Weight Gain Following Dolutegravir Based Antiretroviral Therapy in HIV-Naive Patients: A Comparative Study at the Ambulatory Treatment Center of the Regional Hospital of Kaolack (Senegal)
Introduction: Initiation of antiretroviral therapy is often associated with weight gain. The objective of this study is to compare weight gain at 12 and 24 months after initiation of dolutegravir-based ART with other regimens and to determine the factors associated with weight gain of more than 10% at 24 months. Methods: We conducted an observational, longitudinal and retrospective study of a cohort of people living with HIV followed at Kaolack Regional Hospital between January 2015, and July 2023. Patients were divided into two groups: one group of patients receiving TLD and a second group receiving a regimen based on non-nucleoside inhibitors or protease inhibitors. In multivariate analysis, logistic regression was performed to determine the factors associated with weight gain greater than or equal to 10%. Results: Among the 203 patients who met the inclusion criteria, 70 were on a Dolutegravir-based regimen and 133 were on a non-nucleoside inhibitor or protease inhibitor-based regimen. The average age was 45 years ± 11.5 years, and women accounted for 73.5% of the population. More than half of the patients were classified as stage 3 or 4 according to the WHO clinical classification. The average weight change at 24 months was +8.51 kg for patients on dolutegravir versus +7.24 kg for patients on other regimens. A weight gain greater than or equal to 10% at 24 months was observed in 58.1% of patients, and the factors associated with this gain were female gender (OR: 1.98 (95% CI: 1.01 - 3.90); p = 0.04) and WHO clinical stage 3 and 4 (OR: 4.03 (95% CI: 1.30 - 7.04); p < 0.001). Conclusion: We report greater weight gain in patients on Dolutegravir-based regimens compared to other non-nucleoside and protease inhibitor-based regimens. However, DTG is not significantly associated with excessive weight gain in this cohort of HIV-positive patients.
References
[1]
Koethe, J.R., Jenkins, C.A., Lau, B., Shepherd, B.E., Justice, A.C., Tate, J.P., et al. (2016) Rising Obesity Prevalence and Weight Gain among Adults Starting Antiretroviral Therapy in the United States and Canada. AIDSResearchandHumanRetroviruses, 32, 50-58. https://doi.org/10.1089/aid.2015.0147
[2]
McLaughlin, M., Walsh, S. and Galvin, S. (2018) Dolutegravir-Induced Hyperglycaemia in a Patient Living with HIV. JournalofAntimicrobialChemotherapy, 73, 258-260. https://doi.org/10.1093/jac/dkx365
[3]
Agrawal, S. and Agrawal, P.K. (2016) Association between Body Mass Index and Prevalence of Multimorbidity in Low-and Middle-Income Countries: A Cross-Sectional Study. InternationalJournalofMedicineandPublicHealth, 6, 73-83. https://doi.org/10.5530/ijmedph.2016.2.5
[4]
Yuh, B., Tate, J., Butt, A.A., Crothers, K., Freiberg, M., Leaf, D., et al. (2015) Weight Change after Antiretroviral Therapy and Mortality. ClinicalInfectiousDiseases, 60, 1852-1859. https://doi.org/10.1093/cid/civ192
[5]
Achhra, A., Mocroft, A., Reiss, P., Sabin, C., Ryom, L., de Wit, S., et al. (2015) Short‐term Weight Gain after Antiretroviral Therapy Initiation and Subsequent Risk of Cardiovascular Disease and Diabetes: The D:A:D Study. HIVMedicine, 17, 255-268. https://doi.org/10.1111/hiv.12294
[6]
Podany, A.T., Scarsi, K.K. and Fletcher, C.V. (2016) Comparative Clinical Pharmacokinetics and Pharmacodynamics of HIV-1 Integrase Strand Transfer Inhibitors. ClinicalPharmacokinetics, 56, 25-40. https://doi.org/10.1007/s40262-016-0424-1
[7]
Park, T.E., Mohamed, A., Kalabalik, J. and Sharma, R. (2015) Review of Integrase Strand Transfer Inhibitors for the Treatment of Human Immunodeficiency Virus Infection. ExpertReviewofAnti-InfectiveTherapy, 13, 1195-1212. https://doi.org/10.1586/14787210.2015.1075393
[8]
Bourgi, K., Rebeiro, P.F., Turner, M., Castilho, J.L., Hulgan, T., Raffanti, S.P., et al. (2019) Greater Weight Gain in Treatment-Naive Persons Starting Dolutegravir-Based Antiretroviral Therapy. ClinicalInfectiousDiseases, 70, 1267-1274. https://doi.org/10.1093/cid/ciz407
[9]
Bai, R., Lv, S., Wu, H. and Dai, L. (2022) Effects of Different Integrase Strand Transfer Inhibitors on Body Weight in Patients with HIV/AIDS: A Network Meta-Analysis. BMCInfectiousDiseases, 22, Article No. 118. https://doi.org/10.1186/s12879-022-07091-1
[10]
Shikuma, C.M., Zackin, R., Sattler, F., Mildvan, D., Nyangweso, P., Alston, B., et al. (2004) Changes in Weight and Lean Body Mass during Highly Active Antiretroviral Therapy. ClinicalInfectiousDiseases, 39, 1223-1230. https://doi.org/10.1086/424665
[11]
Madec, Y., Szumilin, E., Genevier, C., Ferradini, L., Balkan, S., Pujades, M., et al. (2009) Weight Gain at 3 Months of Antiretroviral Therapy Is Strongly Associated with Survival: Evidence from Two Developing Countries. AIDS, 23, 853-861. https://doi.org/10.1097/qad.0b013e32832913ee
[12]
Mustapha, K.B., Ehianeta, T.S., Kirim, R.A., Osungwu, F.T. and Oladepo, D.K. (2011) Highly Active Antiretroviral Therapy (HAART) and Body Mass Index (BMI) Relationship in People Living with HIV/AIDS (PLWHA) in the Federal Capital Territory, Nigeria and the Neighbouring States. Journal of AIDS and HIV Research, 3, 57-62.
