The risk of hyperglycemia associated with use of dolutegravir among adults living with HIV in Kampala, Uganda: A case-control study

Abstract

Emerging evidence suggests a possible association between hyperglycemia and dolutegravir (DTG), a preferred first-line antiretroviral agent in sub-Saharan Africa (SSA). There is need for rigorous studies to validate this association in the face of increasing DTG use and burden of non-communicable diseases among people living with HIV (PLHIV). We conducted a case–control study to assess the risk of hyperglycemia associated with use of DTG among PLHIV attending Mulago ISS Clinic in Kampala. Cases had hyperglycemia while controls had no hyperglycemia as confirmed by fasting plasma glucose and oral glucose tolerance tests. Demographic, laboratory, and clinical data were collected using interviewer-administered questionnaires and medical record abstraction. Analysis compared cases and controls on DTG use prior to diagnosis of hyperglycemia while controlling for potential confounders using multivariable logistic regression. We included 204 cases and 231 controls. In multivariable analysis, patients with prior DTG use had seven times greater odds of subsequent diagnosis of hyperglycemia compared to those who had non-DTG-based regimens (adjusted odds ratio [aOR] 7.01, 95% CI 1.96–25.09). The odds of hyperglycemia also increased with age (56 years and above vs. 18–35, aOR 12.38, 95% CI 3.79–40.50) and hypertension (aOR 5.78, 95% CI 2.53–13.21). Our study demonstrates a strong association between prior DTG exposure and subsequent diagnosis of hyperglycemia. Given the benefits of DTG, wide-scale use, and the growing burden of diabetes mellitus (DM) in SSA, there is need for systematic screening for hyperglycemia and consideration of alternate regimens for those at risk for DM.

Weight Change Following Switch to Dolutegravir for HIV Treatment in Rural Kenya During Country Roll-Out

“…25 This study prompted changes in Ugandan guidelines to recommend against DTG use in individuals with diabetes. 26 A subsequent case-control study in Uganda found 7-fold increased odds of study-measured hyperglycemia with prior DTG exposure 27 ; however, the odds ratio for hyperglycemia with current DTG exposure was 0.07, and discontinuation of DTG in the absence of diabetes was very rare, raising concerns for channeling bias. Modeling estimates from the ADVANCE study estimate that there would be 3 additional cases of incident diabetes per 1000 people on EFV/ FTC/TDF than on DTG/FTC/TDF, with risk from modest DTG-associated weight gain offset by improved lipid profile.…”

Prevalence and influences of diabetes and prediabetes among adults living with HIV in Africa: a systematic review and meta‐analysis

“…Further research detailing the newer ART drugs used in recent studies and their specific contributions to the development of diabetes, if any, is required. This includes dolutegravir, an integrase inhibitor, which has been found to be more effective and better tolerated than older ART medications, leading to its recommended use as a preferred first‐ and second‐line ART by the World Health Organization [75]. Recent evidence from Africa describes greater odds of hyperglycaemia in PLHIV treated with dolutegravir compared with other ART regimens even after adjusting for potential confounders of age, BMI and co‐morbid hypertension [75].…”

“…This includes dolutegravir, an integrase inhibitor, which has been found to be more effective and better tolerated than older ART medications, leading to its recommended use as a preferred first‐ and second‐line ART by the World Health Organization [75]. Recent evidence from Africa describes greater odds of hyperglycaemia in PLHIV treated with dolutegravir compared with other ART regimens even after adjusting for potential confounders of age, BMI and co‐morbid hypertension [75]. If a wider body of research confirms these findings, systematic screening for diabetes and prediabetes prior to the use of dolutegravir may need to be incorporated into HIV treatment guidelines [75].…”

“…Recent evidence from Africa describes greater odds of hyperglycaemia in PLHIV treated with dolutegravir compared with other ART regimens even after adjusting for potential confounders of age, BMI and co-morbid hypertension [75]. If a wider body of research confirms these findings, systematic screening for diabetes and prediabetes prior to the use of dolutegravir may need to be incorporated into HIV treatment guidelines [75].…”

Associations of HIV and antiretroviral therapy with gestational diabetes in South Africa

“…Following this recommendation, South Africa began initiating or switching pregnant PWH from efavirenz (EFV)-based ART to DTG-based ART. DTG has been associated with weight gain, including in pregnancy, and reports of hyperglycemia in nonpregnant adults [14][15][16]. Currently, there are no data on HIV, ART, and GDM risk in pregnancy or postpartum diabetes mellitus risk among pregnant PWH in South Africa following the rollout of DTG.…”