The Incidence of Type 2 Diabetes Mellitus and Weight Gain in People Living with HIV Receiving a Dolutegravir-Based Antiretroviral Therapy in Addis Ababa, Ethiopia: A Pilot Single-Arm Historical Cohort Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Setting, Design, and Period
2.2. Population and Eligibility Criteria
2.3. Sample Size and Sampling Methods
2.4. Variables of the Study
2.5. Data Collection Instrument, Procedure, and Quality Assurance
2.6. Data Analysis
3. Results
3.1. Characteristics of Participants
3.2. Incidence Proportion and Related Characteristics of T2DM
3.3. Incidence of Weight Gain
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ART | Antiretroviral therapy |
3TC | Lamivudine |
AZT | Azathiopurine/Zidovudine |
BMI | Body mass index |
CD4+ | Center of Differentiation+ |
D4T | Stavudine |
DM | Diabetes mellitus |
DTG | Dolutegravir |
FPG | Fasting Plasma Glucose |
HAART | Highly active antiretroviral therapy |
HBV | Hepatitis B virus |
HCV | Hepatitis C virus |
HIV | Human Immune Virus |
LPV | Lopinavir |
LPV/r | Ritonavir-boosted Lopinavir |
NNRTI | Non-nucleoside reverse transcriptase inhibitor |
NRTI | Nucleoside reverse transcriptase inhibitor |
PI | Protease Inhibitor |
PLHIV | People living with HIV |
T2DM | Type 2 diabetes mellitus |
WHO | World Health Organization |
References
- Collaboration of Observational HIV Epidemiological Research Europe in EuroCoord; Lewden, C.; Bouteloup, V.; De Wit, S.; Sabin, C.; Mocroft, A.; Wasmuth, J.C.; van Sighem, A.; Kirk, O.; Obel, N.; et al. All-cause mortality in treated HIV-infected adults with CD4 ≥ 500/mm3 compared with the general population: Evidence from a large European observational cohort collaboration. Int. J. Epidemiol. 2012, 41, 433–445. [Google Scholar] [PubMed]
- Samad, F.; Harris, M.; Puskas, C.M.; Ye, M.; Chia, J.; Chacko, S.; Bondy, G.P.; Lima, V.D.; Montaner, J.S.; Guillemi, S.A. Incidence of diabetes mellitus and factors associated with its development in HIV-positive patients over the age of 50. BMJ Open Diabetes Res. Care 2017, 5, e000457. [Google Scholar] [CrossRef] [PubMed]
- Butt, A.A.; McGinnis, K.; Rodriguez-Barradas, M.C.; Crystal, S.; Simberkoff, M.; Goetz, M.B.; Leaf, D.; Justice, A.C. HIV infection and the risk of diabetes mellitus. AIDS 2009, 23, 1227–1234. [Google Scholar] [CrossRef] [PubMed]
- Shen, Y.; Wang, Z.; Liu, L.; Zhang, R.; Zheng, Y.; Lu, H. Prevalence of hyperglycemia among adults with newly diagnosed HIV/AIDS in China. BMC Infect. Dis. 2013, 13, 79. [Google Scholar] [CrossRef] [PubMed]
- Duong, M.; Petit, J.M.; Piroth, L.; Grappin, M.; Buisson, M.; Chavanet, P.; Hillon, P.; Portier, H. Association between Insulin Resistance and Hepatitis C Virus Chronic Infection in HIV-Hepatitis C Virus-Coinfected Patients Undergoing Antiretroviral Therapy. JAIDS J. Acquir. Immune Defic. Syndr. 2001, 27, 245. [Google Scholar] [CrossRef] [PubMed]
- van Vonderen, M.; Blumer, R.; Hassink, E.; Sutinen, J.; Ackermans, M.; van Agtmael, M.; Danner, S.A.; Serlie, M.J.; Reiss, P. Insulin sensitivity in multiple pathways is differently affected during zidovudine/lamivudine-containing compared with NRTI-sparing combination antiretroviral therapy. J. Acquir. Immune Defic. Syndr. 2010, 53, 186–193. [Google Scholar] [CrossRef] [PubMed]
