ARTICLE
Prevalence of dyslipidemias in antiretroviral therapy patients served in a specialized care service in Cuiabá (mt)

METHODS

This is a retrospective study including data collected from medical records of adult patients, of both genders, with HIV, followed-up at a SAE in the city of Cuiabá from January 2011 to August 2012.

The study included patients aged more than 18 years old, of both genders, undergoing ART and whose lipid profle was followed-up in the 12 months prior to the appointment.

For the collection of the informed data, an instrument composed of demographic, personal, anthropometric and biochemical data was used.

Based on biochemical tests, there were changes in total cholesterol (TC), total triglycerides (TT) and LDL, as well as a relationship with sociodemographic variables, stage of the disease, duration of treatment and type of medication.

The analysis of blood lipids used the reference values for the diagnosis of dyslipidemias in adults aged more than 20 years old, according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (2001) (Chart 1).

The stage of the disease was considered according to the CD4 count, using the values established by the Center for Disease Control and Prevention (CDC)⁽¹³⁾ (Chart 2).

Statistical analysis was conducted with the software Epi Info, version 3.6. Prevalence rates were compared using the qui-square test, considering a 95% confdence interval.

The study was in accordance with the rules established by the National Health Council (CNS) resolution. 196/96. The Ethics Research Committee of the University Hospital Júlio Müller approved it, report n. 08197212.7.0000.5541. The patients presenting changes in lipid profle were assisted at the Nutrition Service of SAE in the follow-up period.

With the study results, the expectation was to characterize the profle of patients assisted at the service, leading to the creation of a set of actions that would generate an improved health status of the participants.

RESULTS AND DISCUSSION

This study evaluated 124 individuals, being 56 (45.2%) female and 68 (54.8%) male participants. This is in agreement with the average in Brazil, whose ratio is 1.7 new case affecting men for one case affecting women⁽¹⁴⁾.

The most prevalent age group (50.8%) was 50 to 60 years old. The mean age of the patients involved in this study represents the cases of AIDS notifed in Brazil, as demonstrated by the Epidemiological Journal AIDS – DST in 2011. It shows that the highest proportion (24.8%) of AIDS cases notifed at the Notifable Diseases Information System (Sinan), declared in the Mortality Information System (SIM) and registered at the Medication Logistics Control System and the Viral Load Laboratory Tests Control System (Siscel/Siclom) in 2010 was present in the age group of 40 to 49 years old, with increasing incidence rates in the age groups of 50 to 59 years old and older than 60 between 1998 and 2010⁽¹⁴⁾.

In 2010, regarding the Center-West region, 31.0% of the total number of people notifed in Sinan had incomplete elementary school (between the 5^th and 8^th grades); 19.1% had incomplete or complete high school, and only 8.6% had complete or incomplete higher education (5.5% - complete). In 28.4% of the cases, this data was ignored⁽¹⁴⁾. Even though the percentage of patients who had incomplete elemnetary school was similar, those who got to higher education was higher.

As to origin, we observed that the highest percentage of patients comes from other states. This fact can be explained because we analyzed a reference service, or because our city is inhabited by people coming from other locations. The sociodemographic characterization of the patients is presented in Chart 3.

High prevalence of hypercholesterolemia (34.4%) and hypertriglyceridemia (69.7%) was found in the patients of this analysis. These data are in accordance with those mentioned in the IV Brazilian Guideline on Dyslipidemia and Prevention of Atherosclerosis⁽¹⁵⁾, which show that lipid abnormalities become more evident among people with HIV after the introduction of ART, and that hypercholestero-lemia and hypertriglyceridemia are the most remarkable disorders.

Farhi et al.⁽¹⁶⁾, in an investigation conducted with the objective of establishing the prevalence of dyslipidemia among adults of both genders with HIV, found a 44.7% prevalence of high blood TG. Hypercholesterolemia, which, in our study, was observed in 34.9% of the patients, is in accordance with the analysis by Leite & Sampaio⁽¹⁷⁾, which found a 35.0% prevalence of this change in patients undergoing ART assisted at a SAE unit in the city of Rio de Janeiro.

Regarding the time of exposure to an antiretroviral treatment, the prevalence of dyslipidemia was higher among patients who had been undergoing treatment for 1.0 to 4.9 years (44.2% of the cases); 45.5% had “very high” triglycerides, 41.7% had “high” cholesterol, and 80.0% had “very high” LDL, as shown in Table 1. Similar results were found by Falcão et al.⁽¹⁸⁾ in a cross-sectional study conducted in Pernambuco about cardiovascular disease and metabolic disorders in individuals with HIV. Of the 122 patients included in the study, 99 (81.1%) underwent ART with median and 3.3 years of therapy.

Farhi et al.⁽¹⁶⁾ showed that the mean time of ART use was longer among patients with changes in blood lipids (66.4 months versus 53.0 months), and this variable was positively associated with dyslipidemia.

