A study of insulin resistance in human immunodeficiency virus patients on antiretroviral therapy and its correlation with CD4 counts, disease duration in a tertiary care centre

INTRODUCTION

Human immunodeficiency virus (HIV) is a chronic illness that affects the immune system and leads to acquired immunodeficiency syndrome. Antiretroviral therapy (ART) is the standard treatment for HIV and has improved the survival rates. However, ART therapy is associated with metabolic complications, including insulin resistance (IR), which can increase the risk of developing diabetes mellitus and other chronic diseases. The physiology of this is not known exactly.

IR is a common metabolic complication among individuals with HIV and has been well documented in previous studies. The prevalence of IR in HIV patients who are on ART has been reported to range from 25% to 60%.^[1,2] The underlying mechanisms of IR in HIV patients are not yet fully understood, but factors such as oxidative stress, inflammation and ART-related toxicity are believed to contribute to its genesis.^[3,4]

The correlation between CD4 counts and IR has been widely studied in HIV patients on ART. Low CD4 counts have been shown to be associated with increased IR in several studies.^[5,6]

In a study done by Cholongitas et al., the authors found that individuals with a CD4 count <200 cells/mm³ had a higher prevalence of IR compared to those with higher CD4 counts. Kopp et al. also found a correlation between low CD4 counts and IR in a larger cohort of HIV-positive individuals.^[5,6]

The duration of the disease has also been shown to be associated with IR in HIV patients on ART. Several studies have reported that the longer the disease duration, the more the IR.^[2,7] In a study done by Shikuma et al., the authors found that individuals with a disease duration of more than 10 years had a higher prevalence of IR compared to those with a shorter disease duration.^[7]

Therefore, IR is a common metabolic complication in HIV patients on ART and is associated with several factors, such as low CD4 counts and longer disease duration. Further studies are needed for a better understanding of its underlying mechanisms and to develop interventions to prevent or manage IR in this population.

This study was conducted to evaluate the incidence of IR among HIV patients on ART therapy and to study the correlation between CD4 counts and duration of the disease.

MATERIALS AND METHODS

A cross-sectional study was conducted in a hospital-based outpatient clinic among HIV-positive patients who were on ART therapy for at least 6 months. The study included 51 patients who were recruited through consecutive sampling. The following data were collected: Demographic information, medical history, ART regimen, CD4 counts, fasting plasma glucose and insulin levels. IR was determined using the homeostasis model assessment of IR (HOMA-IR) formula. All the patients were on oral antiretroviral drug therapy with a combination of Tenofovir 300 mg once daily, Lamivudine 300 mg once daily and Dolutegravir 50 mg once daily. All patients above 18 years and diagnosed with HIV on stable ART for at least 6 months before enrolment were included in the study. Patient who were not willing to give consent and aged below 18 years, those with type 2 diabetes mellitus as per American Diabetes Association (ADA) guidelines and having any other medical conditions (e.g., liver disease and chronic kidney disease) that could affect glucose metabolism or insulin sensitivity, those having any history of substance abuse and medications that could affect glucose metabolism or insulin sensitivity other than ART were being excluded from the study.

RESULTS

The study included 51 participants, with most of them in the age group of 41–50 years, with a mean age being 41.37 years [Table 1]. The majority of the participants (58.82%) had IR [Table 2]. Based on the CD4 counts, there were three groups: Group A: <200 cells/mm³, Group B: 201–500 cells/mm³ and Group C: ≥501 cells/mm³. IR was observed in 50%, 60% and 66.67% of participants in groups A, B and C, respectively [Table 3]. The Chi-square test was performed to evaluate the association between CD4 counts and IR, and the results showed that there was no significant association (P = 0.6360). This suggests that the presence of IR is not significantly associated with CD4 counts in our study population. There was a weak positive correlation between CD4 counts and IR (as measured by fasting insulin and HOMA-IR). The correlation coefficient (Spearman R) was 0.2402 and 0.2352, respectively [Table 4]. This means that the correlation between CD4 counts and IR was not statistically significant, meaning that the two variables did not have a strong relationship, but have some which need to be followed up for a longer duration with a larger population size. On application of Mann–Whitney test for IR and duration of the disease, there was no significant difference in the duration of the disease between the groups with the absence and presence of IR (P = 0.4051) [Table 5]. The mean HOMA IR and fasting blood sugars for various groups are shown in Table 6.