- Addy, C.L.; Gavrila, A.; Tsiodras, S.; Brodovicz, K.; Karchmer, A.W.; Mantzoros, C.S. Hypoadiponectinemia Is Associated with Insulin Resistance, Hypertriglyceridemia, and Fat Redistribution in Human Immunodeficiency Virus-Infected Patients Treated with Highly Active Antiretroviral Therapy. J. Clin. Endocrinol. Metab. 2003, 88, 627–636. [Google Scholar] [CrossRef]
- Prioreschi, A.; Munthali, R.J.; Soepnel, L.; Goldstein, J.A.; Micklesfield, L.K.; Aronoff, D.M.; Norris, S.A. Incidence and prevalence of type 2 diabetes mellitus with HIV infection in Africa: A systematic review and meta-analysis. BMJ Open 2017, 7, e013953. [Google Scholar] [CrossRef]
- Brown, T.T.; Cole, S.R.; Li, X.; Kingsley, L.A.; Palella, F.J.; Riddler, S.A.; Visscher, B.R.; Margolick, J.B.; Dobs, A.S. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch. Intern. Med. 2005, 165, 1179–1184. [Google Scholar] [CrossRef]
- Fiseha, T.; Belete, A.G. Diabetes mellitus and its associated factors among human immunodeficiency virus-infected patients on anti-retroviral therapy in Northeast Ethiopia. BMC Res. Notes 2019, 12, 372. [Google Scholar] [CrossRef]
- Abebe, S.M.; Getachew, A.; Fasika, S.; Bayisa, M.; Girma Demisse, A.; Mesfin, N. Diabetes mellitus among HIV-infected individuals in follow-up care at University of Gondar Hospital, Northwest Ethiopia. BMJ Open 2016, 6, e011175. [Google Scholar] [CrossRef] [PubMed]
- Workneh, M.H.; Bjune, G.A.; Yimer, S.A. Prevalence and Associated Factors of Diabetes Mellitus among Tuberculosis Patients in South-Eastern Amhara Region, Ethiopia: A Cross Sectional Study. PLoS ONE 2016, 11, e0147621. [Google Scholar] [CrossRef] [PubMed]
- Ataro, Z.A.W.; Fayera, J.; Abdosh, T. Magnitude and associated factors of diabetes mellitus and hypertension among adult HIV-positive individuals receiving highly active antiretroviral therapy at Jugal Hospital, Harar, Ethiopia. HIV/AIDS Res. Palliat. Care 2018, 10, 181–192. [Google Scholar] [CrossRef] [PubMed]
- Gebrie, A.; Tesfaye, B.; Gebru, T.; Adane, F.; Abie, W.; Sisay, M. Diabetes mellitus and its associated risk factors in patients with human immunodeficiency virus on anti-retroviral therapy at referral hospitals of Northwest Ethiopia. Diabetol. Metab. Syndr. 2020, 12, 20. [Google Scholar] [CrossRef] [PubMed]
- Tesfaye, D.Y.; Kinde, S.; Medhin, G.; Megerssa, Y.C.; Tadewos, A.; Tadesse, E.; Shimelis, T. Burden of metabolic syndrome among HIV-infected patients in Southern Ethiopia. Diabetes Metab. Syndr. 2014, 8, 102–107. [Google Scholar] [CrossRef] [PubMed]
- Federal Ministry of Health (FMOH). National Consolidated Guidelines for Comprehensive HIV Prevention, Care and Treatment. Addis Ababa, Ethiopia. 2018. Available online: https://www.afro.who.int/sites/default/files/2019-04/National%20Comprehensive%20HIV%20Care%20%20Guideline%202018.pdf (accessed on 25 July 2022).
- Taha, H.; Das, A.; Das, S. Clinical effectiveness of dolutegravir in the treatment of HIV/AIDS. Infect. Drug Resist. 2015, 8, 339–352. [Google Scholar]
- WHO. Update of Recommendations on First- and Second-Line Antiretroviral Regimens; WHO/CDS/HIV/19.15; World Health Organization: Geneva, Switzerland, 2019.
