With rapid scale up of ART and the increasing usage of antiretroviral drugs to prevent HIV, the need to monitor side effects of these drugs has increased substantially. HIV-infected patients are known to have an increased risk of CVD compared with the general population, with a significantly elevated mortality rate from cardiovascular events [10]. Dyslipidemia represents significant health care concerns in HIV infected patients due to its direct association with increased CVD risk [11]. So that assessing of serum lipid profiles in HIV patients on ART help in early prediction of CVD.
The results of the current study revealed that there was a statistically significant difference between ATV/r- and EFV-treated groups in median TG values (p=0.011) (Figure 1). The likely explanation of elevated levels of TG on the ATZ/r-treated group might be due to the addition of low dose ritonavir which increases significantly serum or plasma TG levels [12, 13]. The results of our study are similar to those observed in comparative trails comparing EFV and ATV/r [14].
The study participants having TG ≥200mg/dL were higher in ATV/r-treated group (52.2%) as compared to EFV-treated group (26.7%). For ATV/r-treated group, it was higher than the prevalence reported from the study conducted in Barcelona-Spain by Podzamczer et al. [15] that compared ATV/r to nevirapine and found that 37.8% abnormal TG levels. This variation might be due to difference in the socio-economic status of study participants and duration of exposure to the treatment. The other possible explanation might be that some of the study participants in Podzamczer et al.’s study were on lipid lowering drugs.
For EFV-treated group, it was lower than the prevalence reported from the study conducted in Addis Ababa-Ethiopia by Belay et al. [16] which was 36.6%. This variation might be due to difference in the cut-off value used and sample size. In Belay et al., the cut of value was TG ≥ 150 mg/dL, which is lower than that used in our study (TG≥200mg/dL). Another possible explanation might be treatment duration that may contribute to the difference.
The average value of HDL-C was significantly lower (p=0.001) in the ATV/r-treated group as compared to EFV-treated group (Figure 1). Similar results were found in a randomized control trails that reported lower HDL-C in ATV/r-treated group than in EFV-treated group [17, 18]. Several confounding factors contribute to our observation. First, duration of current treatment with EFV-treated group is nearly double that of the ATV/r-treated group. Second, CD4 count was higher in the EFV-treated group as compared to ATV/r-treated group.
Available data also suggested that a long term therapy with EFV and its concentration is directly proportional to HDL-C levels [7]. In addition, genetic variation may also be attributed to the changes in HDL-C levels [19]. Interestingly, it has been shown that efavirenz-induced increase in HDL-C is influenced by the gene multi drug reasistance-1(MDR-1) polymorphism that codes for the drug transporter P-glycoprotein. Differences in the MDR-1 gene polymorphism have been related to the EFV concentration in plasma and to the immune recovery of CD4 lymphocyte cell counts [20].
The possible molecular mechanism by which EFV increase the HDL-C levels were through down regulation of the activity of the plasma cholesterol transfer protein (CETP) expression through antagonism of the lipid transcription factor, LXR. CETP, which is known to regulate human lipoprotein cholesterol ester to TG exchange and affect HDL-C levels [21].
In the same pattern, the average ratio of TG/HDL-C was significantly higher (p=0.001) in the ATV/r- treated group as compared to EFV-treated group of the present study (Figure 2). This is due to high levels of TG and low levels of HDL-C on the ATV/r-treated group as a result their ratio became high. Even if there is no similar study regarding the TG/HDL-C ratio, it has greater predictive power than each of the single standard lipid parameters and superior to the other ratios in order to predict insulin resistance [22]. Furthermore, a TG/HDL-C ratio of ≥3 has been shown to be closely correlated to insulin resistance [23].
However, the capacity of TG/HDL-C to predict insulin resistance may vary by race. For example, a study done in South Africa among overweight women that includes West Africa, Black South Africans and African Americans showed that the TG/HDL-C ratio was not predict insulin resistance [24]. On the other hand, studies in overweight women of Whites suggest that the TG/HDL-C ratio effectively identifies insulin resistance. Yet, the pattern of the dyslipidemia of insulin resistance differs in African Americans and Whites, and therefore the ability of the TG/HDL-C to predict insulin resistance may vary by race. In Whites, the dyslipidemia of insulin resistance follows the classic pattern of elevated TG and low HDL-C. However, in African Americans, West Africans and Black South Africans, normal TG with low HDL-C is the characteristic lipid profile of insulin resistance [25].
The mean values of TC and LDL-C were not show statistically significant differences between EFV and ATV/r-treated groups. However, the mean values of TC and LDL-C were slightly higher in EFV-treated group as compared to ATV/r-treated group. This is corroborated by the results of Ganesan et al. [18] and Squires et al. [17]. The higher TC in EFV-treated participants is likely due to both higher HDL-C and LDL-C values.
Similarly, it was found that both groups were not significantly different in the mean ratios of TC/HDL-C and LDL-C/HDL-C. In comparison to EFV, ATV/r-treated group was slightly higher in mean values of TC/HDL-C and LDL-C/HDL-C. Michael and Heneri [14] and Gotti et al. [26] also reported that both EFV and ATV/r-treated adult HIV patients were similar in mean ratios of TC/HDL-C. TC/HDL-C and LDL-C/HDL-C ratios are indicator of CVD risk with greater predictive value than isolated parameters used independently [27]. The predictive capacities of these ratios are supported by data suggesting that an increase in HDL-C is more prevalently associated with plaque regression. This may be particularly interesting in patients with features of the metabolic syndrome [28].
The current study had investigated the associations of some demographic, clinical features and anthropometric indices (BMI, WC, and waist-to-hip ratio) and lipid abnormalities in EFV- and ATV/r-treated group. Accordingly, CD4 count showed significantly positive association with serum TC levels among study participants on ATV/r-treated group. In agreement with the results of this study, Belay et al. [16] and Kamoru et al. [29] reported significantly positive correlation with CD4 among HAART patients. Waist circumference also significantly associated with TC among female participants in ATV/r-treated group. In agreement with these results, a study done by Beraldo et al. [30] reported significant association between waist circumference and TC levels.
An increased waist circumference is most likely associated with elevated risk factors of CVD because of its relation with visceral fat accumulation, and the mechanism may involve excess exposure of the liver to fatty acids and release of detrimental adipocytokines and lower levels of beneficial adipocytokines and these have multiple detrimental effects, including proinflammatory damage, altered signaling pathways and reactive oxygen species production, on beta cells and other tissues resulting in disease states like hypertension and diabetes [31].
Increased BMI showed significantly positive association with serum TC and LDL-C among female participants in the EFV-treated group. Importantly, anthropometric indicators in male participants were not significant determinants of any lipid variables in both groups. The reason behind this was unclear.
There was no statistically significant association observed between HDL-C and TG levels with predictor variables. Similar finding had been reported in studies conducted in London [32]. There was no association between duration of HIV positive since first diagnosis and duration on HAART and serum lipid parameters in both groups. These results agree with the study results of Nery et al. [33]. The observed difference between EFV and ATV/r-treated groups on associated factors of serum lipid levels was unknown.
Our study needs to be interpreted in the light of its limitations. The cross-sectional design precludes causal associations between dyslipidemia and patient characteristics. The study did not include a control group of HIV-uninfected persons which would have provided better insight into the role of HIV infection and antiretroviral drugs. There were baseline differences of the two groups on CD4 count, duration with HIV, duration on HAART and duration on current treatment so it may be affect the outcome variables.