Ravi Gupta's research career is focused on emergence of global HIV drug resistance. Having completed his specialist medical training in infectious diseases and a Masters in International Public Health, he now works on clinical/epidemiological aspects of drug resistance as well as in vitro investigation of susceptibility to protease inhibitors, a major class of drugs now being widely used to tackle first line treatment failure globally. His doctoral work also included work on mammalian innate immune restriction factors, generating interest in innate immune cells such as macrophages. The lab now also works on how HIV parasitises long lived macrophages and the role of these cells as a reservoir of HIV, including drug resistant strains.
In addition we are studying the underlying virus and host biology behind HIV 'elite controllers' who are able to naturally control infection without drug therapy. Such insights may lead to alternative treatments for HIV.
The Gupta lab has teams in both the UK and at the Africa Health Research Institute in Durban South Africa. Our work focuses on two areas:
- Studying HIV drug resistance to protease / integrase inhibitors and implications for global scale up of antiretroviral therapy.
- Dissecting the biology of macrophage-virus interactions given myeloid cells are parasitised by HIV and are a difficult-to-treat reservoir.Ravi Gupta has been Professor of Clinical Microbiology at the Cambridge Institute for Therapeutic Immunology and Infectious Diseases since 2019. His group has recently introduced the SAMBA II point of care test into clinical practice at Addenbrookes for rapid diagnosis of COVID19. During the pandemic the lab has also started a basic science program to understand firstly the antiviral activity of drugs like lopinavir, azithromyin and chloroquine, but also to understand the basis of the second immune mediated part of the disease process that likely involves macrophages.
Ravi Gupta has been Professor of Clinical Microbiology at the Cambridge Institute for Therapeutic Immunology and Infectious Diseases since 2019.
COVID19 related work
His group has recently introduced the SAMBA II point of care test into clinical practice at Addenbrookes for rapid diagnosis of COVID19. During the pandemic the lab has also started a basic science program to understand firstly the antiviral activity of drugs like lopinavir, azithromyin and chloroquine, but also to understand the basis of the second immune mediated part of the disease process that likely involves macrophages.
BBC interview on COVID-19 work, 2 April 2020 https://youtu.be/Jn5rVCa00ng
HIV-1 Remission in London patient. The Gupta lab's collaborative work is published in Nature and reported around the world: HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Gupta RK, Abdul-Jawad S, McCoy LE, Mok HP, Peppa D, Salgado M, Martinez-Picado J, Nijhuis M, Wensing AMJ, Lee H, Grant P, Nastouli E, Lambert J, Pace M, Salasc F, Monit C, Innes A, Muir L, Waters L, Frater J, Lever AML, Edwards SG, Gabriel IH, Olavarria E. Nature. 2019 Mar 5. doi: 10.1038/s41586-019-1027-4. [Epub ahead of print]
Prof Gupta presented the work at CROI
Below are key publications from the Gupta lab.
Mlcochova P, Winstone H, Zuliani-Alvarez L, Gupta RK. TLR4-Mediated Pathway Triggers Interferon-Independent G0 Arrest and Antiviral SAMHD1 Activity in Macrophages. Cell Reports 2020; 30 (12), 3972-3980
Ravindra K. Gupta, Dimitra Peppa, Alison L Hill Cristina Gálvez Maria Salgado5Matthew Pace, Laura E McCoySarah A Griffith, John Thornhill, Aljawharah Alrubayyi, Laura EP Huyveneers, Eleni Nastouli, Paul Grant, Simon G Edwards S , Andrew J Innes, John Frater, Monique Nijhuis, Anne Marie J, Wensing Prof Martinez-Picado J, Eduardo Olavarria. Evidence for HIV-1 Cure in the ‘London Patient’. The Lancet HIV 2020; S2352-3018(20)30069-2.
