Newsletter October 2019 Volume18 Issue 10 Majority of the replication-competent HIV-1 reservoir is established close to In this Issue the time of treatment initiation collaboration between UCT, UNC tervals and compared to sequences of Our feature article this month fo- and CAPRISA researchers has viruses in the cellular reservoir after a cuses on the study published in uncovered that the HIV-1 latent viral outgrowth assay. Science Translational Medicine on A reservoir does not necessarily form con- HIV-1 latent reservoirs. tinuously as previously thought, but ra- For each outgrowth virus, the most ther that most latent viruses in individuals closely related variant in the blood pre- On page 2 we congratulate Prof on long-term antiretroviral therapy (ART) treatment was determined using genetic Quarraisha Abdool Karim who will are genetically most similar to those cir- distance and placement probability meth- receive an honorary degree from culating in the blood shortly before thera- ods. the University of Stellenbosch; and py initiation. scientists Drs Anushka Naidoo and The analysis revealed that ~71% of Navisha Dookie as recipients of a The study in nine women from the the replication-competent reservoir con- grant and a fellowship from the CAPRISA 002 cohort, published this sists of viruses that are genetically most NIH Fogarty’s Emerging Global month in Science Translational Medicine, similar to strains circulating in the blood Leader award and an EDCTP Fel- made use of phylogenetic analyses of within a year of ART initiation (Figure 1). lowship, respectively. next-generation sequencing data to in- dentify the timing of the establishment of Furthermore, these findings indicate a On page 3 we report on CA- the reservoir. The reservoir is the source rapid turnover in latently infected cells PRISA’s participation at the Grand of ongoing viral replication if patients stop over the course of untreated infection. Challenges Annual Meeting in Ad- ART and it represents the greatest chal- This led the authors to hypothesise that dis Ababa Ethiopia; PhD student, lenge to a cure for HIV. ART indirectly creates an environment in David Sack’s research on bNabs; which actively infected cells transition to and Dr Lenine Liebenberg’s partici- On average, the 9 women were treat- a resting state, potentially due to lack of pation in CoMA. ment naïve for 4.5 years and on ART for antigen stimulus. 4.9 years. Viruses were sequenced from We congratulate NICD Msc stu- the blood pre-treatment at 6-monthly in- This points to a window of opportunity dent who won the prize for the best to clear actively infected cells and/or pre- 3 minute presentation at the 14th vent their transition to a latent state at the H3Africa on page 4. time of initiating therapy. Melissa-Rose Abrahams CONTACT DETAILS For further reading see: Abrahams MR, et al. The replication-competent HIV CAPRISA -1 latent reservoir is primarily established near the Doris Duke Medical time of therapy initiation. Science Translational Research Institute (DDMRI) Medicine 2019 October; 11(513): eaaw5589. doi: 2nd Floor 10.1126/scitranslmed.aaw5589. https:// University of KwaZulu-Natal stm.sciencemag.org/content/11/513/ Private Bag X7, Congella 4013 South Africa T: +27-31-260 4555 Figure 1. Maximum-likelihood-like phylogenetic tree of the F: +27-31-260 4566 c2 to c3 region of the viral env gene of CAP257 and E-mail: [email protected] CAP288. Pre-ART sequences are in red (within the first www.caprisa.org.za year after transmission) to blue (within the year before ART), and reservoir outgrowth viruses are in pink. Weeks Caprisaofficial pre-ART are indicated alongside the colour key. @CAPRISAofficial October2019; 18(10): page 2 Professor Quarraisha Abdool Karim honoured for her pivotal role in HIV prevention research tellenbosch University (SU) will honorary doctorates are a way of confer an honorary doctorate acknowledging the remarkable work S on Professor Quarraisha of individuals who are regarded as Abdool Karim, for her ‘commitment to role models and an inspiration to research and education in the field of Stellenbosch graduates. Their con- women's health in Africa and globally, tributions to society through educa- particularly her successful efforts in tion, activism and research also increasing the national and interna- embody the values underpinning tional focus on HIV, and her pivotal role in HIV prevention research’. SU's Vision 2040 – compassion, respect, excellence, accountability The press statement released by and equity. Professor Abdool Kari- Stellenbosch University announcing m’s honorary doctorate will be the conferral of the 2019/2020 honor- conferred during SU’s March/April ary degrees stated: ‘The university’s 2020 graduation ceremony. CAPRISA scientist receives Fogarty’s 2019 Emerging Global Leader Award e congratulate CA- porting the transition from an early stage to lead inves- PRISA Scientist, tigator. The research focus is in HIV-associated tuber- W Anushka Naidoo. culosis (TB) in South Africa. The World Health