- Hailu, W.; Tesfaye, T.; Tadesse, A. Hyperglycemia After Dolutegravir-Based Antiretroviral Therapy. Int. Med. Case Rep. J. 2021, 14, 503–507. [Google Scholar] [CrossRef] [PubMed]
- Hirigo, A.T.; Gutema, S.; Eifa, A.; Ketema, W. Experience of dolutegravir-based antiretroviral treatment and risks of diabetes mellitus. SAGE Open Med. Case Rep. 2022, 10. [Google Scholar] [CrossRef]
- Aberash, E.; Worku, K. Could a Dolutegravir-Based Antiretroviral Therapy Lead to Clinical Obesity? A Retrospective Cohort Study Conducted at Hawassa University Comprehensive Specialized Hospital in Hawassa, Sidama, Ethiopia. AIDS Res. Treat. 2022, 2022, 2965325. [Google Scholar]
- Li, S.; Wang, J.; Zhang, B.; Li, X.; Liu, Y. Diabetes Mellitus and Cause-Specific Mortality: A Population-Based Study. Diabetes Metab. J. 2019, 43, 319–341. [Google Scholar] [CrossRef]
- Reis, A.F.N.; Lima, J.C.; Beccaria, L.M.; Ribeiro, R.C.H.M.; Ribeiro, D.F.; Cesarino, C.B. Hypertension and diabetes-related morbidity and mortality trends in a municipality in the countryside of São Paulo. Rev. Lat. Am. Enferm. 2015, 23, 1157–1164. [Google Scholar] [CrossRef] [PubMed]
- Moreira, R.C.; Pacheco, A.G.; Paula, A.; Cardoso, S.W.; Moreira, R.I.; Ribeiro, S.R.; Nunes, E.P.; Guimaraes, M.R.; Mello, F.C.; Veloso, V.G.; et al. Diabetes Mellitus is Associated with Increased Death Rates Among HIV-Infected Patients in Rio de Janeiro, Brazil. AIDS Res. Hum. Retroviruses 2016, 32, 1210–1218. [Google Scholar] [CrossRef] [PubMed]
- Kyaw, N.T.T.; Satyanarayana, S.; Oo, H.N.; Kumar, A.M.V.; Harries, A.D.; Aung, S.T.; Phyo, K.H.; Aung, T.K. Hyperglycemia and Risk of All-cause Mortality Among People Living with HIV With and Without Tuberculosis Disease in Myanmar (2011–2017). Open Forum Infect. Dis. 2018, 6, ofy355. [Google Scholar] [CrossRef]
- Kanters, S.; Renaud, F.; Rangaraj, A.; Zhang, K.; Limbrick-Oldfield, E.; Hughes, M.; Ford, N.; Vitoria, M. Evidence synthesis evaluating body weight gain among people treating HIV with antiretroviral therapy—A systematic literature review and network meta-analysis. eClinicalMedicine 2022, 48, 101412. [Google Scholar] [CrossRef]
- Muhammed, O.S.; Nasir, B.B. Drug Use Evaluation of Ceftriaxone in Ras-Desta Memorial General Hospital, Ethiopia. Drug Healthc. Patient Saf. 2020, 12, 161–168. [Google Scholar] [CrossRef] [PubMed]
- McLaughlin, M.; Walsh, S.; Galvin, S. Dolutegravir-induced hyperglycaemia in a patient living with HIV. J. Antimicrob. Chemother. 2018, 73, 258–260. [Google Scholar] [CrossRef]
- Jacomet, C.; Pugliese, P.; Delobel, P.; Katlama, C.; Joly, V.; Chidiac, C.; Cressey, T.R.; Mary, J.Y.; Salvadori, N.; Kosachunhanun, N. Incidence and clinical outcomes of diabetes mellitus in HIV-infected adults in Thailand: A retrospective cohort study. PLoS ONE 2018, 18, 1079. [Google Scholar]
- WHO. Physical Status: The Use and Interpretation of Anthropometry; Report of a WHO Expert Committee; World Health Organization: Geneva, Switzerland, 1995; Volume 854, p. 452.
