Professor Ravindra Gupta

Honorary staff

About

Research in the Gupta lab focusses on host-pathogen and drug-pathogen interactions to inform HIV treatment and curative strategies.

Research summary

The Gupta lab has teams in both London and at the Africa Health Research Institute in Durban South Africa. Our work focuses on two areas:

• Studying in vitro HIV drug resistance to protease inhibitors and implications for global scale up of antiretroviral therapy
• Investigating the details of macrophage infection in clinical isolates. Macrophages are a crucial component of the immune system and a unique cell type in terms of access to sanctuary sites, thus representing a difficult-to-treat reservoir.

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.

Selected publications

• 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 AJ, 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 Apr;568:244-248
• 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, Giron A, Hamers R, Inzaule S, 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 before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis. Lancet Infect Dis. 2018;18:346-355
• Mlcochova P, Sutherland KA, Watters SA, Bertoli C, de Bruin RA, Rehwinkel J, Neil SJ, Lenzi GM, Kim B, Khwaja A, Gage MC, Georgiou C, Chittka A, Yona S, Noursadeghi M, Towers GJ, Gupta RK. A G1-like state allows HIV-1 to bypass SAMHD1 restriction in macrophages. EMBO J. 2018;37:50-62
• Kugathasan R, Collier DA, Haddow LJ, El Bouzidi K, Edwards SG, Cartledge JD, Miller RF, Gupta RK. Diffuse White Matter Signal Abnormalities on Magnetic Resonance Imaging Are Associated With Human Immunodeficiency Virus Type 1 Viral Escape in the Central Nervous System Among Patients With Neurological Symptoms. Clin Infect Dis. 2017;64:1059-1065
• Mlcochova P, Caswell SJ, Taylor IA, Towers GJ, Gupta RK. DNA damage induced by topoisomerase inhibitors activates SAMHD1 and blocks HIV-1 infection of macrophages. EMBO J. 2017;pii:e201796880
• 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 HIV-1 drug resistance to thymidine analogues following failure of first-line tenofovir combined with a cytosine analogue and nevirapine or efavirenz in sub Saharan Africa: a retrospective multi-centre cohort study. Lancet Infect Dis. 2017;17:296-304
• Sutherland KA, Collier DA, Claiborne DT, Prince JL, Deymier MJ, Goldstein RA, Hunter E, Gupta RK. Wide variation in susceptibility of transmitted/founder HIV-1 subtype C Isolates to protease inhibitors and association with in vitro replication efficiency. Sci Rep. 2016;6:38153
• Gregson J, Tang M, Ndembi N…., 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. 2016;16:565-75
• Smith NM, Mlcochova P, Watters SA, Aasa-Chapman MM, Rabin N, Moore S, Edwards SG, Garson JA, Grant PR, Ferns RB, Kashuba A, Mayor NP, Schellekens J, Marsh SG, 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;61:120-8
• Gupta RK, Jordan MR, Sultan BJ, Hill A, Davis DH, Gregson J, Sawyer AW, Hamers RL, Ndembi N, Pillay D, Bertagnolio S. Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis. Lancet. 2012;380:1250-8.