Track A Report: Biology and Pathogenesis of HIV H. Engers (8 December 2011) Own, Scale-up & Sustain

Track A Rapporteurs Lead Rapporteur: Howard Engers (Switzerland): Rapporteur team: 1) Alain Azondekon (Benin) 2) Markos Abebe (Ethiopia) 3) Ebba Abate (Ethiopia) 4) Workinesh Ayele (Ethiopia)

Track A Team

Track A Themes HIV infection and replication, transmission, genetics, evolution; HIV structure and function, and pathogenesis; Adaptive and innate immune responses to HIV; Genetic susceptibility to HIV; Interaction of micronutrients; Co-infections and progress in animal models; Discussions related to pre-clinical vaccine, microbicide and drug development (over 85 presentations/abstracts)

Monitoring of the Viral status of African patients (EHNRI) Many challenges/issues related to the rapid and extensive roll-out of ARV treatments in Africa (estimated that over 350,000 patients will require ART in 2011 In Ethiopia) Ethiopia

Monitoring of the Viral status of African patients Two studies demonstrated a reduced cost and/or time for assay execution: - Ethiopia - strategy of 10x10 matrix pooling (Gebru) single assay = 647 Birr (13days) matrix assay = 190 Birr (4 days) - USA/Nigeria - ligation amplification PCR method, (Ulenga) ViroSeq = 200 US$ per test Lig Amp = 20 US$ per test (aiming at 6 US$)

Monitoring of the Viral status of African patients Several studies reported novel approaches to monitor viral status; Reduced cost, reduced assay times and applicability at point of care were stressed; Technical issues: - certain reagents require a cold chain - avoid frequent freezing and thawing of serum samples - procurement of reagents under African context - quality management & validation of in-house assays

Vision: The African Society for Laboratory Medicine envisions all African nations providing affordable access to quality laboratory services, which make possible effective treatment and prevention of disease and a better life for all persons web:

Monitoring of the Immunological status of HIV patients Afework Kassu Gizaw and ǂ Brent Palmer ǂ Allergy and Clinical Immunology, University of Colorado Denver, USA example: Dysfunction of HIV-specific CD4+ T cells During Chronic HIV Infection is Associated with Elevated Concurrent Expression of Multiple Inhibitory Receptors

Co-regulation of T cell function in HIV infected individuals CD4+ Helper T cell CD4+ Helper T cell Co- Stimulatory Co-Inhibitory TCR complex Proliferate Produce effector cytokines (IFN- , TNF-  ) Positive signal Negative signal Produce helper cytokines (IL-2) (Kassu) antigen

Conclusions on T cell Function Co-expression of the three inhibitory receptors on HIV-specific CD4 + T cells correlates more strongly with HIV viral load than expression of each individually. - regulation of HIV specific CD4 + T cell response during chronic HIV infection by complex patterns of co-expressed inhibitory receptors, suggesting the ability of HIV to exploit negative regulatory pathways to facilitate its persistence. In vitro blockade of the PD-1/PD-L1 pathway concurrent with stimulation through CD28 synergistically increases HIV-specific CD4 + T cell proliferation - suggests that targeting both inhibitory and stimulatory pathways is better than PD-1 receptor blockade alone. (Kassu)

Chiodi, Journal of Clinical Investigation 2010 Two phase-model for depletion of memory B cells from circulation Altered migration Apoptosis

Correlates of protection…… Pensieroso S and Nilsson A et al. PNAS Modified strategies for childhood immunisation are needed in HIV-1 infected children

Many unresolved questions regarding initiation and maintenance of humoral immunity in children Improved vaccination outcome in the HIV-1 infected child is needed to decrease morbidity and mortality from vaccine–preventable diseases (measles, IPD, rotavirus) New vaccines coming into practice should be evaluated in Africa, both in healthy and immuno- compromised children Summary and future perspectives for childhood immunisation (Anna Nilsson, Karolinska Institutet)

HIV Vaccines for Africa Vaccines remain a very desirable (perhaps essential?) HIV control tool to add to the current interventions used in Africa HIV vaccines remain elusive and will require many more years of hard work, (basic and clinical) research and clinical testing in Africa Collaboration, partnerships and networking will be essential for success ( see the new for more details)

RV144 Trial- Renewed hope (Pontiano)

Move the RV144 The Pox-Protein Public Private Partnership (P5) Sanofi, Novartis, NIH, HVTN, DoD, to move RV144 vaccine to a potentially licensable one –Trials planned in Southern Africa (Pontiano)

HIV Prevention trials in Africa in randomized HIV/AIDS prevention or treatment intervention trials in North America 80 were conducted in Africa 20% were led by an African (Souleymane Mboup) Own, Scale-up & Sustain

Barriers to conduct of international level HIV Prevention trials in SSA Lack of adequate and sustainable research funding Lack of a critical mass of well trained researchers Lack of adequate research infrastructure Lack of enabling environment for research (e.g. poor ethics and regulatory standards) Isolation of well trained cadres Lack of sharing of facilities and expertise Lack of mapping and synergising efforts Lack of common advocacy Invisible role of public sector (Souleymane Mboup)

How do we Own, Scale-up & Sustain Basic Science research in Africa ?? Increase the priority for quality biomedical research in Africa – universities, research institutes, etc. Implement/support capacity building programmes which produce imaginative, motivated African researchers Attract and retain quality African researchers Establish and maintain relevant partnerships and networks, South-North and South-South Tap into the vast supply of potential African mentors and collaborators working abroad

Thank you Amesegenalehu