The association between HIV tri-therapy with the development of Type-2 Diabetes Mellitus in a rural South African District: A case-control study

Abstract

Background Combination antiretroviral drugs (cARVs) prolong patients’ lives but are unfortunately thought to increase complications related to metabolic disorders including type-2 Diabetes Mellitus (DM). We sought to confirm the association of cARVs with type-2 DM and ascertain the extent of this association in a rural South African setting. Methods A case-control study of 177 (33.33%) cases with HIV/AIDS and type-2 DM were selected and compared with 354 (66.67%) non-DM HIV/AIDS unmatched controls from a rural district of South Africa’s third most populous province (Eastern Cape). Cases were identified from community health centres using the district health information system, and controls were identified using simple random sampling from the same health facilities. Odds Ratios (OR), together with 95% confidence intervals, were calculated for all the univariable and multivariable logistic analyses. Results This study found that cARVs significantly increased the occurrence of type-2 DM among HIV patients. Patients on protease inhibitors (PIs) were at least 21 times significantly (p<0.0001) more likely to be diabetic than those on the fixed dose combination (FDC); those on stavudine (D4T) and zidovudine (AZT) were 2.45 times and 9.44 times respectively more likely to be diabetic than those on FDC (p<0.05). The odds of diabetes increased by more than three-folds for those who had been on antiretroviral drugs for more than 6 years (p<0.005). Conclusion This study has been able to establish the association between cARVs and type-2 DM. It therefore proposes consideration of the usage of AZT, D4T, lopivavir and ritonavir for the treatment of HIV. The study further proposes more prospective research to test these findings further.

Lifestyle determinants of diabetes mellitus amongst people living with HIV in the Eastern Cape province, South Africa

“… 1 This is besides the established association between combined antiretroviral treatment (ARV) and DM. 2 , 3 , 4 , 5 Indicators of obesity such as weight, body fat percentage, waist–hip circumference and body mass index (BMI) that are above the designated values are known to forecast DM. 4 , 6…”

“…It is further hypothesised that viral load fluctuations cause life-long inflammation, which in turn leads to DM because of the resultant insulin resistance; patients with low levels of cluster of differentiation 4 (CD4) count were reported to have higher problems with glucose metabolism than those with higher CD4 counts and through poorly understood mechanisms ARVs are highly associated with the prevalence of DM. 2 , 3 , 4 , 9 , 10 Thus, greater risks for DM amongst PLWHIV are consistently and significantly associated with HIV disease progression. 4 , 9 , 10 …”

“…Even though ARVs should improve the immune status of PLWHIV, however, comorbid HIV and DM aggravated by ARVs has immunosuppressive consequences that create multiple complications for the sufferers and hasten deterioration, reduce quality healthcare and may result in death. 2 , 11 , 12 Regardless of the HIV status, obese and overweight patients should have a balanced lifestyle that aims for the loss of 5% – 7% of their initial weight in order to improve insulin sensitivity, control hyperglycaemia and maintain overall quality of life. 13 , 14 …”

“… 12 Furthermore, South Africa has the highest global HIV and DM comorbid prevalence. 2 A study conducted in the Eastern Cape, one of its rural provinces found a 21 times significantly higher association of being diabetic for PLWHIV on protease inhibitors (PIs) when compared with those on the fixed dose combination (FDC) of tenofovir, emtricitabine and efavirenz ( p < 0.0001); stavudine (D4T) and zidovudine (AZT) were also reported to have higher associations with diabetes in comparison to patients on FDC ( p < 0.05). 2 Furthermore, that same study found a threefold higher association between a longer duration on ARVs and DM ( p < 0.005).…”

Silver Nanoparticles Conjugate Attenuates Highly Active Antiretroviral Therapy-Induced Hippocampal Nissl Substance and Cognitive Deficits in Diabetic Rats

“…Many drugs cause insulin resistance or impaired insulin secretion, leading to diabetes in individuals with risk factors. The association between highly active antiretroviral therapy (HAART) and the development of T2DM has been reported [3,4].…”