El Bouzidi K, Kemp SA, Datir RP, Murtala-Ibrahim F, Aliyu A, Kwaghe V, Frampton D, Roy S, Breuer J, Sabin CA, Ogbanufe O, Charurat ME, Bonsall D, Golubchik T, Fraser C, Dakum P, Ndembi N, Gupta RK. High prevalence of the integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment. J Antimicrob Chemother. 2020 Feb 27. pii: dkaa033. doi: 10.1093/jac/dkaa033
Gupta RK, Abdul-Jawad S, McCoy LE, Mok HP, Peppa D, Salgado M, Martinez-Picado J, Nijhuis M, Wensing AMJ, Lee H, Grant P, Nastouli E, Lambert J, Pace M, Salasc F, Monit C, Innes A, Muir L, Waters L, Frater J, Lever AML, Edwards SG, Gabriel IH, Olavarria E. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature. 2019 Mar 5. doi: 10.1038/s41586-019-1027-4. [Epub ahead of print]
Derache A, Iwuji C, Danasivah S, Giandhari J, Marcelin AG, Calvez V, de Oliveira T, Dabis F, Pillay D, Gupta RK for the ANRS 12249 TasP Study Group. Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART. Journal of Antimicrobial Chemotherapy 2018
MlcochovaP, Caswell S, Taylor I, TowersGJ, Gupta RK. DNA damage induced by topoisomerase inhibitors activates SAMHD1 and blocks HIV-1 infection of macrophages. The EMBO J 2018; 37:50–62
Gupta RK, Gregson J, Parkin N, Haile-Selassie H, Tanuri A, Andrade Forero L, Kaleebu P , Watera C, Aghokeng A, Mutenda N, Dzangare J, Hone S, Hang ZZ, Garcia J, Garcia Z, Marchorro P, Beteta E, Roman M, Giron A, Hamers R, InzaukeS, Frenkel LM, Chung MH,de Oliveira T, Pillay D, Naidoo K, Kharsany A, Kugathasan R, Cutino T, Hunt G, Avila Rios S, Doherty M, Jordan MR, Bertagnolio S. HIV-1 drug resistance prior to initiation or re-initiation of first-line antiretroviral therapy in low- and middle-income countries – a meta regression analysis. Lancet Infectious Diseases 2018 Mar;18(3):346-355
Mlcochova P, Caswell S, Taylor I, Towers GJ, Gupta RK. Topoisomerase inhibitors activate SAMHD1 and block HIV-1 infection in macrophages, EMBO J. 2018 Jan 4;37(1):50-62.
Collier DA, Iwuji C, Derache A, de Oliveira T, Okesola N, Calmy A, Dabis F, Pillay D, Gupta RK for the ANRS 12249 TasP Study Group. Virological Outcomes of second– line protease inhibitor based treatment for HIV– 1 in a high prevalence rural South African setting – a competing risk prospective cohort analysis. Clin Infect Dis. 2017 Apr 15;64(8):1006-1016
Petra Mlcochova, Katherine A Sutherland, Sarah A Watters, Cosetta Bertoli, Rob AM de Bruin, Jan Rehwinkel, Stuart J Neil, Gina M Lenzi, Baek Kim, Asim Khwaja, Matthew C Gage, Christiana Georgiou, Alexandra Chittka, Simon Yona, Mahdad Noursadeghi, Greg J Towers, Ravindra K Gupta. A G1‐like state allows HIV‐1 to bypass SAMHD1 restriction in macrophages. The EMBO Journal (2017) e201696025. Published online 25.01.2017
Rhee S, VargheseV, HolmesSP, Van ZylGU, SteegenK, BoydMA, CooperDA, NsanzimanaS, SaravananS, CharpentierC, de OliveiraT, EtiebetMAA, GarciaF, GoedhalsD, GomesP, GünthardHF, HamersRL, HoffmannCJ, HuntG, JiamsakulA, KaleebuP, KankiPJ, Kantor R, KerschbergerB, Marconi VC, Jd’Amour NdahimanaJ, NdembiN, Ngo-Giang-HuongN, RokxC, SantoroMM, SchapiroJM, SchmidtD, SeuL, SigaloffKCE, SirivichayakulS, SkhosanaL, SunpathH, TangM, Yang C, Carmona S, Gupta RK*, Shafer RW* (co-senior author).Mutational correlates of virological failure in individuals receiving a WHO-recommended tenofovir-containing first-line regimen: an international collaboration. EbioMedicine 2017 Apr;18:225-235.
Kugathasan R, Collier DA, Haddow LJ, El Bouzidi K, Edwards SG, Cartledge JD, Miller RF, Gupta RK. Diffuse white matter signal abnormalities on MRI are associated with HIV-1 viral escape in the central nervous system among patients with neurological symptoms. Clin Infect Dis. 2017 Apr 15;64(8):1059-106
Goodall R, Dunn DT, Nkurunziza P, Mugarura L, Pattery T, Munderi P, Kityo C, Gilks C, Kaleebu P, Pillay D, Gupta RK on behalf of the DART Virology Group. Rapid accumulation of HIV-1 thymidine analogue mutations and phenotypic impact following prolonged viral failure on zidovudine based first line antiretroviral therapy in sub Saharan Africa. J Antimicrob Chemother. 2017 May 1;72(5):1450-1455
Sutherland KA, Collier DA, Claiborne DT, Prince JL, Deymier MJ, Goldstein RA, Hunter E, Gupta RK. Wide variation in susceptibility of HIV-1 subtype C Isolates to protease inhibitors and association with in vitro replication efficiency. Scientific Reports 2016; 6: 38153 doi: 10.1038/srep38153
Gregson J, Kaleebu P, Marconi VC, van Vuuren C, Ndembi N, Hamers RL, Kanki P, Hoffmann CJ, Lockman S, Pillay D, de Oliveira T, Clumeck N, Hunt G, Kerschberger B, Shafer RW, Yang C, Raizes E, Kantor R, Gupta RK. Occult drug resistance to thymidine analogues and multidrug resistant HIV-1 following failure of first line tenofovir-based antiretroviral regimens in sub Saharan Africa: a retrospective multi-centre cohort study. Lancet Infect Dis 2016, Volume 17, No. 3, p296–304, March 2017
Watters SA, Mlcochova P, Maldarelli F, Goonetilleke N Pillay D Gupta RK. Sequential CCR5-Tropic HIV-1 Reactivation From Distinct Cellular Reservoirs Following Perturbation of Elite Control. PLoS One. 2016 Jul 12;11(7):e0158854
El Bouzidi K, Collier Dami, Nastouli E, Copas A, Miller RF, Gupta RK. Virologic Efficacy of Protease Inhibitor Monotherapy for HIV-1 in Clinical Practice. J Antimicrob Chemother. 2016 Nov;71(11):3228-3234. Epub 2016 Jul 7.
Gregson J, Tang M, Ndembi N, Hamers RL, Rhee SY, Marconi VC, Diero L, Brooks K, Theys, K, Rinke de Wit TF, Arruda M, Garcia F, Monge S, Günthard, HF, Hoffmann, CJ, Kanki PJ, Kumarasamy, N, Kerschberger B, Mor O, Charpentier C, Todesco E, Rokx C, Gras L, Halvas EK, Sunpath H, Di Carlo D, Antinori A, Andreoni M, Latini A, Mussini C, Aghokeng A, Sonnerborg A, Ujjwal Neogi U, Fessel WJ, Agolory S, Yang C, Blanco JL, Juma JM, Smit, E, Schmidt, D, Watera C, Asio J, Kirungi W, Tostevin A, El-Hay T, Clumeck N, Goedhals D; van Vuuren C, Bester PA, Sabin C, Mukui I, Santoro MM, Perno CF, Hunt G, Morris L, Camacho R, de Oliveira T, Pillay D, Schulter E, Akio Murakami-Ogasawara A, Reyes-Terán G, Romero K, Avila-Rios S, Sirivichayakul, S, Ruxrungtham K, Mekprasan S, Dunn, D, Kaleebu, P, Raizes E, Kantor R, Shafer RW, Gupta RK on behalf of the TenoRes study group. Global epidemiology of drug resistance following failure of WHO recommended first line regimens for adult HIV-1 infection – a multi-centre retrospective cohort study. Lancet Infect Dis Volume 16, No. 5, p565–575, May 2016
Sutherland KA, Goodall RL, McCormick A, Kapaata A, Lyagoba F, Kaleebu P, Thiltgen G, Gilks C, Spyer M, Kityo C, Pillay D, Dunn D, Gupta RK, on behalf of the DART Virology Group and DART Trial Team. Gag-Protease sequence evolution following protease inhibitor monotherapy treatment failure in HIV-1 viruses circulating in East Africa. AIDS Research and Human Retroviruses. 2015. Oct; 31(10):1032-7. doi: 10.1089/aid.2015.0138. Epub 2015 Aug 10. PubMed PMID: 26258548
Sutherland KA, Parry CM, McCormick A, Kapaata A, Lyagoba F, Kaleebu P, Gilks C, Goodall RL, Spyer M, Kityo C, Pillay D, Gupta RK, on behalf of the DART Virology Group. Evidence for reduced drug susceptibility without emergence of major protease mutations following protease inhibitor monotherapy failure in the SARA trial. PLoS One 2015, 2015 Sep 18;10(9):e0137834
Lange CM, Hué S, Violari A, Cotton MF, Gibb D, Babiker A, Abdel G, Otwombe K, Panchia R, Jean-Philippe P, McIntyre JA, Pillay D & Gupta RK. Single genome analysis for detecting multi-class drug resistance in HIV-1 infected children on protease inhibitor-based first line therapy. J Acquir Immune Defic Syndr. 2015 Mar 6.
Smith NMG, Mlcochova P, Watters SA, Aasa-Chapman, Rabin N, Moore S, Edwards SG, Garson JA, Grant PR, Ferns RB, Kashuba A, Mayor NP, Schellekens J, Marsh SGE, McMichael AJ, Perelson AS, Pillay D, Goonetilleke N, Gupta RK. Proof-of-principle for immune control of global HIV-1 reactivation in vivo. Clin Infect Dis. 2015 Mar 16. pii: civ219.
Mlcochova P, ApoloniaL, Kluge SF, Sridharan A, Kirchhoff F, Malim MH, Sauter D, Gupta RK. Immune evasion activities of accessory proteins Vpu, Nef and Vif are conserved in acute and chronic HIV-1 infection. Virology. 2015 Aug;482:72-8.
