RESEARCH INTEREST: HIV TREATMENT OUTCOMES IN ADULTS WITH PARTICULAR INTEREST ON CARDIOVASCULAR RISK ASSESSMENT

TITLE:  CARDIOVASCULAR RISK ASSESSMENT AMONG HIV INFECTED PERSONS ON TREATMENT WITH ANTI RETROVIRAL DRUGS IN JOS, NIGERIA

ABSTRACT:

Non communicable diseases (NCDs) are reported to be among the leading causes of morbidity and mortality in the developed as well as developing world. With the advent of treatment with highly active anti-retroviral therapy (HAART), significant improvement in life expectancy has resulted in increasing numbers of HIV-infected persons developing chronic conditions like cardiovascular diseases. This increased burden of cardiovascular disease among HIV-infected persons have been attributed to factors related to the disease like chronic inflammation from the virus, side effects of treatment with HAART as well as the established risk factors for developing cardiovascular disease in the general population among others.

The burden of cardiovascular disease risk in persons living with HIV/AIDS in our environment is unknown.

We hypothesize that HIV infected persons on treatment with HAART are not at an increased risk of cardiovascular disease. This study aims to determine the prevalence and predictors of cardiovascular disease in a cross sectional study as well as assess the risk of developing cardiovascular events among HIV patients on HAART.

BUDGET

Expenditure category	Unit cost (N)	Total cost (N)
Research assistant	15,000	180,000.00
Laboratory tests	Urinalysis: 200x250=50,000 Total cholesterol:1000x250x3=750,000 HDL:500x250x3=375,000 Serum creatinine:500x250x3=375,000 Haemoglobin:400x250x3=300,000 CD4 count: to be obtained from APIN database Viral load: to be obtained from APIN database	1,850,000.00
Internet and Communication	5,000	60,000.00
Publication cost	100,000	100,000.00
Total cost		N2,190,000.00

 

Budget justification:

Research assistant: Shall have 100% effort on the research and be paid monthly salary during the study. He or She shall also receive stipends as communication support with research team and with participants for scheduling follow up visits.

Lab tests:

Urinalysis at recruitment

Total cholesterol, HDL, haemoglobin and serum creatinine at recruitment, 6 months and at 12 months

Internet data and communication:  for access to online cardiovascular risk assessment tools, for follow up contact of participants.

Publication: For dissemination of research findings in high impact journals

PROJECT NARRATIVE

When the grant is awarded, this research will provide data which will be invaluable in future grant application. It will provide experience in conducting research and when the data is well disseminated it would attract external collaborators for future research works.

RESEARCH PLAN

GENERAL AIM: To assess the cardiovascular risk among HIV patients on HAART

SPECIFIC AIMS

1. To determine the prevalence of cardiovascular risk factors among HIV patients on HAART
2. To determine the association between cardiovascular risk factors and scores (Framingham. D:A:D and EURO sida/ Death) and CD4 count
3. To determine the association between cardiovascular risk factors and scores (Framingham. D:A:D and EURO sida/ Death) and viral load

BACKGROUND AND SIGNIFICANCE

Non communicable diseases (NCDs) are reported to be among the leading causes of morbidity and mortality in the developed world.  In the developing world, it is also feared that NCDs contribute to significant morbidity and mortality alongside the burden of communicable diseases thus placing individuals in the developing world under the so called "double whammy" of disease burden.¹ Additionally, sub-Saharan Africa with a total population of less than 15% of the world's population bears about 70% of the HIV/AIDS burden and 74% of AIDS related deaths.²  With the advent of treatment with highly active anti-retroviral therapy (HAART), significant improvement in life expectancy has resulted in increasing numbers of HIV-infected persons developing chronic conditions like cardiovascular diseases. This increased burden of cardiovascular disease among HIV-infected persons have been attributed to factors related to the disease like chronic inflammation from the virus, side effects of treatment with HAART as well as the established risk factors for developing cardiovascular disease in the general population among others. It is also known that traditional and HIV specific cardiovascular risk factors combined with HAART related metabolic complications, increase cardiovascular disease risk 1.5 to 2 fold in HIV infected compared to HIV uninfected patients.³

Cardiovascular disease risk in HIV has been studied in many patient populations.^4,5 However only few of these studies have been conducted on indigenous Africans.^6,7  It is therefore unknown the burden of cardiovascular disease risk in persons living with HIV/AIDS in our environment as assessment for developing cardiovascular disease is not routinely done.

