Dyslipidemia in People Living with HIV on Anti-Retroviral Treatment: Case of the Ambulatory Treatment Center (ATC) of the Sylvanus Olympio University Hospital of Lome

Introduction: Dyslipidemia is a significant cardiovascular risk factor in patients living with HIV (PLWHIV). Few data are available in Togo. Objective: The purpose of this study is to assess the prevalence of dyslipidemia and associated factors in PLWHIV on Highly Active Antiretroviral Therapy (HAART). Methods: This is a descriptive and analytical cross-sectional study of patients followed at the Sylvanus Olympio University Hospital’s infectious diseases department for six months. The study population consisted of any PLWHIV patient on HAART over 18 years of age who had been regularly monitored and had a serum lipid fraction assay. Results: Two hundred and eighty-four dyslipidemia in patients on HAART as well as associated factors. To this end, it is necessary to insist on screening for dyslipidemia before and after initiation of HAART in order to prevent the occurrence of cardiovascular events in PLWHIV.


Introduction
The number of people living with HIV (PLWHIV) in 2017 was estimated to 36.9 million worldwide, of which 6.1 million live in West and Central Africa [1]. Increased access to antiretroviral treatment (HAART) has improved the care of PLWHIV.
The frequency of opportunistic infections has significantly decreased, improving patients' life expectancy. HIV infection has now become a chronic disease.
PLWHIV are now facing non-transmissible diseases linked to metabolic disorders such as dyslipidemia [2]. Dyslipidemia that leads to atherosclerosis [3] is recognized as risk factor for cardiovascular events alone or as part of a metabolic syndrome. PLWHIV are reported to be at greater risk of cardiovascular events than the general population [4].
According to some studies, depending on the current antiretroviral regimen, the prevalence of total hypercholesterolemia (HCT) in PLWHIV can reach 51% [5]. For hypertriglyceridemia (HTG), prevalences of up to 55% have been reported [6] while for HDL hypocholesterolemia (HCH) and for LDL hypercholesterolemia (HCL) prevalences of up to 43% and 47%, respectively, have been reported [6] [7]. The objective of our study is to study the prevalence of dyslipidemia in PLWHIV patients on HAART as well as associated risk factors in order to provide useful data for the care of these patients.

Presentation of the Study Site
Our study took place at the Ambulatory Treatment Center (ATC) of the Infectious Diseases Department of the Sylvanus Olympio University Hospital of Lomé (CHU-SO). This is the reference service for the care of PLWHIV in Togo. This service has an active line of 3528 patients, 70% of whom are women.

Type and Period of Study
We conducted a descriptive and analytical cross-sectional study on patients received in routine follow-up consultations during the period of July 1st to December 31st, 2018, a six months period.

Study Population
The study population consisted of all PLWHA on HAART over 18 years of age who had been regularly monitored for at least six months at the CTA of the CHU SO, having not missed any follow-up appointments in the six months pre- Any patient with a situation that could lead to an increase in abdominal volume and distort waist measurement (pregnant woman, liver pathology with ascites) or taking a treatment likely to disturb the lipid balance as a treatment with corticosteroid or lipid-lowering agent were excluded.

Sampling Method
We randomly selected for our study a sample of 284 patients who met the inclusion criteria.

Collection of Data
A data collection sheet was designed and used as a basis for data collection. Patients were informed in advance of the details of the data collection process. The data collected were: 1) socio-demographic data, age, sex; 2) history of pre-existing high blood pressure (hypertension) or ongoing antihypertensive treatment, the existence of known diabetes under treatment or not, a history of treated tuberculosis, alcohol consumption, active smoking 3) the history of HIV, namely the WHO clinical stage at initiation of treatment, the length of time spent on HAART, the CD4 count at initiation, the notion of substitution of combinations during HAART, the current ARV protocol; 4) anthropometric data such as weight, height, body mass index, waist circumference; 5) data from analyses of TxCD4 monitoring, CT, TG, HDL-c assays. LDL-c was calculated from the Friedwald formula according to the formula: LDL-c = CT − (HDL-c + TG/5).

Data Sources
Age, sex, notions of hypertension and diabetes, history of HIV, were collected by interview and via the care record.
The weight was measured using a weighting scale. The height was measured using a measuring tape. The body mass index (BMI) was calculated using the ra-

Statistical Analysis of Data
All data were entered into an input mask developed in the epi data version 3.1 software and then analyzed using the IBM SPSS Statistics 20 statistical software.
The descriptive analysis included means and standard deviations, medians and interquartile range for quantitative variables. Percentages were used for qualitative data.
The differences between the means and percentages were assessed using the Student's t-test for quantitative variables, and the chi-square test for qualitative variables.
The test results were considered statistically significant if the p-value < 0.05.