As to the stage of the disease, there was a reduced number of patients with normal lipids when the condition got worse; however, the prevalence of “high” or “very high” blood lipids was higher among patients at the early stage, showing the onset of dyslipidemia even when patients still have a low viral load. Possibly, with the evolution of the disease, other factors may interfere in blood biochemistry (Table 2). However, when considering the initial and fnal means of TG and TC (Table 3), there is a statistically signifcant difference between results. This change shows that both the duration of treatment and the stage of the disease can lead to worse lipid profle.

A cross-sectional study conducted by Godoi et al.⁽¹⁹⁾, aiming at identifying the prevalence of atherosclerosis among individuals with HIV undergoing ART, showed that 84% of the patients evaluated had mean viral load of 670.6 (early stage). That is, when these patients present dyslipidemia (35.7% with hypercholesterolemia and 45.7% with hypertriglyceridemia) they are mostly clinically stable.

Both the infection with HIV and ART may cause or aggravate dyslipidemia. The acknowledged hypertriglyceridemia associated with the progression of the retroviral infection probably constitutes the refection of a chronic infammatory state or a consequence of emaciation⁽¹²⁾. According to Safrin & Grunfeld apud Seidl & Machado⁽²⁰⁾, the lipodystrophy syndrome (dyslipidemia, abnormal fat redistribution, changes in glycemic metabolism and insulin resistance) in seropositive people for HIV is a progressive condition, whose severity seems to be directly proportional to time of treatment with antiretroviral medication.

Advanced age and low T CD4+ cell count, associated with the beginning of ART, seem to be related to its development. Metabolic disfunction can also depend on age and on the genetic context of the individual, as well as on other environmental factors or concomitant medication⁽¹²⁾.

The beneft of a highly active antiretroviral therapy has been clearly demonstrated in patients with advanced symptomatic disease and in those who, despite being asymptomatic, presented severe immunodefciency expressed in the T-CD4+ lymphocyte count, below 200/mm³. Nowadays, in our country, there are four classes of antiretrovirals; they are more powerful, less toxic and with comfortable posology, so it is possible to take only one or two daily doses⁽²¹⁾.

This treatment, whose history began with the use of monotherapy with zivozudine (AZT), from 1994 to 1996, is now consolidated by the double therapy as a therapeutic pattern, and, after 1996, by the triple therapy, introducing the PIs⁽²²⁾.

Antiretroviral drugs work by blocking the action of enzymes, which are important for the replication and function of the HIV. The drugs should be used in standardized combinations. Montherapy is not recommended, due to the unavoidable resistance to medication⁽²³⁾. The action of each class of medication is exposed in Chart 4.

The initial therapy should always include three combined drugs: two nucleoside analog reverse transcriptase inhibitors (NtRTIs) associated with one non-nucleoside analog reverse transcriptase inhibitor (NNRTI) or with ritonavir-boosted PI (PI/r)⁽²⁰⁾. This practice has been used in SAE, where 29.3% of the patients in our study use the scheme “NNRTI + 2NtRTI”, and 22.8% use the scheme “NtRTI + PI”, as shown in Chart 5.

According to Godoi et al.⁽¹⁹⁾, among the antiretrovirals, PIs are more frequently associated with dyslipidemia and insulin resistance, even though medications from other classes, such as NtRTI and NNRTI, are present in metabolic disorders and in acute coronary events.

A major prospective and multinational study conducted with 17,852 patients registered the presence of hypercholesterolemia in 27% of the patients using PI, and 23% of those using NtRTI ⁽²⁴⁾. These fndings corroborate the data in our study, in which the highest prevalence of dyslipidemia was found in patients using the scheme NNRTI + 2NtRTI.

Even if less frequently than observed with PIs, NNRTI and NtRTIs also produce hypertriglyceridemia and increase the levels of TC and LDL cholesterol fraction⁽¹²⁾.

The mechanism in charge of inducing dyslipidemia among people with HIV is not completely clear yet. It is not clear if dyslipidemia occurs due to a direct effect of ART or if it is a result of the interaction between several factors, such as antiretroviral treatment, genetic predisposition, environmental factors like diet and physical activity, or other factors — possibly the response of the host to the HIV infection⁽²⁵⁾. However, regardless of the causing mechanism, the presence of dyslipidemia always requires the attention of health professionals, especially the nutritionist, who is essential to prevent and control blood lipids using an adequate diet therapy.

CONCLUSION

The use of antiretroviral therapy, which radically changed the treatment of patients infected with HIV, is associated with metabolic changes, such as dyslipidemia and insulin resistance, which constitute risk factors for the development of cardiovascular disease. The mechanism leading to dyslipidemia is not completely clear yet, so further ongoing studies are necessary.

Our investigation concluded that the risk of dyslipidemia increases with the duration of treatment, the severity of the disease and the type of drug used in therapy.

In order for the therapy not to cause any risk to the patient, changes in lifestyle, a balanced diet and physical activities should be implemented. The last resort for treatment would be pharmacological interventions.

It is also essential to raise awareness of the medical community for the increasing incidence of heart disease among patients with HIV undergoing antiretroviral therapy or not, once this incidence tends to grow because of the increasing life expectancy of infected patients.