We hypothesize that HIV infected persons on treatment with HAART are not at an increased risk of cardiovascular disease. This study aims to determine the prevalence and predictors of cardiovascular disease in a cross sectional study as well as assess the risk of developing cardiovascular events among HIV patients on HAART.

METHODS

Study design and location

This will be a cross sectional descriptive study involving adult HIV patients on HAART using a non probability sampling technique will be used to recruit every consecutive participant until the minimum sample size is met. Participants will also be followed up every 6 months to the end of the study period (one year). This study will be carried out at the APIN-supported Adult HIV clinic at JUTH. This clinic is located in the urban city of Jos, Plateau state and serves a population of over 22million people from Plateau and the neighboring North central states of Nigeria. The clinic commenced HIV services in 2002, and has cumulatively enrolled over 23,000 adults for HIV care and treatment with over 12,000 on follow up.⁸

The risk factors to be studied include the traditional cardiovascular risk factors like obesity, hypetension, diabetes mellitus and dyslipidaemia while HIV specific risks like duration on HAART, HAART combination as well as levels of immunity and viraemia will be studied. Participants will be followed up to determine the development of primary and secondary end points. The primary end points for this study is all cause mortality or a change in cardiovascular risk score while the secondary end points include doubling of serum creatinine or halving of estimated glomerular filtration rate as well as hospitalisation for heart failure, stroke or myocardial infarction.

Sample size determination

The sample size would be determined using the Bennett formula⁹

            N   =     z²pq

                            d²

Where N = minimum sample size

p = prevalence of the highest cardiovascular risk factor among HIV patients on HAART in a study by Muhammad et al¹⁰ at 17%

 d = level of precision taken as 5%

z = standard normal deviation at 95% confidence interval which is (1.96)²=3.84

q= 1-p

Therefore,             

                       

 N = 3.84 x 0.17 x 0.83     

                                         0.05²

                                      

                                     =216

This number will however be raised to 250, allowing for 10% attrition.

 

Inclusion and exclusion criteria

 All adult patients with: 1.HIV on HAART who are 18 years and above, and 2.Who consent to the study will be enrolled. Exclusion criteria include: 1.Adult patients with HIV but not on HAART.  2. Those that do not consent to the study, and 3. Pregnant HIV positive patients.

Data collection

 A structured questionnaire will be administered to assess for cardiovascular risk factors from history. Information to be obtained will include: age, sex, duration on HAART, HAART regimen, as well as history of diabetes mellitus and hypertension.

 Clinical examination will be performed on each participant for anthropometric and blood pressure measurements. Weight will be recorded in kilograms to the nearest 0.1kg using a flat scale on a firm horizontal surface with subjects wearing only light clothes and without shoes and headgears. Height will be measured without shoes, caps or headgears with subjects standing erect on a stadiometer. Measurements will be taken to the nearest 0.01 metres. The body mass index (BMI) will be calculated from weight in kilograms (kg) divided by the square of the height in metres squared (m²). Additionally, waist and hip circumference will be measured using a non elastic tape.

Blood pressure (BP) will be taken after five minutes of rest using a mercury sphygmomanometer in a sitting position with arm at level of heart. Systolic BP will be recorded at phase one of Korotkoff sound and diastolic BP at phase five. Three readings will be taken while the average of the best two readings will be recorded.

 Laboratory investigations to be done will include urine collection for urinalysis.10mls of venous blood will be taken for the determination of total cholesterol, high density lipoprotein (HDL), serum creatinine, and haemoglobin levels. All laboratory tests will be done using standard biochemical methods. A repeat blood collection will be done after every six months as part of follow up till the end of the study (a total of 3 blood collections)

Statistical analysis

 Statistical analysis will be done to determine the relationship between traditional cardiovascular risk factors like hypertension, diabetes mellitus, smoking and dyslipidaemia and HIV related factors like duration on HAART, CD4 count, viral load and type of ARV combination. Risk assessment for patients using the Framingham, D:A:D and the EURO sida/ Death risk scores will be carried out using online tools.

