Novel Approaches for Development of Human Immunodeficiency Virus Preexposure Prophylaxis Agents.
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ABSTRACT:
SUBMITTER: Cohen MS
PROVIDER: S-EPMC6936000 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo understand perspectives on and preferences for preexposure prophylaxis (PrEP) for pregnant individuals who are at risk for human immunodeficiency virus (HIV) infection.MethodsIn this qualitative study, we purposively sampled and conducted in-depth interviews with pregnant participants at risk of HIV infection (indicated by a recent sexually transmitted infection [STI]) from a U.S. urban obstetrics clinic. Interview questions focused on perceived HIV risk, knowledge and perceptions of PrEP, and preferences for different PrEP formulations. We coded data using deductive and inductive codes, created matrices to explore patterns in findings, and wrote memos to interpret emergent themes.ResultsTwenty patients were enrolled. Median age of the participants was 24 years (interquartile range 19-26 years), 95.0% were African American, 65.0% were high school graduates, and 70.0% had unplanned pregnancies. Participants had low knowledge of PrEP and most saw themselves at low to no risk of HIV acquisition, despite their recent STI. Further, participants' low HIV risk perception and medication safety concerns reduced PrEP acceptability. Moreover, very few had discussed PrEP with their obstetrician-gynecologists (ob-gyns) during antenatal care, which further affected perceived acceptability. However, participants who did discuss PrEP with their ob-gyns had favorable perceptions of it. These participants indicated that they would choose a formulation based on individual preferences, which were largely shaped by perceived ease of use, acceptability, and prior experience with other medication regimens.ConclusionObstetrician-gynecologists may play an important role in increasing pregnant individuals' knowledge of and access to PrEP during pregnancy among those who are at risk of HIV acquisition. To maximize uptake and adherence during this time, PrEP formulations should be tailored to individual preferences. Prevention of HIV during this critical life transition is important not only for the long-term health and well-being of pregnant individuals and their infants, but to the plan to end the HIV epidemic in the United States by 2030.
| S-EPMC9627543 | biostudies-literature
Project description:Feminizing hormone therapy (FHT) may interact with human immunodeficiency virus preexposure prophylaxis (PrEP). We found that transgender women who took FHT exhibited a 7-fold lower rectal tissue ratio of PrEP's active metabolites vs competing deoxynucleotides compared to cisgender women and men (P = .03) that inversely correlated with estradiol (? = -0.79; P < .05). Thus, FHT may negatively impact PrEP efficacy. Clinical Trials Registration . NCT02983110.
| S-EPMC7188232 | biostudies-literature
Project description:BackgroundLong-acting injectable (LAI) human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) is reportedly efficacious, although full trial results have not been published. We used a dynamic network model of HIV transmission among men who have sex with men to assess the population impact of LAI-PrEP when available concurrently with daily-oral (DO) PrEP.MethodsThe reference model represents the current HIV epidemiology and DO-PrEP coverage (15% among those with behavioral indications for PrEP) among men who have sex with men in the southeastern United States. Primary analyses investigated varied PrEP uptake and proportion selecting LAI-PrEP. Secondary analyses evaluated uncertainty in pharmacokinetic efficacy and LAI-PrEP persistence relative to DO-PrEP.ResultsCompared with the reference scenario, if 50% chose LAI-PrEP, 4.3% (95% simulation interval, -7.3% to 14.5%) of infections would be averted over 10 years. The impact of LAI-PrEP is slightly greater than that of the DO-PrEP-only regimen, based on assumptions of higher adherence and partial protection after discontinuation. If the total PrEP initiation rate doubled, 17.1% (95% simulation interval, 6.7%-26.4%) of infections would be averted. The highest population-level impact occurred when LAI-PrEP uptake and persistence improved.ConclusionsIf LAI-PrEP replaces DO-PrEP, its availability will modestly improve the population impact. LAI-PrEP will make a more substantial impact if its availability drives higher total PrEP coverage, or if persistence is greater for LAI-PrEP.
| S-EPMC7781468 | biostudies-literature
Project description:BackgroundThe human immunodeficiency virus (HIV) epidemic in India is concentrated among 3.1 million men who have sex with men (MSM) and 1.1 million people who inject drugs (PWID), with a mean incidence of 0.9-1.4 per 100 person-years. We examined the cost-effectiveness of both preexposure prophylaxis (PrEP) and HIV testing strategies for MSM and PWID in India.MethodsWe populated an HIV microsimulation model with India-specific data and projected clinical and economic outcomes of 7 strategies for MSM/PWID, including status quo; a 1-time HIV test; routine HIV testing every 3, 6, or 12 months; and PrEP with HIV testing every 3 or 6 months. We used a willingness-to-pay threshold of US$1950, the 2017 Indian per capita gross domestic product, to define cost-effectiveness.ResultsHIV testing alone increased life expectancy by 0.07-0.30 years in MSM; PrEP added approximately 0.90 life-years to status quo. Results were similar in PWID. PrEP with 6-month testing was cost-effective for both MSM (incremental cost-effectiveness ratio [ICER], $1000/year of life saved [YLS]) and PWID (ICER, $500/YLS). Results were most sensitive to HIV incidence. PrEP with 6-month testing would increase HIV-related expenditures by US$708 million (MSM) and US$218 million (PWID) over 5 years compared to status quo.ConclusionsWhile the World Health Organization recommends PrEP with quarterly HIV testing, our analysis identifies PrEP with semiannual testing as the cost-effective HIV prevention strategy for Indian MSM and PWID. Since nationwide scale-up would require a substantial fiscal investment, areas of highest HIV incidence may be the appropriate initial targets for PrEP scale-up.
| S-EPMC7319272 | biostudies-literature
Project description:BackgroundEfforts to end the human immunodeficiency virus (HIV) epidemic may be threatened if limited preexposure prophylaxis (PrEP) resources are funneled from tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) to tenofovir alafenamide with emtricitabine (TAF/FTC) without proportional clinical benefits.MethodsThe study population was patients at a Boston community health center who were assigned male sex at birth, aged ≥18 years, and prescribed TDF/FTC for PrEP in the 12 months before TAF/FTC approval (October 2019). We determined the frequency of switching to TAF/FTC in the 12 months after approval, including clinically indicated switching (ie, creatinine clearance <60 mL/minute or reduced bone density), potentially unnecessary switching (ie, no indications for switching and no cardiovascular risk factors), and potentially harmful switching (ie, no indications for switching and either obesity or dyslipidemia).ResultsOf 2892 TDF/FTC users, mean age was 38 years, 96.0% were cisgender men, and 78.9% were white. A total of 343 (11.9%) switched to TAF/FTC. Based on documented renal, bone, and cardiovascular risk factors, we identified 24 (7.0%) with clinically indicated switching, 271 (79.0%) with potentially unnecessary switching, and 48 (14.0%) with potentially harmful switching. When indications for switching additionally included hypertension, diabetes, and creatinine clearance 60-70 mL/minute, 27.1% of switching was clinically indicated.ConclusionsFew who switched to TAF/FTC had documented indications for switching, although some appear to have been switched in anticipation of indications developing. As generic TDF/FTC is further discounted, provider education and patient decision aids are needed to facilitate selection of PrEP medications that is both clinically sound and cost-effective.
| S-EPMC8496521 | biostudies-literature
Project description:BackgroundDaily dosing of tenofovir disoproxil fumarate, with or without emtricitabine, has high efficacy in preventing human immunodeficiency virus (HIV) infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration.MethodsParticipant data from TFV-based daily oral and topical active arms of phase 3 trials (iPrEx, VOICE, and Partners PrEP) were pooled (n = 2950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models.ResultsAround 50% of the individuals were estimated to be adherent, which differed from self-reported adherence (∼90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high-risk females (45.8 ng/mL) compared with high-risk males (16.1 ng/mL) and to low-risk individuals (∼7.5 ng/mL). Dosing simulations indicated that high-risk women require full adherence to maintain protective levels.ConclusionsUsing the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high-risk females need higher levels of plasma TFV to achieve HIV protection compared with males. HIV protection exceeds 90% in all populations if daily adherence is achieved.
| S-EPMC10139701 | biostudies-literature
Project description:BackgroundPreexposure prophylaxis (PrEP) is highly effective for preventing human immunodeficiency virus (HIV) infection, but risk compensation (RC) in men who have sex with men (MSM) raises concerns about increased sexually transmitted infections (STIs). The Center for Disease Control and Prevention's (CDC's) PrEP guidelines recommend biannual STI screening, which may reduce incidence by treating STIs that would otherwise remain undiagnosed. We investigated these two counteracting phenomena.MethodsWith a network-based mathematical model of HIV, Neisseria gonorrhoeae (NG), and Chlamydia trachomatis (CT) transmission dynamics among MSM in the United States, we simulated PrEP uptake following the prescription indications and HIV/STI screening recommendations in the CDC guidelines. Scenarios varied PrEP coverage (the proportion of MSM indicated for PrEP who received it), RC (a reduction in the per-act probability of condom use), and the STI screening interval.ResultsIn our reference scenario (40% coverage, 40% RC), 42% of NG and 40% of CT infections would be averted over the next decade. A doubling of RC would still result in net STI prevention relative to no PrEP. STIs declined because PrEP-related STI screening resulted in a 17% and 16% absolute increase in the treatment of asymptomatic and rectal STIs, respectively. Screening and timely treatment at quarterly vs biannual intervals would reduce STI incidence an additional 50%.ConclusionsImplementation of the CDC PrEP guidelines while scaling up PrEP coverage could result in a significant decline in STI incidence among MSM. Our study highlights the design of PrEP not only as antiretroviral medication but as combination HIV/STI prevention incorporating STI screening.