Ethical Considerations
The authorization of the head of Infectious Diseases Department in charge of the Ambulatory Treatment Center for HIV-infected persons has been obtained. The written consent of patients was obtained after an informed explanation of the objectives of the study. Anonymity and confidentiality of the results were respected.

General Characteristics of the Study Population
A total of 284 patients were enrolled in our study. Eight point eight percent of the patients in our sample had a past history of treated tuberculosis (TB). Two point five percent of patients were known to be diabetic and 13% were known hypertensives. Thirteen point one percent of the patients in our series reported being alcohol consumers. Three point nine percent of the subjects had a smoking history. Fifty-seven percent of the subjects had already seen their HAART combination substituted at least once. Eighty-two point seven percent of the patients in our sample were on 1st line HAART and 17.3% on 2nd line HAART. At the initiation of treatment, 63.3% of patients were in WHO clinical stages 2 and 3. The median duration under ART was 4.18 years (IQR: 2 -7). Fifty-nine point three percent of the patients in our sample had been under HAART for less than five years.
The median body mass index was 23.80 kg/m 2 (IQR: 21.05 -27.05). Forty point eight percent of patients in our study had BMI of 25 kg/m 2 or greater.
The average waist circumference was 86 cm (±10.5). High waist circumference defined abdominal obesity was present in 55.8% of patients.

Lipid Profiles of Patients
Dyslipidemia were found in 72.5% of cases. The prevalence of each type of dyslipidemia was 49.6% for HCH, 32.7% for HCL, 30.6% for HCT and 10.9% for HTG ( Figure 1). Fourteen point height percent of the subjects in our study had a CT/HDL ratio greater than 5.   The study of the associations between dyslipidemia and the HAART molecules to which the subjects in our study were exposed revealed a statistically significant association between the NRTIs and the HCH ( Table 2).
A CT/HDL-c ratio was associated with HCL (p < 0.001). (Table 4)     Factors associated with HTG Our study did not identify any factors significantly associated with the occurrence of HTG (Table 6).