Data will be analysed using Epi info version 7.2.0.1, CDC, Atlanta Georgia statistical software. Continuous variables with normal distribution will be expressed as means ± SD while median and inter quartile range will be used for skewed distributions. Categorical variables will be expressed as proportions. The Chi-square test will be used to determine the association between categorical variables. The Student “t” test would be used to compare group means. Multivariate analysis would be used to identify cardiovascular risk factors that are independently associated with CD4 count and viral load respectively. A p value ≤ 0.05 will be considered significant.

Plan for Protection of Human Subjects

A written informed consent would be obtained from the patients. Patients with limited understanding of English would be adequately informed on the study in the language they understand best. The benefits to the patients will include assessment of their cardiovascular risk profile, health education, counseling and referral for further care if the need arises. Participation will be voluntary. Participants are at liberty to withdraw their consent at any time during the study and refusal to participate will have no effect on the access to care of such an individual. All information provided will be treated with utmost confidentiality. Data would be de-identified and coded; the codes would be separately and securely stored from the main data.

Pending IRB Approval

Ethical clearance for the study will be obtained from the Ethics Committee of the Jos University Teaching Hospital before the commencement of this study

REFERENCES

1.        WHO. Global status report on noncommunicable diseases 2014. World Health. 2014:176. doi:ISBN 9789241564854.

2.        Kharsany ABM, Karim QA. HIV Infection and AIDS in Sub-Saharan Africa: Current Status, Challenges and Opportunities. Open AIDS J. 2016;10:34-48. doi:10.2174/1874613601610010034.

3.        Krikke M, Hoogeveen RC, Hoepelman AIM et al. Cardiovascular risk prediction in HIV infected patients:Comparing the Framingham, Atherosclerotic Cardiovascular disease risk score (ASCVD), Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) risk prediction models.HIV Medicine 2016;17(4):289-297

4.        Okeke NL, Davy T, Eron JJ, Napravnik S. Hypertension Among HIV-infected Patients in Clinical Care, 1996-2013. Clin Infect Dis. 2016;63(2):242-24.8. doi:10.1093/cid/ciw223.

5.        Koganti S, Kinloch-de Loes S, Hutchinson S, Johnson M, Rakhit RD. Management of cardiovascular conditions in a cohort of patients with HIV: experience from a joint HIV/cardiology clinic. Clin Med. 2015;15(5):442-446. doi:10.7861/clinmedicine.15-5-442.

6.        Mashinya F, Alberts M, Van Geertruyden J-P, Colebunders R. Assessment of cardiovascular risk factors in people with HIV infection treated with ART in rural South Africa: a cross sectional study. AIDS Res Ther. 2015;12:42. doi:10.1186/s12981-015-0083-6.

7.        Osegbe ID, Soriyan OO, Ogbenna AA, Okpara HC, Azinge EC. Risk factors and assessment for cardiovascular disease among HIV-positive patients attending a Nigerian tertiary hospital. Pan Afr Med J. 2016;23:206. doi:10.11604/pamj.2016.23.206.7041.

8.        Norma CW, Monique AW, Elvin HG, Kaaya FS, Agbaji OO, Muyindike WR et al. Toward an understanding of disenegagement from HIV Treatment and Care in Subsaharan Africa: A qualitative Study. PLoS Med. 2013;10:e1001369. doi: 10.1371.

9.        Bruce N, Pope D, Stanistreet D. Quantitative Methods for Health Research: a practical interactive guide to epidemiology and statistics. John Wiley & Sons Ltd. 2008; 133-145

10.      Muhammad S, Sani MU, Okeahialam BN. Cardiovascular disease risk fac- tors among HIV-infected Nigerians receiving highly active antiretroviral therapy. Niger Med J. 2013;54(3):185–90.