Broadly neutralizing antibody-mediated protection against simian-HIV infection among macaques with vaginal sexually transmitted infections.

Objective: Sexually transmitted infections (STIs) increase mucosal HIV infection risk and have the potential to reduce preexposure prophylaxis efficacy. Clinical trials of a broadly neutralizing antibody (bNAb) provided proof-of-concept that passive immunization against HIV can be efficacious in people. We sought to evaluate preclinically the protective efficacy of passive bNAb immunization against simian-human immunodeficiency virus (SHIV) infection in the context of concurrent vaginal STIs.

Broadly neutralizing antibody-mediated protection of macaques against repeated intravenous exposures to simian-human immunodeficiency virus.

Objective: The opioid epidemic has increased parentally acquired HIV infection. To inform the development of a long-acting prevention strategy, we evaluated the protective efficacy of broadly neutralizing antibodies (bNAbs) against intravenous simian-human immunodeficiency virus (SHIV) infection in macaques.

Design: Five cynomolgus macaques were injected once subcutaneously with 10-1074 and 3BNC117 (10 mg each kg-1) and were repeatedly challenged intravenously once weekly with SHIVAD8-EO (130 TCID50), until infection was confirmed via plasma viral load assay.

Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection.

A long-acting injectable formulation of the HIV integrase inhibitor cabotegravir (CAB-LA) is currently in clinical development for PrEP. Although the long plasma half-life of CAB-LA is an important attribute for PrEP, it also raises concerns about drug resistance emergence if someone becomes infected with HIV, or if PrEP is initiated during undiagnosed acute infection. Here we use a macaque model of SHIV infection to model risks of drug resistance to CAB-LA PrEP.

Progestin-based contraception regimens modulate expression of putative HIV risk factors in the vaginal epithelium of pig-tailed Macaques.

Problem: In women, the use of progestin-based contraception may increase the risk of vaginal HIV acquisition. We previously showed in macaques that there is a significantly higher simian-human immunodeficiency virus (SHIV) acquisition rate in the luteal phase of the menstrual cycle, which presents a naturally high-progesterone state, and this may be attributable to altered expression of innate immune factors. We hypothesized that progestin-based contraception, especially depot medroxyprogesterone acetate (DMPA), would, in a similar way, affect mucosal immune factors that influence HIV acquisition risk.

Development of a repeat-exposure penile SHIV infection model in macaques to evaluate biomedical preventions against HIV.

Penile acquisition of HIV infection contributes substantially to the global epidemic. Our goal was to establish a preclinical macaque model of penile HIV infection for evaluating the efficacy of new HIV prevention modalities. Rhesus macaques were challenged once or twice weekly with consistent doses of SHIVsf162P3 (a chimeric simian-human immunodeficiency virus containing HIV env) ranging from 4-600 TCID50 (50% tissue culture infective dose), via two penile routes, until systemic SHIV infection was confirmed.

Novel multipurpose pod-intravaginal ring for the prevention of HIV, HSV, and unintended pregnancy: Pharmacokinetic evaluation in a macaque model.

Globally, women bear an uneven burden for sexual HIV acquisition. Results from two clinical trials evaluating intravaginal rings (IVRs) delivering the antiretroviral agent dapivirine have shown that protection from HIV infection can be achieved with this modality, but high adherence is essential. Multipurpose prevention technologies (MPTs) can potentially increase product adherence by offering protection against multiple vaginally transmitted infections and unintended pregnancy.

Development of a rectal sexually transmitted infection (STI) Model in Rhesus macaques using Chlamydia trachomatis serovars E and L.

Background: Rectal STI coinfection models enhance the understanding of rectal HIV transmission risk factors.

Materials And Methods: Rhesus macaques (n=9) were exposed to one of three rectal Chlamydia trachomatis (CT) challenges: C. trachomatis L (CT-L ); C.

A Depot Medroxyprogesterone Acetate Dose That Models Human Use and Its Effect on Vaginal SHIV Acquisition Risk.