Discussion
The purpose of our study was to evaluate the prevalence of dyslipidemia in PLWHIV subject on HAART at CTA, CHU-SO Lomé. The pre-therapeutic check-up that is requested of patients before initiation in our context does not require a lipid check-up to assess dyslipidemia in newly diagnosed HIV-positive patients before HAART begins. It was therefore impossible for us to profile dyslipidemia in patients before HAART is initiated. Indeed, it is not excluded that some patients may develop dyslipidemia before HAART is initiated according to the chronic inflammation due to the HIV or according to the genetic predispositions. However, our study allowed us to highlight an overall prevalence of dyslipidemia at 72.5%. This result is similar to those reported in Cameroon and Tanzania [9] [10] but lower than the 82.3% reported in southern Ethiopia [6].
The prevalence of different dyslipidemia in our study was 49.6%, 32.7%, 30.6% and 10.9% respectively for HCH, HCL, HCT, and HTG. The CT/HDL ratio indicated a high risk of atherosclerosis in 14.8%.
Our prevalence of HCT is similar to that reported in Cameroon by Bekolo et al. [9]. Nevertheless, other authors have achieved higher rates of 41% according to a study conducted in Togo by Djibril et al. [11] while in Uganda Buchacz et al.
The prevalence of HTG observed in our study is lower than data reported by other authors who give a prevalence of HTG ranging from 18.3% reported in Benin by Adebayo et al. [13] to 55.8% reported in Ethiopia by Tadewos et al. [6].
We have achieved an HCL prevalence of 32.7%. This prevalence is in line with the work of Bekolo et al. in Cameroon [9], de Tadewos et al. in Ethiopia [6], and Adebayo et al. in Benin [13], which reported 33.3%, 33.6% and 34.83% respectively. However, Armstrong et al. in Tanzania found in their series a 12% lower Open Journal of Internal Medicine prevalence [10].
HCH was found in 49.6% of the subjects in our study. This result confirms the one reported by Ezra et al. in Ethiopia [14], de Bernal et al. [15] in Spain, and Buchaz et al. in Uganda [12]. Nevertheless, a lower prevalence of 18.4% was reported by Bekolo et al. [9] and a higher prevalence of 43.4% by Tadewos et al. [6].
Fourteen point eight percent of the patients in our sample had a CT/HDL ratio at high risk of atherosclerosis. This result is close to those observed in Cameroon [5] [9]. In Ethiopia, a 45.5% higher rate of patients on HAART with a high risk of atherosclerosis has been reported [6].
HCH was the most common dyslipidemia in our series followed by HCL ( Figure 1). There is high variability in the literature with respect to the forms of dyslipidemia that predominate in PLWHIV under HAART.
Some studies reported HTG and HCL as the most predominant dyslipidemia [7] [9] while for others it was HTG and HCH [16].
This variability in dyslipidemia in PLWHA under HAART could be explained by multiple factors, namely HIV-induced inflammatory stress, individual genetic susceptibilities such as sex, gender and ethnicity [17]. Studies have also shown that the metabolism of antiretroviral drugs plays an important role in the high variability between individuals exposed to the same antiretrovirals [18].
The age groups 30 to 39 and 40 to 49 were the most represented with 61.6%, which is consistent with the results of Djibril et al. [11].
The median body mass index was in our series of 23.80 kg/m 2 (IQR: 21.05 -27.05). This result is very close to the median reported in Tanzania [10]. 40.8% of the subjects in our sample had a BMI greater than or equal to 25 kg/m 2 , of which 29.2% were classified as overweight and 11.6% as obese. Our result is close to what was observed by Djibril et al. in Togo [11] who observed in its series 36% but higher than the 20.4% reported by Tadewo et al. in southern Ethiopia [6].
Abdominal obesity was present in 44.2%. This result is similar to the one observed by Adébayo et al. who found in his series 51.23% [13].
There was no significant difference in dyslipidemia frequencies depending on whether the patient was on an NNRTI-based or PI-based combination. Djibril [13]. HCT is associated to HCL. This indicates a predisposition in PLWHIV to develop atheroma plaques and therefore a high susceptibility to cardiovascular events. This trend is confirmed by the association between HCL and a CT/HDL ratio greater than 5. We found that BMI was associated with HCH. Adebayo achieved the same result as Armstrong [10] [13].
Beyond the undernutrition that can accompany HIV infection and explain HCH, many studies argue in favor of a disturbed HDL-c metabolism in PLWHIV compared to uninfected subjects. This may explain the low level of HDL-c frequently observed in PLWHIV [28]. After initiation of HAART, lipid levels return to normal levels and then increase well beyond pre-seroconversion levels except for HDL-c which persist at low levels [29] [30].
HCT was associated with HCH. HDL-c being a protective factor, this result indicates in PLWHIV a higher risk of atherosclerosis, confirming the data in the literature that the incidence of cardiovascular events may be higher in PLWHIV than in HIV-negative subjects.
In our study, being female increased the risk of HCH. This result contrasts with the findings of Armstrong et al. who found no association of HCH by gender [10]. Abdominal obesity (p = 0.029) was in our series associated with HCH. Obesity is closely linked to hypertension, diabetes, and dyslipidemia. Abdominal obesity and HCH fall within the definition of metabolic syndrome. Obesity is an independent risk factor for cardiovascular disease and is associated with a high risk of mortality [31].
Smoking was in our study associated with HCH. This is consistent with data in the literature that have shown an association between smoking and HCH and how smoking cessation contributes to an increase in HDL-c [32] [33].
Other risk factors associated with HCH such as age, CD4 count, viral load, HTG reported in some studies were not identified in our study [10] [15].
Our study showed that HCT, HCH and HCL significantly increased the risk of atherosclerosis in PLWHIV on HAART because they were associated with a CT/HDL ratio greater than 5 and therefore an increased risk of cardiovascular events. The international D:A:D (Data collection on adverse events of anti-HIV drugs) study showed a relative annual increase of 26% in the rate of myocardial infarction in patients exposed to HAART compared to the incidence in HIV patients not exposed to HAART [34].

Conclusions
Our study showed a high prevalence of dyslipidemia in patients receiving antiretroviral treatments at CTA, indicating a high risk for these patients to have cardiovascular events that could shorten their life expectancy.
Therefore, emphasis should be placed on screening for dyslipidemia for its care not only during the follow-up of patients on antiretrovirals but also before initiation of HAART.

Conflicts of Interest
We announce that we have no competing interests.