens against wild-type strains is greater than 30% and the relative efficacy against resistant strains is greater than 0.2 but less than the efficacy against wild-type. Our modeling shows, if risk behavior increases, that it is a valid concern that PrEP could significantly increase transmitted resistance. However, if risk behavior remains stable, we find the concern is unfounded and PrEP interventions are likely to decrease transmitted resistance.
| S-EPMC2901470 | biostudies-other