Conflict of Interest No conflicts of interest to declare.

Evaluation of memory CD8+ T cell responses in individuals initiating cART during hyperacute HIV-1 infection Thandeka Nkosi HIV Pathogenesis Programme Nelson R Mandela School of Medicine University of KwaZulu-Natal Durban, South Africa

KwaZulu-Natal and Durban, South Africa Gauteng Northern Province Mpumalanga North West Free State KwaZulu Natal Northern Cape Durban Eastern Cape Western Cape

HIV-1 incidence in 18-35 year old women in this community 9.1% HIV in pregnant women in rural South Africa (2001-2013) HIV-1 incidence in 18-35 year old women in this community 9.1% Age Group (Years) HIV Prevalence (N=4818) ≤16 11.5% 17-18 21.3% 19-20 30.4% 21-22 39.4% 23-24 49.5% >25 51.9% Source: Abdool Karim Q, 2014

FRESH (Females Rising through Education, Support and Health) Subjects: Uninfected 18-23 year old women at high risk of HIV infection Methods: Provide a twice weekly empowerment, life skills, job readiness and HIV prevention education curriculum with the goal of preventing HIV infections and placing all women in employment after one year Test twice weekly for HIV RNA by finger prick, with the goal of identifying hyperacute infections Test and treat

Acute infections detected (N = 56) As of June 17, 2017: 14 untreated, 79% Fiebig I 42 treated early, 84.2% Fiebig I Incidence 8.5 (95% CI=5.8-12.0) per 100 p/y

Typical treated and untreated acute HIV-1 infection Treatment: TDF/FTC/EFZ

Early ART blunts peak viremia in Fiebig I treated patients

Impact of early ART on CD8+ T cell responses Investigate if very early ART suppresses development of immune responses OR Early ART initiation, help to preserve CD8+ T cell immune responses

Persistent HIV-specific CD8+ T cell response following early cART initiation Tetramer CD8

Some patients started on cART in Fiebig I do not make detectable HIV-specific tetramer CD8+ T cell responses P2 Tetramer CD8

Some patients started on cART in Fiebig I do not have proliferative responses CFSE CD8

Majority of Fiebig I treated subjects make detectable HIV-specific CD8+T cell responses Assays used: Tetramer staining ELISPOT Assay CFSE Proliferation Assay

Increased CD127 expression on CD8+ T cells during early treated hyperacute HIV infection

HIV-specific CD8+ T cells in early treated subjects are more functionally competent Untreated IFN-gamma CD8 Tetramer

Conclusions Hyperacute infection can be identified at the center of the HIV epidemic in Durban, South Africa A large proportion of individuals treated in Fiebig I have detectable anti-HIV immune responses Understanding of immune responses in early treated people may be useful for future intervention studies

Acknowledgements Dr Zaza Ndhlovu Prof Thumbi Ndung’u Prof Bruce Walker Nikoshia Shen Karyn Pretorious Funsho Ogunshola Faatima Laher Omolara Baiyegunhi Nasreen Ismail HPP staff and students Study Participants