Dataset Information

Antibodies for HIV prevention in young women.

ABSTRACT: Young women in sub-Saharan Africa bear a disproportionate HIV burden. They urgently require new HIV prevention approaches that they can use. This review provides an overview of the use of antiretrovirals for HIV preexposure prophylaxis (PrEP), highlighting some of the challenges with this technology and explores the potential role of mAbs for HIV prevention in women.Recent findings on the initial steps in viral entry and establishment of a productive local infectious nidus in the vaginal epithelium has provided important clues for HIV prevention in the female genital tract. Topical and oral formulations of antiretroviral drugs have been shown to prevent HIV infection in women with varying levels of success, depending principally on adherence. Further, several new broad and potent mAbs have been isolated over the last 5 years. Nonhuman primate studies demonstrate that broadly neutralizing HIV mAbs can protect rhesus macaques from simian immunodeficiency virus-HIV chimera (SHIV) infection. These findings have created newfound enthusiasm for passive immunization as a potential prevention strategy for women.If potent broadly neutralizing mAbs are effective in preventing HIV infection in women, this outcome could fill an important gap in HIV prevention technologies for young women, especially in Africa.

SUBMITTER: Abdool Karim SS

PROVIDER: S-EPMC4771868 | biostudies-other | 2015 May

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Antibodies for HIV prevention in young women.

Abdool Karim Salim S SS Abdool Karim Quarraisha Q Baxter Cheryl C

Current opinion in HIV and AIDS 20150501 3

<h4>Purpose of review</h4>Young women in sub-Saharan Africa bear a disproportionate HIV burden. They urgently require new HIV prevention approaches that they can use. This review provides an overview of the use of antiretrovirals for HIV preexposure prophylaxis (PrEP), highlighting some of the challenges with this technology and explores the potential role of mAbs for HIV prevention in women.<h4>Recent findings</h4>Recent findings on the initial steps in viral entry and establishment of a produc ...[more]

PMID: 25700207

Similar Datasets

Project description:IntroductionThe last 12 years have seen remarkable progress in the isolation and characterization of at least five different epitope classes of HIV-specific broadly neutralizing antibodies (bnAbs). Detailed analyses of these bnAb lineages, maturation pathways and epitopes have created new opportunities for vaccine development. In addition, interest exists in passive administration of monoclonal antibodies as a viable option for HIV prevention.DiscussionRecently, two antibody-mediated prevention (AMP) trials of a passively administered monoclonal antibody targeting the HIV envelope CD4 binding site, called VRC01, provided proof-of-concept that monoclonal antibody infusion could offer protection against HIV acquisition. While the trials failed to show overall protection against HIV acquisition, sub-analyses revealed that VRC01 infusion provided a 75% prevention efficacy against HIV strains that were susceptible to the antibody. The study also demonstrated that in vitro neutralizing activity, measured by the TZM-bl/pseudovirus assay, was able to predict HIV prevention efficacy in humans. In addition, the AMP trials defined a threshold protective concentration, or neutralization titer, for the VRC01 class of bnAbs, explaining the observed low overall efficacy and serving as a benchmark for the clinical testing of new bnAbs, bnAb cocktails and neutralizing antibody-inducing vaccines. Newer bnAbs that exhibit greater potency and breadth of neutralization in vitro than VRC01 are available for clinical testing. Combinations of best-in-class bnAbs with complementary magnitude, breadth and extent of complete neutralization are predicted to far exceed the prevention efficacy of VRC01. Some engineered bi- and trispecific mAbs exhibit similar desirable neutralizing activity and afford advantages for manufacturing and delivery. Modifications that prolong the serum half-life and improve genital tissue persistence offer additional advantages.ConclusionsIterative phase 1 trials are acquiring safety and pharmacokinetic data on dual and triple bnAbs and bi- and trispecific antibodies in preparation for future AMP studies that seek to translate findings from the VRC01 efficacy trials and achieve acceptable levels of overall prevention efficacy.