[13]
Kintu, A., Liu, E., Hertzmark, E., Spiegelman, D., Zack, R.M., Muya, A., et al. (2018) Incidence and Risk Factors for Overweight and Obesity after Initiation of Antiretroviral Therapy in Dar Es Salaam, Tanzania. JournaloftheInternationalAssociationofProvidersofAIDSCare(JIAPAC), 17, 1-10. https://doi.org/10.1177/2325958218759759
[14]
Xie, Y., Sun, J., Wei, L., Jiang, H., Hu, C., Yang, J., et al. (2021) Altered Gut Microbiota Correlate with Different Immune Responses to HAART in HIV-Infected Individuals. BMCMicrobiology, 21, Article No. 11. https://doi.org/10.1186/s12866-020-02074-1
[15]
Markakis, K., Tsachouridou, O., Georgianou, E., Pilalas, D., Nanoudis, S. and Metallidis, S. (2024) Weight Gain in HIV Adults Receiving Antiretroviral Treatment: Current Knowledge and Future Perspectives. Life, 14, Article 1367. https://doi.org/10.3390/life14111367
[16]
Sax, P.E., Erlandson, K.M., Lake, J.E., Mccomsey, G.A., Orkin, C., Esser, S., et al. (2019) Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials. ClinicalInfectiousDiseases, 71, 1379-1389. https://doi.org/10.1093/cid/ciz999
[17]
Hirigo, A.T., Yilma, D., Astatkie, A. and Debebe, Z. (2023) Effect of Dolutegravir-Based First-Line Antiretroviral Therapy on Weight and Body Mass Index among Adult People Living with HIV on Follow up at Health Facilities in Hawassa City Administration, Southern Ethiopia: A Retrospective Cohort Study. AnnalsofMedicine, 55, Article 2242250. https://doi.org/10.1080/07853890.2023.2242250
[18]
Namsal Anrs 12313 Study Group (2019) Dolutegravir-Based or Low-Dose Efavirenz–based Regimen for the Treatment of HIV-1. NewEnglandJournalofMedicine, 381, 816-826.
[19]
Venter, W.D.F., Sokhela, S., Simmons, B., Moorhouse, M., Fairlie, L., Mashabane, N., et al. (2020) Dolutegravir with Emtricitabine and Tenofovir Alafenamide or Tenofovir Disoproxil Fumarate versus Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate for Initial Treatment of HIV-1 Infection (ADVANCE): Week 96 Results from a Randomised, Phase 3, Non-Inferiority Trial. TheLancetHIV, 7, e666-e676. https://doi.org/10.1016/s2352-3018(20)30241-1
[20]
Esber, A.L., Chang, D., Iroezindu, M., Bahemana, E., Kibuuka, H., Owuoth, J., et al. (2022) Weight Gain during the Dolutegravir Transition in the African Cohort Study. JournaloftheInternationalAIDSSociety, 25, e25899. https://doi.org/10.1002/jia2.25899
[21]
Emond, B., Rossi, C., Côté-Sergent, A., Dunn, K., Lefebvre, P., Lafeuille, M., et al. (2021) Weight Change and Predictors of Weight Change among Patients Initiated on Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide or Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Real-World Retrospective Study. JournalofHealthEconomicsandOutcomesResearch, 8, 88-98. https://doi.org/10.36469/jheor.2021.2435
[22]
Domingo, P., Villarroya, F., Giralt, M. and Domingo, J.C. (2020) Potential Role of the Melanocortin Signaling System Interference in the Excess Weight Gain Associated to Some Antiretroviral Drugs in People Living with HIV. InternationalJournalofObesity, 44, 1970-1973. https://doi.org/10.1038/s41366-020-0551-5
[23]
McMahon, C., Trevaskis, J.L., Carter, C., Holsapple, K., White, K., Das, M., et al. (2020) Lack of an Association between Clinical INSTI-Related Body Weight Gain and Direct Interference with MC4 Receptor (MC4R), a Key Central Regulator of Body Weight. PLOSONE, 15, e0229617. https://doi.org/10.1371/journal.pone.0229617
[24]
Gorwood, J., Bourgeois, C., Pourcher, V., Pourcher, G., Charlotte, F., Mantecon, M., et al. (2020) The Integrase Inhibitors Dolutegravir and Raltegravir Exert Proadipogenic and Profibrotic Effects and Induce Insulin Resistance in Human/Simian Adipose Tissue and Human Adipocytes. ClinicalInfectiousDiseases, 71, e549-e560. https://doi.org/10.1093/cid/ciaa259
[25]
Dai, H., Alsalhe, T.A., Chalghaf, N., Riccò, M., Bragazzi, N.L. and Wu, J. (2020) The Global Burden of Disease Attributable to High Body Mass Index in 195 Countries and Territories, 1990-2017: An Analysis of the Global Burden of Disease Study. PLOSMedicine, 17, e1003198. https://doi.org/10.1371/journal.pmed.1003198
[26]
McComsey, G.A., Emond, B., Shah, A., Bookhart, B.K., Rossi, C., Milbers, K., et al. (2022) Association between Weight Gain and the Incidence of Cardiometabolic Conditions among People Living with HIV-1 at High Risk of Weight Gain Initiated on Antiretroviral Therapy. InfectiousDiseasesandTherapy, 11, 1883-1899. https://doi.org/10.1007/s40121-022-00673-1
[27]
Bares, S.H., Wu, X., Tassiopoulos, K., Lake, J.E., Koletar, S.L., Kalayjian, R., et al. (2023) Weight Gain after Antiretroviral Therapy Initiation and Subsequent Risk of Metabolic and Cardiovascular Disease. ClinicalInfectiousDiseases, 78, 395-401. https://doi.org/10.1093/cid/ciad545
[28]
Tesfaye, D.Y., Kinde, S., Medhin, G., Megerssa, Y.C., Tadewos, A., Tadesse, E., et al. (2014) Burden of Metabolic Syndrome among HIV-Infected Patients in Southern Ethiopia. Diabetes&MetabolicSyndrome: ClinicalResearch&Reviews, 8, 102-107. https://doi.org/10.1016/j.dsx.2014.04.008
[29]
Bares, S.H., Smeaton, L.M., Xu, A., Godfrey, C. and McComsey, G.A. (2018) HIV-Infected Women Gain More Weight than HIV-Infected Men Following the Initiation of Antiretroviral Therapy. JournalofWomen’sHealth, 27, 1162-1169. https://doi.org/10.1089/jwh.2017.6717
[30]
Lake, J.E., Wu, K., Bares, S.H., Debroy, P., Godfrey, C., Koethe, J.R., et al. (2020) Risk Factors for Weight Gain Following Switch to Integrase Inhibitor-Based Antiretroviral Therapy. ClinicalInfectiousDiseases, 71, e471-e477. https://doi.org/10.1093/cid/ciaa177
[31]
Palella, F.J., Hou, Q., Li, J., Mahnken, J., Carlson, K.J., Durham, M., et al. (2023) Weight Gain and Metabolic Effects in Persons with HIV Who Switch to ART Regimens Containing Integrase Inhibitors or Tenofovir Alafenamide. JAIDSJournalofAcquiredImmuneDeficiencySyndromes, 92, 67-75. https://doi.org/10.1097/qai.0000000000003101
[32]
Ando, N., Nishijima, T., Mizushima, D., Inaba, Y., Kawasaki, Y., Kikuchi, Y., et al. (2021) Long-Term Weight Gain after Initiating Combination Antiretroviral Therapy in Treatment-Naïve Asian People Living with Human Immunodeficiency Virus. InternationalJournalofInfectiousDiseases, 110, 21-28. https://doi.org/10.1016/j.ijid.2021.07.030
[33]
Shah, S., Pilkington, V. and Hill, A. (2021) Is Tenofovir Disoproxil Fumarate Associated with Weight Loss? AIDS, 35, S189-S195. https://doi.org/10.1097/qad.0000000000003083
