Study of metabolic complications after 1 year of antiretroviral therapy in HIV-infected patients in a tertiary care center in North Bengal

Aim: There are conflicting data regarding the incidence of metabolic abnormalities in human immunodeficiency virus (HIV)-naive patients on antiretroviral therapy (ART). Also, recommendations for the monitoring of fasting lipid and glucose by major world bodies is annually while this study demonstrates that significant changes occur in as early as 6 months. Design: The incidence and pattern of metabolic complications have been studied in a case series study design at a tertiary care center through 1 year of ART. Materials and Methods: One hundred and twenty patients were followed for 1 year after initiating ART. Data collection and categorization were done according to the statistical software application such as mean comparison and one-way analysis of variance (ANOVA) using the statistical software IBM-SPSS (version 19 Chicago Inc.) assuming the significance at 95% of confidence interval (CI). Results: At the baseline, total mean cholesterol was 162.25 mg/dL, triglyceride (TG) was 126.57 mg/dL, Low-density lipoprotein cholesterol (LDL-c) was 99.14 mg/dL and high-density lipoprotein cholesterol (HDL-c) was 36.96 mg/dL. At 6 months total cholesterol (TC), LDL-c, TG, and HDL-c increased by 12.49%, 15.01%, 14.93%, and 08.27%, respectively, and at 12 months these increased by 22%, 22.67%, 56.39%, and 14.98%, respectively, (P < 0.05). At the baseline, the mean fasting blood glucose (FBG) was 83.78 mg/dL while at 6 months and 12 months, the mean FBG was 88.18 mg/dL and 93.03 mg/dL, respectively, (P < 0.05). FBG was impaired in 11.9% and 17.8% of the patients at 6 months and 12 months, respectively. Diabetes was diagnosed in 4% of the patients at 12 months. Conclusion: ART has significant metabolic complications such as dyslipidemia, glucose intolerance, and increased body mass index (BMI) and requires proper monitoring and dose adjustment.

Keywords: Antiretroviral therapy (ART), metabolic complications, 1 year

Antiretroviral therapy (ART) can reduce the burden of human immunodeficiency virus (HIV) and restore the immune systems of HIV patients. The introduction of ART has dramatically reduced the incidence of opportunistic infections among HIV-positive people. ^[1],[2] With such a population level, the potential benefits versus deleterious effects of successful ART programs in a developing country like India, which is one of the worst affected countries, by the HIV pandemic have been widely argued. ^[3],[4] However, ART-related metabolic complications can cause reduction in the patient’s adherence level and increase his/her morbidity. Selected chronic complications associated with ART include hyperlipidemia, insulin resistance and diabetes mellitus (DM), lipodystrophy, and bone disorder such as osteopenia/osteoporosis. ^[5] Insulin resistance and its clinical associates like impaired glucose tolerance (IGT), DM, and dyslipidemia are increasing in HIV-infected persons. In June 1997, soon after the introduction of protease inhibitors (PIs), as a part of ART, metabolic complications have increased further. ^[6] Stavudine and PIs also cause hyperglycemia. Drugs causing dylipidemia are stavudine (d4T), efavirenz (EFV) and all boosted PIs (except atazanavir when used without ritonavir boosting). ^[7] We, therefore, realize the need to conduct such studies to assess the incidences of metabolic complications in North Eastern part of our country and whether this data is similar to the national data.

This study was conducted at the ART Centre of North Bengal Medical College under the Department of General Medicine on HIV/acquired immune deficiency syndrome (AIDS) patients attending the Medical Outpatient Department (MOPD) or ART Centre. It is a case series analytical study.

Inclusion criteria

1. ART-naïve HIV positive patients older than 12 years
2. First-line drug regime approved by National AIDS Control Organisation (NACO)

Exclusion criteria

1. Patients with poor adherence
2. Pediatric patients
3. Preexisting ischemic heart disease (IHD), DM, impaired glucose tolerance (IGT), and dyslipidemia at initiation.

NACO guidelines for the eligibility criteria of ART therapy were maintained. The patients who were started on ART were selected from the ART register. Newly registered patients from January 2010 to January 2011 were taken and each patient was followed up for 1 year. The patients were screened for impaired fasting glucose, DM, and dyslipidemia [high levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c)] at the beginning. Patients having IHD, impaired fasting blood glucose (FBG), DM, and dyslipidemia were excluded from the study. Sugar, lipid profile, abdominal girth, and body mass index (BMI) were estimated at the beginning and at every 6-month interval.

Data were collected, collated, and transferred to Excel spreadsheet (MS Excel 2007) and analyzed using IBM-SPSS version 16 Chicago Inc. All the statistical significance tests were done assuming level of significance at 95% confidence intervals (CIs).

Here, 120 diagnosed cases of HIV-infected patients who attended the ART Centre of North Bengal Medical College and Hospital for ART were selected for study. Relevant history taking, clinical examination, and investigations for opportunistic infections were done at the baseline after 6 months and 12 months. Follow-up data were available for 101 patients at 6 months and 12 months (10 patients died, 5 patients were lost to follow-up, and 5 were transferred out of the other ART center). Data of the patients who died and were lost to follow-up or those who were transferred to the other ART center were not included in this analysis. Patients of age group 18 onward were included with maximum patients being in the 30-39 age group.