Project description:Preventing new HIV infections, especially amongst young women, is key to ending the HIV epidemic especially in sub-Saharan Africa. Potent antiretroviral (ARV) drugs used as pre-exposure prophylaxis (PrEP) are currently being formulated as long-acting implantable devices, or nanosuspension injectables that release drug at a sustained rate providing protection from acquiring HIV. PrEP as implants (PrEP Implants) offers an innovative and novel approach, expanding the HIV prevention toolbox. Feedback from providers and future users in the early clinical product development stages may identify modifiable characteristics which can improve acceptability and uptake of new technologies. Healthcare workers (HCWs) perspectives and lessons learned during the rollout of contraceptive implants will allow us to understand what factors may impact the roll-out of PrEP implants. We conducted eighteen interviews with HCWs (9 Nurses and 9 Community Healthcare Workers) in rural KwaZulu-Natal, South Africa. HCWs listed the long-acting nature of the contraceptive implant as a key benefit, helping to overcome healthcare system barriers like heavy workloads and understaffing. However, challenges like side effects, migration of the implant, stakeholder buy-in and inconsistent training on insertion and removal hampered the roll-out of the contraceptive implant. For PrEP implants, HCWs preferred long-acting products that were palpable and biodegradable. Our findings highlighted that the characteristics of PrEP implants that are perceived to be beneficial by HCWs may not align with that of potential users, potentially impacting the acceptability and uptake of PrEP implants. Further our data highlight the need for sustained and multi-pronged approaches to training HCWs and introducing new health technologies into communities. Finding a balance between the needs of HCWs that accommodate their heavy workloads, limited resources at points of delivery of care and the needs and preferences of potential users need to be carefully considered in the development of PrEP implants.

Project description:IntroductionIn 2018, the National AIDS and sexually transmitted infection (STI) Control Programme developed a national guidelines to facilitate the inclusion of young women who sell sex (YWSS) in the HIV prevention response in Kenya. Following that, a 1-year pilot intervention, where a package of structural, behavioural and biomedical services was provided to 1376 cisgender YWSS to address their HIV-related risk and vulnerability, was implemented.MethodsThrough a mixed-methods, pre/post study design, we assessed the effectiveness of the pilot, and elucidated implementation lessons learnt. The three data sources used included: (1) monthly routine programme monitoring data collected between October 2019 and September 2020 to assess the reach and coverage; (2) two polling booth surveys, conducted before and after implementation, to determine the effectiveness; and (3) focus group discussions and key informant interviews conducted before and after intervention to assess the feasibility of the intervention. Descriptive analysis was performed to produce proportions and comparative statistics.ResultsDuring the intervention, 1376 YWSS were registered in the programme, 28% were below 19 years of age and 88% of the registered YWSS were active in the last month of intervention. In the survey, respondents reported increases in HIV-related knowledge (61.7% vs. 90%, p <0.001), ever usage of pre-exposure prophylaxis (8.5% vs. 32.2%, p < 0.001); current usage of pre-exposure prophylaxis (5.3% vs. 21.1%, p<0.002); ever testing for HIV (87.2% vs. 95.6%, p <0.04) and any clinic visit (35.1 vs. 61.1, p <0.001). However, increase in harassment by family (11.7% vs. 23.3%, p<0.04) and discrimination at educational institutions (5.3% vs. 14.4%, p<0.04) was also reported. In qualitative assessment, respondents reported early signs of success, and identified missed opportunities and made recommendations for scale-up.ConclusionsOur intervention successfully rolled out HIV prevention services for YWSS in Mombasa, Kenya, and demonstrated that programming for YWSS is feasible and can effectively be done through YWSS peer-led combination prevention approaches. However, while reported uptake of treatment and prevention services increased, there was also an increase in reported harassment and discrimination requiring further attention. Lessons learnt from the pilot intervention can inform replication and scale-up of such interventions in Kenya.

Dataset Information

Antibodies for HIV prevention in young women.

Publications

Antibodies for HIV prevention in young women.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets