Uptake and outcomes of generic dolutegravir based antiretroviral therapy in Georgia

Nikoloz Chkhartishvili, Nino Rukhadze, Lali Sharavdze, Pati Gabuni, Natalia Bolokadze, Nati Dvali, Otar Chokoshvili, Tengiz Tsertsvadze


Background: In July 2018 the World Health Organization updated antiretroviral therapy guidelines to recommend dolutegravir (DTG) as preferred first line drug. DTG was introduced in Georgia in 2017 and since 2018 has been prescribed as preferred first line option.

 Aim: We aimed to describe uptake of DTG in Georgia and evaluate outcomes of DTG-based antiretroviral therapy.

Materials and Methods: Study included all patients initiating DTG based treatment between July 1, 2017 and June 10, 2019. Data on patient demographic, epidemiological, clinical and laboratory parameters were extracted from the national AIDS health information system. Virologic response was evaluated in patients receiving DTG-based antiretroviral therapy at least for 6 months period. Viral suppression was defined as viral load (VL) <200 copies/ml. Missing VL data among patients on DTG based treatment for more than 12 months and discontinuation of therapy were defined as a failure (VL >200 copies/ml). Factors associated with achieving viral suppression were evaluated in multivariable Cox proportional hazards regression analysis.

Results: A total 635 patients initiated DTG-based therapy, among them the median age was 40 (IQR: 32-48) years, 459 (72.3%) were men, 326 (51.3%) were infected through heterosexual contact, 169 (26.6%) through injection drugs use and 123 (19.4%) through sex between men. Overall 487 (76.7%) patients received DTG as part of their first line regimen and 148 (23.3%) – as part of second line treatment. Per quarter uptake of DTG increased by 300% from 31 persons initiating DTG-based antiretroviral therapy in Jul-Sep 2017 to 124 persons in Apr-Jun 2019. Tenfovovir/emtricitabine + DTG was most commonly prescribed combination (n=510, 80.3%), followed by zidovudine/lamivudine + DTG (n=55, 8.7%), abacavir/lamivudine + DTG (n=29, 4.6%), dual-drug combination of ritonavir boosted protease inhibitor + DTG 41 (n=41, 6.5%). Of 635 patients initiating DTG-based treatment 13 patients died and 11 patients switched to other ART.. Remaining 611 patients were followed for the median 7.8 (IQR: 3.2-11.7) months. A total 369 patients were evaluable for virologic outcomes, including 363 patients remaining on DTG-based ART and 6 patients completely discontinuing ART. Among 369 patients assessed for virologic outcomes 339 (91.9%) patients had viral suppression at the last viral load measurement. Viral suppression rate was 92.9% among persons on first-line treatment and 88.8% among persons on second-line treatment. In multivariate analysis receiving first-line treatment was significantly association with achieving viral suppression (Hazard ratio: 1.58, 95% CI: 1.20-2.08, p=0.001), while time since HIV diagnosis per additional year was inversely associated with the outcome of interest (Hazard ratio: 0.92, 95% CI: 0.89-0.95, p<0.0001).

Conclusions: DTG has been successfully introduced in Georgia and the uptake has been increasing over time. Early results show effectiveness of DTG both in first- and second-line treatments. Treatment uptake, retention and viral suppression should be further monitored to inform national ART program.



Antiretroviral therapy; Dolutegravir; Georgia; Eastern Europe.

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Wandeler G, Johnson LF, Egger M. Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe: comparisons with general population. Curr Opin HIV AIDS. 2016 Sep;11(5):492-500.

UNAIDS. New high-quality antiretroviral therapy to be launched in South Africa, Kenya and over 90 low- and middle-income countries at reduced price. Geneva: UNAIDS; 2017 [cited 2020 January 24]; Available from: http://www.unaids.org/en/resources/presscentre/pressreleaseandstatementarchive/2017/september/20170921_TLD.

Dorward J, Lessells R, Drain PK, Naidoo K, de Oliveira T, Pillay Y, et al. Dolutegravir for first-line antiretroviral therapy in low-income and middle-income countries: uncertainties and opportunities for implementation and research. The Lancet HIV. 2018;5(7):e400-e4.

World Health Organization. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV: interim guidance. Geneva: WHO; 2018.

Tsertsvadze T, Chkhartishvili N, Sharvadze L, Dvali N, Chokoshvili O, Gabunia P, et al. Outcomes of Universal Access to Antiretroviral Therapy (ART) in Georgia. AIDS Res Treat. 2011;2011:621078.

Chkhartishvili N, Sharavdze L, Chokoshvili O, DeHovitz JA, del Rio C, Tsertsvadze T. The cascade of care in the Eastern European country of Georgia. HIV Med. 2015 Jan;16(1):62-6.

Chkhartishvili N, Sharvadze L, Chokoshvili O, Bolokadze N, Rukhadze N, Kempker RR, et al. Mortality and causes of death among HIV-infected individuals in the country of Georgia: 1989-2012. AIDS Res Hum Retroviruses. 2014 Jun;30(6):560-6.