| S-EPMC5848234 | biostudies-literature
Project description:BackgroundTenofovir alafenamide fumarate (TAF) was promoted as a safer alternative to tenofovir disoproxil fumarate (TDF) for human immunodeficiency virus oral preexposure prophylaxis (PrEP). It is unknown if switching from TDF to TAF translates to improved renal function. We used electronic health record (EHR) data to assess changes in creatinine-estimated glomerular filtration rate (eGFR) after switching from TDF to TAF.MethodsWe conducted a retrospective cohort study using EHR data from Kaiser Permanente Southern California. We identified individuals who switched from TDF to TAF between October 2019 and May 2022 and used time-varying propensity score matching to identify controls who were on TDF ("nonswitchers"). We then used Bayesian longitudinal modeling to compare differences in eGFR between switching and nonswitching scenarios.ResultsAmong 5246 eligible individuals, we included 118 TDF to TAF switchers and 114 nonswitchers. Compared to nonswitchers, switchers had older age of starting TDF but similar body weights at index date. A higher proportion of switchers were White, on Medicare or Medicaid, and had dyslipidemia at index date. Switching to TAF was associated with a higher eGFR compared to staying on TDF in 3-15 months post-switch, but the differences were not statistically significant (eg, month 9 difference: 1.27 [95% credible interval, -1.35 to 3.89]). While most of the estimated changes showed eGFR increase associated with switching, most were <2 eGFR units. Sensitivity analyses to address missingness or nonadherence showed similar results.ConclusionsSwitching from TDF to TAF for PrEP was associated with a nonsignificant increase in eGFR. Findings need to be confirmed using larger cohorts.
| S-EPMC10863550 | biostudies-literature
Project description:BackgroundHuman immunodeficiency virus (HIV) testing is the first step in the HIV prevention cascade. The Centers for Disease Control and Prevention HIV laboratory diagnostic testing algorithm was developed before preexposure prophylaxis (PrEP) and immediate antiretroviral therapy (iART) became standards of care. PrEP and iART have been shown to delay antibody development and affect the performance of screening HIV assays. Quantitative results from fourth-generation HIV testing may be helpful to disambiguate HIV testing.MethodsWe retrospectively reviewed 38 850 results obtained at an urban, academic medical center. We assessed signal-to-cutoff (s/co) distribution among positive and negative tests, in patients engaged and not engaged in an HIV prevention program, and evaluated changes in patients with multiple results. Classification and regression tree (CART) analysis was used to determine a threshold cutoff, and logistic regression was used to identify predictors of true positive tests.ResultsNinety-seven percent of patients with a negative HIV test had a result that was ≤0.2 s/co. For patients tested more than once, we found differences in s/co values did not exceed 0.2 s/co for 99.2% of results. CART identified an s/co value, 38.78, that in logistic regression on a unique validation cohort remained associated with the likelihood of a true-positive HIV result (odds ratio, 2.49).ConclusionsMachine-learning methods may be used to improve HIV screening by automating and improving interpretations, incorporating them into robust algorithms, and improving disease prediction. Further investigation is warranted to confirm if s/co values combined with a patient's risk profile will allow for better clinical decision making for individuals on PrEP or eligible for iART.
| S-EPMC9290571 | biostudies-literature
Project description:BackgroundHuman immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) has helped reduce new HIV infections. However, bacterial sexually transmitted infections (STIs) have increased among PrEP users. We examined PrEP knowledge, access, and risk perceptions in an age of antimicrobial resistance (AMR).MethodsAn online anonymous survey was distributed to all cisgender men/transpersons who have sex with men attending a sexual health clinic in Bristol, United Kingdom (October 2018 to November 2019). Interviews with a sample identified at increased risk of HIV were analyzed thematically and integrated with survey data.ResultsFive hundred and seventy-eight (95%) of 617 cisgender men/transpersons who have sex with men survey respondents were HIV-negative/unknown, of these, 202 (34.9%) had ever used PrEP. Interviewees (n = 24) reported widespread awareness of and enthusiasm for PrEP. Among nonusers, 39% (146/376) were unaware how to access PrEP, and 27% (103/376) could not access PrEP through the national "impact" trial of whom 79% (81/103) were eligible. The PrEP was described as "life-changing," but expense was the main barrier to use. Sixty-two percent (358/578) of HIV-negative/unknown respondents on PrEP were more likely to have condomless anal intercourse with someone they thought was HIV-negative. Interviewees used PrEP with other risk-reduction strategies. Sexually transmitted infections were seen as "curable" and AMR rarely influenced risk perception or sexual decision making.ConclusionsThe PrEP awareness was high, but purchase cost limited access. PrEP may increase condomless anal intercourse, but interviewees used PrEP as one of many risk-reduction tools. Reduced fear of HIV transmission and testing was highly valued. Sexually transmitted infection AMR was not seen as an immediate threat and did not influence risk perception or sexual decision making.
| S-EPMC8360657 | biostudies-literature