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

2020 ◽  
Vol 222 (3) ◽  
pp. 391-395
Author(s):  
Charles Dobard ◽  
Natalia Makarova ◽  
Kenji Nishiura ◽  
Chuong Dinh ◽  
Angela Holder ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Confidence Interval ◽  
Tenofovir Disoproxil Fumarate ◽  
Transmission Model ◽  
Heterosexual Men ◽  
High Efficacy ◽  
Preexposure Prophylaxis ◽  
Immunodeficiency Virus ◽  
Long Acting

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

scholarly journals Projected Impact of Concurrently Available Long-Acting Injectable and Daily-Oral Human Immunodeficiency Virus Preexposure Prophylaxis: A Mathematical Model

2020 ◽  
Vol 223 (1) ◽  
pp. 72-82
Author(s):  
Kevin M Maloney ◽  
Adrien Le Guillou ◽  
Robert A Driggers ◽  
Supriya Sarkar ◽  
Emeli J Anderson ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reference Model ◽  
Reference Scenario ◽  
Substantial Impact ◽  
Population Impact ◽  
Preexposure Prophylaxis ◽  
Immunodeficiency Virus ◽  
Sex With Men ◽  
Long Acting ◽  
The Impact

Abstract Background Long-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. Methods The 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. Results Compared 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. Conclusions If 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.

scholarly journals Is Emtricitabine-Tenofovir Disoproxil Fumarate Pre-exposure Prophylaxis for the Prevention of Human Immunodeficiency Virus Infection Safer Than Aspirin?

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
Noah Kojima ◽  
Jeffrey D. Klausner
Keyword(s):  
Human Immunodeficiency Virus ◽  
Gastrointestinal Bleeding ◽  
Hiv Infection ◽  
Tenofovir Disoproxil Fumarate ◽  
African Women ◽  
Health Study ◽  
Heterosexual Couples ◽  
Preexposure Prophylaxis ◽  
Immunodeficiency Virus ◽  
Exposure Prophylaxis

Abstract Background.  The safety and effectiveness studies of emtricitabine-tenofovir disoproxil fumarate (FTC-TDF) for human immunodeficiency virus (HIV) infection pre-exposure prophylaxis (PrEP) in men and women showed that daily use reduced the risk of HIV acquisition, but there still may concerns about safety. Methods.  A narrative review was done in September 2015 comparing the 5 major studies on PrEP for HIV infection—Preexposure Prophylaxis Initiative (N = 2499; 3324 person-years), Partners Preexposure Prophylaxis (N = 4747; 7830 person-years), TDF2 (N = 1219; 1563 person-years), Preexposure Prophylaxis Trial for HIV Prevention among African Women (N = 2056; 1407 person-years), and Vaginal and Oral Interventions to Control the Epidemic (N = 4969; 5509 person-years)—and the 2 major studies on aspirin safety—Physicians' Health Study (N = 22 071; over 110 000 person-years) and the Women's Health Study (N = 39 876; approximately 400 000 person-years). The numbers needed to harm (NNH) were calculated for FTC-TDF for HIV infection PrEP and aspirin. Results.  The NNH for FTC-TDF in men who have sex with men and transgender women was 114 for nausea and 96 for unintentional weight loss; in heterosexual couples, the NNH was 68 for moderate decreased absolute neutrophil count. For aspirin, the NNH was 909 for major gastrointestinal bleeding, 123 for any gastrointestinal bleeding, and 15 for any bleeding problems in men. In women, the NNH for easy bruising was 10. Conclusions.  We conclude that FTC-TDF for PrEP for HIV infection favorably compares with aspirin in terms of user safety. Although long-term studies are needed, providers should feel reassured about the safety of short- and medium-term PrEP for HIV infection with FTC-TDF.

scholarly journals Changes in Bone Mass After Discontinuation of Preexposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine in Young Men Who Have Sex With Men: Extension Phase Results of Adolescent Trials Network Protocols 110 and 113

2019 ◽  
Vol 70 (4) ◽  
pp. 687-691 ◽  
Author(s):  
Peter L Havens ◽  
Suzanne E Perumean-Chaney ◽  
Amit Patki ◽  
Stacey S Cofield ◽  
Craig M Wilson ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Human Immunodeficiency Virus ◽  
Tenofovir Disoproxil Fumarate ◽  
Network Protocols ◽  
Whole Body ◽  
Mineral Density ◽  
Preexposure Prophylaxis ◽  
Immunodeficiency Virus ◽  
Z Scores ◽  
Sex With Men

AbstractHuman immunodeficiency virus–seronegative men aged 15–22 years who lost bone mineral density (BMD) during tenofovir disoproxil fumarate/emtricitabine preexposure prophylaxis (PrEP) showed BMD recovery 48 weeks following PrEP discontinuation. Lumbar spine and whole body BMD z-scores remained below baseline 48 weeks off PrEP in participants aged 15–19 years.Clinical Trials Registration. NCT01772823 (ATN 110) and NCT01769456 (ATN 113).

scholarly journals Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide for Human Immunodeficiency Virus Preexposure Prophylaxis at a Boston Community Health Center

2021 ◽  
Vol 8 (8) ◽  
Author(s):  
Julia L Marcus ◽  
Kenneth Levine ◽  
Whitney C Sewell ◽  
Patricia Solleveld ◽  
Kenneth H Mayer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Human Immunodeficiency Virus ◽  
Cardiovascular Risk ◽  
Creatinine Clearance ◽  
Cardiovascular Risk Factors ◽  
Tenofovir Disoproxil Fumarate ◽  
Community Health Center ◽  
Preexposure Prophylaxis ◽  
Immunodeficiency Virus ◽  
Tenofovir Alafenamide

Abstract Background Efforts 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. Methods The 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). Results Of 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. Conclusions Few 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.