- American Diabetes Association. Standards of Medical Care in Diabetes—2013. Diabetes Care 2013, 36 (Suppl. 1), S11–S66. [Google Scholar] [CrossRef] [PubMed]
- Namulindwa, A.; Wasswa, J.H.; Muyindike, W.; Tamukong, R.; Oloro, J. Prevalence and factors associated with adverse drug events among patients on dolutegravir-based regimen at the Immune Suppression Syndrome Clinic of Mbarara Regional Referral Hospital, Uganda: A mixed design study. AIDS Res. Ther. 2022, 19, 18. [Google Scholar] [CrossRef]
- Raffi, F.; Rachlis, A.; Stellbrink, H.J.; Hardy, W.D.; Torti, C.; Orkin, C.; Bloch, M.; Podzamczer, D.; Pokrovsky, V.; Pulido, F.; et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet 2013, 381, 735–743. [Google Scholar] [CrossRef]
- Cahn, P.; Pozniak, A.L.; Mingrone, H.; Shuldyakov, A.; Brites, C.; Andrade-Villanueva, J.F.; Richmond, G.; Buendia, C.B.; Fourie, J.; Ramgopal, M.; et al. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: Week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet 2013, 382, 700–708. [Google Scholar] [CrossRef] [PubMed]
- Selvin, E.; Parrinello, C.M. Age-related differences in glycaemic control in diabetes. Diabetologia 2013, 56, 2549–2551. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, Q.M.; Xu, J.H.; Chen, W.; Srinivasan, S.R.; Berenson, G.S. Correlates of age onset of type 2 diabetes among relatively young black and white adults in a community: The Bogalusa Heart Study. Diabetes Care 2012, 35, 1341–1346. [Google Scholar] [CrossRef] [PubMed]
- Savji, N.; Rockman, C.B.; Skolnick, A.H.; Guo, Y.; Adelman, M.A.; Riles, T.; Berger, J.S. Association between advanced age and vascular disease in different arterial territories: A population database of over 3.6 million subjects. J. Am. Coll. Cardiol. 2013, 61, 1736–1743. [Google Scholar] [CrossRef]
- Chia, C.W.; Egan, J.M.; Ferrucci, L. Age-Related Changes in Glucose Metabolism, Hyperglycemia, and Cardiovascular Risk. Circ. Res. 2018, 123, 886–904. [Google Scholar] [CrossRef] [PubMed]
- Fong, P.S.; Flynn, D.M.; Evans, C.D.; Korthuis, P.T. Integrase strand transfer inhibitor-associated diabetes mellitus: A case report. Int. J. STD AIDS 2017, 28, 626–628. [Google Scholar] [CrossRef]
- Ando, N.; Nishijima, T.; Mizushima, D.; Inaba, Y.; Kawasaki, Y.; Kikuchi, Y.; Oka, S.; Gatanaga, H. Long-term weight gain after initiating combination antiretroviral therapy in treatment-naïve Asian people living with human immunodeficiency virus. Int. J. Infect. Dis. 2021, 110, 21–28. [Google Scholar] [CrossRef]
- Bourgi, K.; Jenkins, C.A.; Rebeiro, P.F.; Palella, F.; Moore, R.D.; Altoff, K.N.; Gill, J.; Rabkin, C.S.; Gange, S.J.; Horberg, M.A.; et al. Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada. J. Int. AIDS Soc. 2020, 23, e25484. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
Variable | Category | Frequency | Percent |
---|---|---|---|
Sex | |||
Female | 110 | 59.5 | |
Male | 75 | 40.5 | |
Age category a | |||
38 years or less | 107 | 57.8 | |
>38 years | 78 | 42.2 | |
Marital status | |||
Single | 52 | 28.1 | |
Married | 94 | 50.8 | |
Widowed | 27 | 14.6 | |
Divorced/separated | 12 | 6.5 | |
Years since diagnosed with HIV | |||
7 years or less | 96 | 51.9 | |
>7 years | 89 | 48.1 | |
BMI when patient started DTG | |||