Organi- PhD, who is a recipient of the zation recommends the antiretroviral drug dolutegravir National Institutes of Health as first-line treatment of HIV, however, dolutegravir is (NIH) Fogarty’s 2019 Emerg- not recommended in patients with HIV-TB co-infection. ing Global Leader Award Tuberculosis drug interactions may reduce dolutegravir of $538,000 over five efficacy. years, aimed at establishing “This study aims to fill this knowledge gap by under- independent careers in glob- standing the impact of drug interactions with tuberculo- al health under the guidance sis drugs on dolutegravir drug concentrations, adher- of experienced mentors in ence and treatment outcomes, said Naidoo. the US and in developing The study will be conducted in a high HIV-TB bur- countries. den setting in KwaZulu-Natal South Africa. Naidoo’s proposal present- We wish Naidoo every success as she leaves her ed a five-year research career development program post in Pharmacy to embark on a career as an inde- focused on clinical pharmacology that included training pendent researcher. and mentorship and research activities aimed at sup- EDCTP Fellowship awarded to scientist APRISA congratulates Scientist Nav- search ownership in the region. Dookie was isha Dookie, PhD on being awarded awarded the funding of €140 000 over a 3- C an European and Developing Coun- year period. tries Clinical Trials Partnership (EDCTP) The overall aim of the fellowship said Career Development Award aimed at Dookie was to ‘optimise the clinical utility of providing individual training to talented whole genome sequencing for the detection early-career scientists to develop as inde- of drug-resistant tuberculosis’. pendent researchers and team leaders at She is being mentored by Prof Kogie host institutions in sub-Saharan Africa for Naidoo head of HIV-TB Treatment Re- long-term continuity, networking and re- search at CAPRISA. October 2019; 18(10): page 3 Building momentum for global Diverted Antibody health and development Evolution – implications for bnAbs recent study, published in PLoS Pathogens by NICD A PhD student David Sacks, shows how somatic hypermuta- tion to counter a globally rare viral sequence drove off-track antibodies in the CAP256- VRC26 bnAb lineage. bnAbs develop in only a few HIV infect- ed individuals. Their develop- ment is complicated by complex evolutionary (L-R) Peter Singer, senior advisor to the WHO Director-General with pathways that are characterized by extensive so- Jerome Singh and Salim Abdool Karim from CAPRISA matic hypermutation of antibodies. APRISA participated in the 2019 Grand Challenges Previous work by Jinal Bhiman showed that Annual Meeting co-hosted by Ethiopia’s Ministry of CAP256-VRC26 lineage includes both bnAbs and C Health, Grand Challenges Canada, the United highly mutated “off-track” lineage members that States Agency for International Development and the Bill & share high sequence identity to broad members but lack breadth. Melinda Gates Foundation, from 27 – 30 October held in Addis Ababa, Ethiopia. In this study, Sacks defined the specific muta- tions that limit breadth in two “off-track” members The primary aim of the meeting was to build momentum of the CAP256-VRC26 bNAb lineage, and for global health and development through innovation and showed that these occur with a relatively high scientific collaboration among international groups and probability. He also showed how a dominant virus researchers. The meeting convenes over 1,000 key lead- within the CAP256 donor, that had a globally rare ers from across the global community to share best prac- V2 sequence, selected for an off-track antibody, tices, encourage collaboration and seek solutions for com- providing a mechanism for the development of mon challenges. this antibody during infection. Professor Salim Abdool Karim, CAPRISA’s Director, These data show that affinity maturation to delivered a spotlight talk (akin to a TED talk) on the devel- counter globally rare viral immunotypes can drive opment of CAP256 bnAb for HIV prevention. antibodies within a broad lineage along multiple Professor Jerome Singh, head of Ethics and Law at pathways towards strain-specificity. Defining de- CAPRISA participated in a plenary session on science ad- velopmental pathways towards and away from vocacy and the official press conference to discuss gene breadth will facilitate the selection of immunogens drive - an approach to genetically modify mosquitoes for that elicit bnAbs and minimize off-track antibod- malaria control. ies. For further reading: Sacks D, et al. Somatic hypermutation He also participated as a panellist in a Q&A session to counter a globally rare viral immunotype drove off-track entitled: Innovation for Good, Innovation for Growth, held antibodies in the CAP256-VRC26 HIV-1 V2-directed bNAb in the United Nations Conference Center and the Coalition lineage. PLoS Pathogens. 2019;15(9):e1008005. doi: for African Research and Innovation (CARI) Pharma Work- 10.1371/journal.ppat.1008005. https:// ing Group meeting.