Failure to Identify Human Immunodeficiency Virus-Seropositive Newborns: Epidemiology and Enrollment Patterns in a Predominantly White, Nonurban Setting

PEDIATRICS ◽  
1995 ◽  
Vol 96 (6) ◽  
pp. 1083-1089
Author(s):  
James Coplan ◽  
Timothy D. Dye ◽  
Kathie A. Contello ◽  
Coleen K. Cunningham ◽  
Kim Kirkwood ◽  
...  
Keyword(s):  
New York ◽  
Human Immunodeficiency Virus ◽  
Confidence Interval ◽  
Predominantly White ◽  
Pediatric Aids ◽  
Immunodeficiency Virus ◽  
Enrollment Rates ◽  
First 90 Days ◽  
Onondaga County ◽  
Hiv Seropositive

Objective. To describe the epidemiology of newborn seroprevalence for human immunodeficiency virus (HIV) in a predominantly white, nonurban population, and to determine the factors associated with enrollment at a regional pediatric acquired immunodeficiency syndrome (AIDS) center serving that population. Design. Retrospective case series of children enrolled at a regional pediatric AIDS center during a 6-year period and comparison with universal blind newborn screening data collected by the state of New York during the same time interval. Setting. The Pediatric AIDS Center at State University of New York-Health Science Center at Syracuse, which serves as the only source of HIV-related pediatric care for children in a 16-county region of upstate New York totaling 1.8 million population. Results. One hundred thirty-nine HIV-seropositive infants were born in the region during the 6-year study period; complete blind screening data were available for 138. Sixty-five (47%) of these infants were white. Thirty-nine (28%) of 138 had been enrolled at the Pediatric AIDS Center within the first 90 days of life. An additional 22 (16%) were enrolled at older than 90 days of life. The remaining 77 (56%) have never been seen at the center and are presumed to be unidentified. County enrollment rates varied from 0% to 100% and correlated with percent nonwhite births (r = .58; 95% confidence interval, 0.04-0.86). Children in outlying counties were at greater risk for nonenrollment than children from Onondaga County (site of the Pediatric AIDS Center) (adjusted relative risk, 1.38; 95% confidence interval, 1.05-1.85). White infants residing outside of Onondaga County were at the greatest risk of nonenrollment; of 50 seropositive white infants residing outside of Onondaga County, only 7(14%) were enrolled at the center within the first 90 days of life. Conclusions. Local demographic factors can skew the racial distribution of HIV-seropositive infants dramatically compared with the national experience. White race and residence in counties away from the medical center each constituted risk factors for nonenrollment at the Pediatric AIDS Center. The epidemiology of HIV in this predominantly white, rural population, coupled with physician practices, probably contributed to low identification and enrollment rates. As the AIDS epidemic spreads into similar populations elsewhere, HIV infection in pregnant women or newborn infants is likely to become progressively harder to detect, unless universal screening is adopted.

scholarly journals A Randomized Switch From Nevirapine-Based Antiretroviral Therapy to Single Tablet Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in Virologically Suppressed Human Immunodeficiency Virus-1-Infected Rwandans

2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Sean E. Collins ◽  
Philip M. Grant ◽  
Francois Uwinkindi ◽  
Annie Talbot ◽  
Eric Seruyange ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Tenofovir Disoproxil Fumarate ◽  
Sub Saharan Africa ◽  
Current Therapy ◽  
Virologic Suppression ◽  
Open Label ◽  
Immunodeficiency Virus ◽  
Sub Saharan ◽  
Hiv 1

Abstract Background.  Many human immunodeficiency virus (HIV)-infected patients remain on nevirapine-based antiretroviral therapy (ART) despite safety and efficacy concerns. Switching to a rilpivirine-based regimen is an alternative, but there is little experience with rilpivirine in sub-Saharan Africa where induction of rilpivirine metabolism by nevirapine, HIV subtype, and dietary differences could potentially impact efficacy. Methods.  We conducted an open-label noninferiority study of virologically suppressed (HIV-1 ribonucleic acid [RNA] < 50 copies/mL) HIV-1-infected Rwandan adults taking nevirapine plus 2 nucleos(t)ide reverse-transcriptase inhibitors. One hundred fifty participants were randomized 2:1 to switch to coformulated rilpivirine-emtricitabine-tenofovir disoproxil fumarate (referenced as the Switch Arm) or continue current therapy. The primary efficacy endpoint was HIV-1 RNA < 200 copies/mL at week 24 assessed by the US Food and Drug Administration Snapshot algorithm with a noninferiority margin of 12%. Results.  Between April and September 2014, 184 patients were screened, and 150 patients were enrolled; 99 patients switched to rilpivirine-emtricitabine-tenofovir, and 51 patients continued their nevirapine-based ART. The mean age was 42 years and 43% of participants were women. At week 24, virologic suppression (HIV-1 RNA level <200 copies/mL) was maintained in 93% and 92% in the Switch Arm versus the continuation arm, respectively. The Switch Arm was noninferior to continued nevirapine-based ART (efficacy difference 0.8%; 95% confidence interval, −7.5% to +12.0%). Both regimens were generally safe and well tolerated, although 2 deaths, neither attributed to study medications, occurred in participants in the Switch Arm. Conclusions.  A switch from nevirapine-based ART to rilpivirine-emtricitabine-tenofovir disoproxil fumarate had similar virologic efficacy to continued nevirapine-based ART after 24 weeks with few adverse events.

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