Sidibe M, Loures L, Samb B. The UNAIDS 90-90-90 target: a clear choice for ending AIDS and for sustainable health and development. J Int AIDS Soc. 2016;19(1):21133.

Prabhu VR, Wong C, Jenkins S, Nizami S, Catlin K, P. D. New ARVs could represent over USD 3 billion in cost savings through 2025. (Absrtact No: 1050). Conference on Retroviruses and Opportunistic Infections (CROI 2016); Boston, USA2016.

Cruciani M, Parisi SG. Dolutegravir based antiretroviral therapy compared to other combined antiretroviral regimens for the treatment of HIV-infected naive patients: A systematic review and meta-analysis. PlOS One. 2019;14(9):e0222229.

Kumarasamy N, Prabhu S, Chandrasekaran E, Poongulali S, Pradeep A, Chitra D, et al. Safety, Tolerability, and Efficacy of Generic Dolutegravir-containing Antiretroviral Therapy Regimens Among South Indian Human Immunodeficiency Virus-infected Patients. Clin Infect Dis. 2019;68(6):1048-51.

Aboud M, Kaplan R, Lombaard J, Zhang F, Hidalgo JA, Mamedova E, et al. Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial. Lancet Infect Dis. 2019 Mar;19(3):253-64.

Brown D, Wang R, Underwood M, Hopking J, Nascimento MC, Aboud M, et al., editors. DTG vs. LPV/r (DAWNING): Efficacy by baseline NRTI reistsance and second-line NRTI use. (Abstract No: 144). Conference on Retroviruses and Opportunistic Infections (CROI 2019); 2019; Seattle, USA.

Chkhartishvili N, Sharvadze L, Dvali N, Karchava M, Rukhadze N, Lomtadze M, et al. Virologic outcomes of second-line antiretroviral therapy in Eastern European country of Georgia. AIDS Res Ther. 2014;11:18.

Penafiel J, de Lazzari E, Padilla M, Rojas J, Gonzalez-Cordon A, Blanco JL, et al. Tolerability of integrase inhibitors in a real-life setting. J Antimicrob Chemother. 2017 Jun 1;72(6):1752-9.

Hoffmann C, Welz T, Sabranski M, Kolb M, Wolf E, Stellbrink HJ, et al. Higher rates of neuropsychiatric adverse events leading to dolutegravir discontinuation in women and older patients. HIV Med. 2017 Jan;18(1):56-63.

Cuzin L, Pugliese P, Katlama C, Bani-Sadr F, Ferry T, Rey D, et al. Integrase strand transfer inhibitors and neuropsychiatric adverse events in a large prospective cohort. J Antimicrob Chemother. 2019 Mar 1;74(3):754-60.

Greenberg L, Ryom L, Wandeler G, Grabmeier-Pfistershammer K, Ollinger A, Neesgaard B, et al. Uptake and discontinuation of integrase inhibitors (INSTIs) in a large cohort setting. J Acquir Immune Defic Syndr. 2020 Jan 8.

Eckard AR, McComsey GA. Weight gain and integrase inhibitors. Curr Opin Infect Dis. 2020 Feb;33(1):10-9.

Zash R, Holmes L, Diseko M, Jacobson DL, Brummel S, Mayondi G, et al. Neural-Tube Defects and Antiretroviral Treatment Regimens in Botswana. N Engl J Med. 2019;381(9):827-40.

Zash R, Holmes L, Diseko M, Jacobson D, Brummel S, Mayondi G, et al., editors. Neural tube defects by antiretroviral and HIV exposure in the Tsepamo Study, Botswana. (Abstract No: MOAX0105LB). 10th IAS Conference on HIV Science (IAS 2019); 2019; Mexico City, Mexico.

Pereira G, Kim A, Jalil E, Fernandes Fonseca F, Shepherd B, Veloso V, et al., editors. No occurrences of neural tube defects among 382 women on dolutegravir at pregnancy conception in Brazil. (Abstract No. MOAX0104LB) 10th IAS Conference on HIV Science (IAS 2019); 2019; Mexico City, Mexico.

Waitt C, Orrell C, Walimbwa S, Singh Y, Kintu K, Simmons B, et al. Safety and pharmacokinetics of dolutegravir in pregnant mothers with HIV infection and their neonates: A randomised trial (DolPHIN-1 study). PLOS Medicine. 2019;16(9):e1002895.

Kintu K, Malaba T, Nakibuka J, Papamichael C, Colbers A, Seden K, et al. RCT of dolutegravir vs. efavirenz-based therapy initiated din ate pregnancy: DoLPHIN-2. (Absrtact No: 40). Conference On Retroviruses and Opportunistic Infections (CROI 2019); Seattle, USA2019.

Tserstvadze T, Chkhartishvili N, Gabunia P, Bolokadze N, Lomtadze M, Sharavdze L, et al. Consolidated guidelines on the use of antiretroviral drugs to treat and prevent HIV infection: National clinical practice guidelines Tbilisi: Ministry of Labour, Health and Social Affairs of Georgia; 2018.


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