Analysis of data revealed the following about metabolic complications:

1. The mean weight of the study population in this study was 45.09 kg at the baseline. After 6 months and 12 months of receiving highly active antiretroviral therapy (HAART), the mean weight increased. It was 46.73 kg and 48.19 kg after 6 months and 12 months, respectively. This change was not significant (P > 0.05) between the baseline and after 6 months of receiving HAART but it was significant (P < 0.05) between the baseline and after 12 months of receiving HAART.
2. The mean BMI of the study population was 17.33. It was increasing among this study population who were receiving HAART. After 6 months of HAART, it was 17.95 and after 12 months of HAART, it was 18.50. The change in mean of BMI in different time durations with HAART was significant (P < 0.05) [Table 1].
3. At the baseline TG, TC, and LDL-c were within normal limits and high-density lipoprotein cholesterol (HDL-c) level was <40 mg/dL in most of the cases (84.1%) among the study population. At the baseline, the mean of TC of the study population was 162.25 mg/dL, mean of TG was 126.57 mg/dL, mean of LDL-c was 99.14 mg/dL, and mean of HDL-c was 36.96 mg/dL [Table 2],[Table 3] and [Table 4].
4. After 6 months and 12 months of HAART, the mean of TG was 145.47 mg/dL and 173.20 mg/dL, the mean of TC was 182.52 mg/dL and 197.95 mg/dl, the mean of LDL-c was 114.03 mg/dL and 121.62 mg/dL, and the mean of HDL-c was 40.02 mg/dL and 42.50 mg/dL, respectively. These changes in the mean of TG, TC, HDL-c, and LDL-c at different time durations with HAART in the study population were significant (P < 0.05) except in the case of LDL-c between 6 months and 12 months after receiving HAART. However, in between the baseline and after 12 months of receiving HAART in the study population, it was significant (P < 0.05) [Table 2],[Table 3] and [Table 4].
5. At the baseline, FBG was within normal limits (<100 mg/dL) in all cases. After 6 months of HAART, FBG levels were impaired (>100 mg/dL to <126 mg/dL) in 12 (11.9%) cases. After 12 months, FBG levels were impaired (>100 mg/dL to <126 mg/dL) in 18 (17.8%) cases and diabetes was diagnosed (FBG ≥ 126 mg/dL) in four (4%) cases. At the baseline, the mean of FBG in the study population was 83.78 mg/dL. After 6 months and 12 months of HAART, the mean of FBG was 88.18 mg/dL and 93.03 mg/dL, respectively. These changes of FBG were statistically significant [Table 5].

The mean age of the patients in this study was 33.15 years. HIV sentinel surveillance and HIV estimation in 2006 in India showed that 88.7% of HIV cases were in the age group of 15-49 years of age and had a gender ratio of 1.56:1, which is almost equal in this study. The baseline TC, LDL-c level, and TG level were within the normal range, whereas HDL-c level was almost in the lower range. FBG level also was in the normal range at the baseline. After 12 months of successful ART, TC level, HDL-c level, TG level as well as LDL-c level increased significantly. Previous studies have shown that some antiretroviral drugs such as stavudine and PIs, increased blood level of TC, LDL-c, and TGs and have variable effects on levels of HDL-c [Table 6]. ^[8],[9] By contrast, ART regimens containing nonnucleoside reverse-transcriptase inhibitors (NNRTIs) have been less well studied, although receipt of nevirapine is associated with less atherogenic lipid profiles. ^[10]

Patients initiating ART in resource limited settings may experience different rates and types of lipid abnormalities than patients in resource-sufficient countries because of difference in genetic background, dietary intake, and lifestyle factors. In addition, these patients are more likely to have advanced HIV disease and poor nutritional status. A similar study from Pune, India, found that treatment with stavudine, lamivudine, and nevirapine was associated with substantial increase in TC and TG levels in HIV-infected patients treated for 18-20 months. ^[11] TC and LDL-c levels have routinely shown an increase with the use of effective ART. ^{[10],[12],[13]} A recent finding suggests that the use of NNRTI-based therapy results in an elevation in HDL-c levels and, therefore, may be less atherogenic than PI-based treatment. ^[14] Regimens containing nevirapine have been associated with more favorable changes in lipid profiles (lesser increase in TC, TG, LDL-c levels and greater increase in HDL-c level) than efavirenz-containing regimens. ^[15],[16] PI therapy directly affects blood glucose metabolism. Kathelien Mulligan et al. compared treatment of 20 HIV positive cases with PI, 9 cases with nucleoside reverse transcriptase inhibitors (NRTI), and 12 cases with no ART and observed that in PI-treated cases, there were elevated fasting insulin and blood glucose, and increased TG and LDL. They also observed signs of insulin resistance after 3.4 months on an average without body shape change at the time. ^[17]

The Indian population in general has a high risk of cardiovascular disease (because of genetic and other factors), and there is concern that HIV infection and treatment with HAART may increase the risk reference. Our observations that HIV/AIDS patients who receive the HAART have an abnormal lipid profile at 1 year should alert physicians to this outcome and encourage testing. Although the current World Health Organization guidelines do not recommend routine monitoring of lipid levels for patients receiving first-line antiretroviral treatment, patients would benefit from an assessment of lipid profiles and other cardiovascular risk factors followed by counseling on risk-reduction strategies. As patients continue to enjoy longer lives as a result of effective treatment, it is important to consider and minimize the long-term adverse effects of the disease and its treatment.

Recommendations for the monitoring of fasting lipid and glucose by major world bodies is annually while this study demonstrates that significant changes occur in as early as 6 months. Hence, monitoring should begin earlier to prevent future complications. Although increasing body weight signifies the patient’s well-being in a disease popularly known as “slim disease,” such metabolic alteration can cause severe complications that can become more lethal rather than the disease itself.

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1755-6783.177376

[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]