Introduction: Hormonal contraception with depot medroxyprogesterone acetate (DMPA) may increase HIV acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. In this study, we test the impact of a low DMPA dose, designed to resemble human contraceptive use, on Simian-Human Immunodeficiency Virus (SHIV) acquisition risk in pigtail macaques (Macaca nemestrina).

Methods: Macaques metabolize DMPA faster than humans.

Combination Emtricitabine and Tenofovir Disoproxil Fumarate Prevents Vaginal Simian/Human Immunodeficiency Virus Infection in Macaques Harboring Chlamydia trachomatis and Trichomonas vaginalis.

Genital inflammation associated with sexually transmitted infections increases susceptibility to human immunodeficiency virus (HIV), but it is unclear whether the increased risk can reduce the efficacy of pre-exposure prophylaxis (PrEP). We investigated whether coinfection of macaques with Chlamydia trachomatis and Trichomonas vaginalis decreases the prophylactic efficacy of oral emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). Macaques were exposed to simian/human immunodeficiency virus (SHIV) vaginally each week for up to 16 weeks and received placebo or FTC/TDF pericoitally.

Relationship of Estimated SHIV Acquisition Time Points During the Menstrual Cycle and Thinning of Vaginal Epithelial Layers in Pigtail Macaques.

Background: HIV acquisition in the female genital tract remains incompletely understood. Quantitative data on biological HIV risk factors, the influence of reproductive hormones, and infection risk are lacking. We evaluated vaginal epithelial thickness during the menstrual cycle in pigtail macaques (Macaca nemestrina).

Analysis of putative mucosal SHIV susceptibility factors during repeated DMPA treatments in pigtail macaques.

Background: Depot-medroxyprogesterone acetate (DMPA) has been associated in some studies with increased HIV susceptibility in women. We used a pigtail macaque model to document the effects of repeated DMPA treatments and their potential contribution to increased SHIV susceptibility.

Methods: Nine pigtails were administered 2.

Depot-medroxyprogesterone acetate does not reduce the prophylactic efficacy of emtricitabine and tenofovir disoproxil fumarate in macaques.

Concerns that the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) may increase the risk of HIV acquisition in women led to questions on whether DMPA could reduce efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention. We used a macaque model to investigate the impact of prolonged DMPA exposure on PrEP with emtricitabine/tenofovir disoproxil fumarate. Twelve pigtail macaques treated with DMPA were exposed vaginally to simian HIV once a week for up to 5 months and received either placebo (n = 6) or emtricitabine/tenofovir disoproxil fumarate (n = 6).

Physiologic doses of depot-medroxyprogesterone acetate do not increase acute plasma simian HIV viremia or mucosal virus shedding in pigtail macaques.

Objective: Epidemiologic studies remain inconclusive on whether the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) increases mucosal HIV shedding and transmissibility. Nonhuman primate models may help to determine the effects of DMPA on acute HIV replication.

Design: We defined a physiologic dose of DMPA in macaques and assessed the impact of DMPA on acute simian HIV (SHIV) replication.

Increased susceptibility to vaginal simian/human immunodeficiency virus transmission in pig-tailed macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis.

Background: Sexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) infection, but their biological effect on HIV susceptibility is not fully understood.

Methods: Female pig-tailed macaques inoculated with Chlamydia trachomatis and Trichomonas vaginalis (n = 9) or medium (controls; n = 7) were repeatedly challenged intravaginally with SHIVSF162p3. Virus levels were evaluated by real-time polymerase chain reaction, plasma and genital cytokine levels by Luminex assays, and STI clinical signs by colposcopy.

Development of a rectal sexually transmitted infection--HIV coinfection model utilizing Chlamydia trachomatis and SHIVSF162p3.

Background: Rectal sexually transmitted infections (STIs) may increase HIV susceptibility in men who have sex with men (MSM), and Chlamydia trachomatis is prevalent among HIV-positive MSM. To study STIs and HIV infection in MSM, we first evaluated whether cynomolgus macaques can sustain both C. trachomatis and SHIVSF162p3 infections.