Underweight | 6 | 3.2 | |
Normal weight | 126 | 68.1 | |
Overweight | 50 | 27.0 | |
Obese | 3 | 1.6 | |
ART experience | |||
Naïve | 91 | 49.2 | |
Experienced/transferred in | 94 | 50.8 | |
Employment status | |||
Self-employed | 69 | 37.3 | |
Government-employed | 42 | 22.7 | |
Student | 24 | 13.0 | |
Unemployed | 18 | 9.7 | |
Privately employed | 32 | 17.3 | |
Comorbid status | |||
No | 175 | 94.6 | |
Yes | 10 | 5.4 |
Patient Characteristics | Incidence of T2DM | X2 Model Used | X2 Value | df | p-Value (Two-Tailed Test) | ||
---|---|---|---|---|---|---|---|
No (n = 172) | Yes (n = 13) | ||||||
Sex | Female | 104 | 6 | Continuity Correction | 0.519 | 1 | 0.471 |
Male | 68 | 7 | |||||
Employment status | |||||||
Self-employed | 64 | 5 | Likelihood Ratio | 8.445 | 4 | 0.077 | |
Government-employed | 41 | 1 | |||||
Student | 24 | 0 | |||||
Unemployed | 15 | 3 | |||||
Privately employed | 28 | 4 | |||||
Comorbid condition | |||||||
No | 164 | 11 | Fisher’s exact test | NA | NA | 0.149 | |
Yes | 8 | 2 | |||||
Treatment experience | |||||||
Naïve | 81 | 10 | Continuity Correction | 3.192 | 1 | 0.074 | |
Experienced/transferred in | 91 | 3 | |||||
Age category | |||||||
38 years or less | 106 | 1 | Continuity Correction | 12.291 | 1 | 0.000 | |
>38 years | 66 | 12 | |||||
Years since diagnosed with HIV | |||||||
7 years or less | 93 | 3 | Continuity Correction | 3.492 | 1 | 0.062 | |
>7 years | 79 | 10 | |||||
BMI when patient started dolutegravir | |||||||
Underweight | 5 | 1 | Likelihood Ratio | 1.231 | 3 | 0.746 | |
Optimal weight | 118 | 8 | |||||
Overweight | 46 | 4 | |||||
Obese | 3 | 0 |
Age Category | Marital Status Category | Incidence of T2DM | X2 Model Used | X2 Value | df | p-Value (Two-Tailed) | |
---|---|---|---|---|---|---|---|
No | Yes | ||||||
38 years or less | Single | 45 | 1 | Likelihood Ratio | 1.701 | 3 | 0.637 |
Married | 50 | 0 | |||||
Widowed | 6 | 0 | |||||
Divorced/Separated | 5 | 0 | |||||
>38 years | Single | 6 | 0 | Likelihood Ratio | 9.229 | 4 | 0.056 |
Married | 39 | 5 | |||||
Widowed | 18 | 3 | |||||
Divorced/Separated | 3 | 4 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Shimels, T.; Bilal, A.I.; Samuel, D.; Gedamu, D.; Solomon, E.; Shewamene, Z. The Incidence of Type 2 Diabetes Mellitus and Weight Gain in People Living with HIV Receiving a Dolutegravir-Based Antiretroviral Therapy in Addis Ababa, Ethiopia: A Pilot Single-Arm Historical Cohort Study. Venereology 2024, 3, 96-106. https://doi.org/10.3390/venereology3020008
Shimels T, Bilal AI, Samuel D, Gedamu D, Solomon E, Shewamene Z. The Incidence of Type 2 Diabetes Mellitus and Weight Gain in People Living with HIV Receiving a Dolutegravir-Based Antiretroviral Therapy in Addis Ababa, Ethiopia: A Pilot Single-Arm Historical Cohort Study. Venereology. 2024; 3(2):96-106. https://doi.org/10.3390/venereology3020008
Chicago/Turabian StyleShimels, Tariku, Arebu Issa Bilal, Desta Samuel, Desalew Gedamu, Eden Solomon, and Zewdneh Shewamene. 2024. "The Incidence of Type 2 Diabetes Mellitus and Weight Gain in People Living with HIV Receiving a Dolutegravir-Based Antiretroviral Therapy in Addis Ababa, Ethiopia: A Pilot Single-Arm Historical Cohort Study" Venereology 3, no. 2: 96-106. https://doi.org/10.3390/venereology3020008