Sutherland KA, Ghosn J , Gregson J, Mbisa JL , Chaix ML, Cohen Codar I, Delfraissy JF, Delaugerre C and Gupta RK. HIV-1 subtype influences susceptibility and response to monotherapy with the protease inhibitor lopinavir/ritonavir. Journal of Antimicrobial Chemotherapy 2015;70(1):243-8
Mlcochova P, Watters S, Towers GJ, Noursadeghi M, Gupta RK. Vpx complementation of 'non-macrophage tropic' R5 viruses reveals robust entry of infectious HIV-1 cores into macrophages. Retrovirology 2014 Mar 21;11:25. doi: 10.1186/1742-4690-11-25
Gupta RK, Goodall RL, Ranopa M, Kityo C, Munderi P, Lyagoba F, Mugarura L, Gilks CF, Kaleebu P, Pillay D; DART Virology Group and Trial Team. High rate of HIV resuppression after viral failure on first-line antiretroviral therapy in the absence of switch to second-line therapy. Clin Infect Dis. 2014 Apr;58(7):1023-6. doi: 10.1093/cid/cit933.
Sutherland KA, Mbisa JL, Ghosn J, Chaix ML, Cohen Codar I, Hue S, Delfraissy JF, Delaugerre C, Gupta RK. Phenotypic characterization of virologic failure following lopinavir/ritonavir monotherapy using full-length gag-protease genes. Journal of Antimicrobial Chemotherapy 2014; 69 (12): 3340-3348
Mogambo B, Nazziwa J, Bbosa N, Ahluwahlia M, Gupta RK, Kaleebu P, Parry CM. The Arrival of Untreatable Multi-drug Resistant HIV-1 in sub-Saharan Africa, AIDS. 2014 Jun 1;28(9):1373-4.
Gupta RK, Marks M, Edwards SG, Smith K, Fletcher K, Lee SM, Ramsay A, Copas AJ, Miller RF. A declining CD4 count and diagnosis of HIV-associated Hodgkin lymphoma: do prior clinical symptoms and laboratory abnormalities aid diagnosis? PLoS One. 2014 Feb 4;9(2):e87442. doi: 10.1371/journal.pone.0087442.
Hill A, McBride A, Sawyer W, Clumeck N, Gupta RK. Resistance at Virological Failure Using Boosted Protease Inhibitors versus non Nucleoside Reverse Transcriptase Inhibitors as First Line Antiretroviral Therapy - Implications for Sustained Efficacy of ART in Resource Limited Settings. Journal of Infectious Diseases 2013; 207:S78-84
Gupta RK, Sultan BJ, Hill A, Davis DHJ, Gregson J, Sawyer W, Hamers RL, Ndembi N, Pillay D, Jordan MR & Bertagnolio S. Global trends in antiretroviral resistance in untreated HIV-1 infected individuals following ART roll-out in resource-limited settings: a global collaborative study and meta-regression analysis. The Lancet 2012. Oct 6;380(9849):1250-8.
Sauter D, Hué S, Petit SJ, PlantierJC, Towers GJ, Kirchhoff K & Gupta RK. HIV-1 Group P is unable to antagonize human tetherin by Vpu, Env or Nef. Retrovirology 2011; Dec 15;8(1):103.
Gupta RK, Kohli A, McCormick AL, Towers GJ, Pillay D, Parry CM. Full length HIV-1 Gag determines protease inhibitor susceptibility within in vitro assays. AIDS 2010;July 24(11):1651-1655
Gupta RK, Mlcochova P, Pelchen-Matthews A, Petit SJ, Mattiuzzo G, Pillay D, Takeuchi Y, Marsh M, Towers GJ. Simian Immunodeficiency Virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration. Proceedings of the National Academy of Sciences, USA 2009; Dec8; 106:20889-20894
Gupta RK, Hué S, Schaller T, Verschoor E, Pillay D and Towers GJ. Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. PLoS Pathogens 2009 May;5(5):e1000443.
Gupta RK, Hill A, Sawyer W, Cozzi-Lepri A, von Wyl V, Yerly S, Dias Lima V, Gunthard HF, Gilks C, Pillay D. Virological monitoring and resistance to first-line highly active antiretroviral therapy in adults infected with HIV-1 treated under WHO guidelines: a systematic review and meta-analysis. Lancet Infectious Diseases 2009;9(7):409-17.
Gupta R, Hill A, Sawyer AW, Pillay D. Emergence of drug resistance in HIV-1 infected patients after first-line highly active antiretroviral therapy (HAART): a systematic review of clinical trials. Clinical Infectious Diseases 2008; 47(5):712-22