The correlation between the duration of the disease (in years) and fasting insulin levels, as well as HOMA IR, are analysed. For fasting insulin levels, the correlation coefficient was 0.0361, which indicates a weak positive correlation between the duration of the disease and fasting insulin levels [Figure 1]. The t = 0.2528 and P = 0.8015 suggest that this correlation is not statistically significant. For HOMA IR, the correlation coefficient is 0.0175, which indicates an even weaker positive correlation between the duration of the disease and HOMA IR. Although the p-value is not significant, there is a small amount of positive correlation, which, however, needs a large population and longer follow-up.

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Figure 1:

Scatter plot: Fasting insulin versus duration of disease (in years). r² = 0.001, corrected r² = 0.019, P = 0.8015 (calculated by the Spearman correlation test).

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DISCUSSION

The results of this study suggest that IR was a common metabolic complication among the study population, with the majority (58.82%) of the participants being affected. However, there was no significant association between IR and CD4 counts (P = 0.6360), suggesting that the presence of IR was not significantly related to CD4 counts in this population. The mean CD4 count is slightly higher in the group with IR (425.93) compared to the group without IR (366.24), but the difference is not statistically significant (P = 0.1997). The weak positive correlation between CD4 counts and IR (Spearman R = 0.2402 and 0.2352 for fasting insulin and HOMA-IR, respectively) and non-significant p-values suggest that there was no strong relationship between these two variables.

In terms of the duration of disease, the results showed that there was no significant difference in the duration of disease between the groups with or without IR (P = 0.4051). The weak positive correlation between the duration of the disease and fasting insulin levels (Spearman R = 0.0361) and HOMA IR (Spearman R = 0.0175) is not statistically significant, as indicated by the non-significant P-values (0.8015 and 0.9027, respectively). These findings suggest that there was no significant correlation between the duration of the disease and either fasting insulin levels or HOMA IR.

The results of this study were consistent with the previous studies that have investigated the association between IR and CD4 counts in individuals with HIV.^[8,9] In these studies, no significant association was found between IR and CD4 counts, suggesting that IR is not a major determinant of CD4 count in individuals with HIV. However, some studies have reported a significant correlation between IR and CD4 counts, highlighting the need for further research to fully understand the relationship between these two variables.^[10]

A study by Ekong et al. found that individuals with HIV had a higher prevalence of IR compared to healthy controls, but the presence of IR did not significantly impact CD4 counts in their study population.^[11] Another study by Wang et al. similarly found that IR was more common in individuals with HIV, but the relationship between IR and CD4 counts was not significant.^[12]

In contrast, some studies have reported a significant association between IR and CD4 counts in individuals with HIV. For example, a study by Adegboye et al. reported that IR was associated with lower CD4 counts, and another study by Santos et al. found that IR was an independent predictor of CD4 count decline in individuals with HIV.^[13,14] These conflicting results highlight the need for further research to fully understand the relationship between IR and CD4 counts in individuals with HIV.

In terms of the duration of the disease, this study’s results are in line with a study by Obeng et al., which found no significant difference in the duration of HIV infection between individuals with and without IR.^[15] However, a study by Fang et al. reported that individuals with HIV and IR had a shorter duration of HIV infection compared to those without IR.^[16] Further research is needed to clarify the relationship between the duration of HIV infection and IR.

Finally, the weak and non-significant correlations between the duration of the disease and fasting insulin levels or HOMA IR were consistent with a study done by Liu et al., which found no significant correlation between the duration of HIV infection and metabolic markers in individuals with HIV.^[17] These findings suggest that the duration of HIV infection may not be a significant predictor of metabolic dysfunction in individuals with HIV.

CONCLUSION

The results of this study suggest that IR is a common metabolic complication among individuals with HIV. The physiology of this mechanism is diverse and not known exactly. There is a weak positive correlation between IR with CD4 counts and disease duration. Further larger studies are needed to fully understand the relationship between IR and CD4 counts and the duration of the disease in individuals with HIV.