Cardiovascular Risk Factors Among People Being Treated for HIV in Nepal: A Cross-Sectional Study

Antiretroviral therapy (ART) has rendered dramatic improvements in the life span and quality of life in patients infected with the Human Immunodeficiency Virus (HIV). However, several health risks and side-effects are found to be strongly associated with HIV and/or the use of ART ^{1, 2}, including cardiovascular-related complications ³. A number of observational studies have suggested that patients being treated for HIV are at elevated risk of cardiovascular diseases (CVD) ^{3, 4, 5}.Much of this elevated risk is thought to be mediated by dyslipidemia, clinical lipodystrophy, central obesity, insulin resistance, hypertension and kidney diseases ^{6, 7}. Furthermore, lifestyle choices which increase cardiovascular risk, such as tobacco usage, unhealthy diets, physical inactivity and drug abuse, are frequently observed among people living with HIV ^{8, 9, 10, 11, 12}.

The vast majority of previous studies of CVD among people with HIV were based in European, American and African settings, making it difficult to extrapolate findings to South Asia (which has distinct cultural, medical and lifestyle practices from other regions). Such lack of data from South Asia is in spite of rapid increases in the burden of CVD in the region ¹³, coupled with rapid increases in the usage of HIV treatments (reported to have increased 10 fold in the region in the past five years) ¹⁴.

Nepal is a developing South Asian country with a population of 30 million. Over 70,000 Nepalese people were living with HIV and AIDS in 2008 ¹⁵. Since the inception of ART services in Nepal in 2004, the number of HIV patients on ART has increased 60 fold in five years with 3834 Nepalese reported to be on ART in 2010 ¹⁶. Likewise, a high prevalence of cardiovascular-related risk factors (CVRF), mainly central obesity ¹⁷, hypertension ¹⁸, CKD ¹⁹, smokers and drinkers ²⁰ were observed in the general Nepalese population.With the backdrop of the increasing rate of CVD in Nepal ²¹, a high prevalence of CVRF and improved access to ART, the aim of this study was to assess the prevalence and distribution of selected CVRF among patients being treated for HIV in Nepal.

A total of 103 participants was included in this study, of whom 52 (50.5%) were men and 51 (49.5%) women from a variety of ethnic groups (Table 1). The median age of men and women was 38 years (interquartile range ^IQR 33,42), and 34 years (IQR 32, 39.5) respectively. Most of the participants were living in an urban area (64.0%), 16.5% were unemployed and 56.9% of the women and 15.4% of men had never attended school.

The median duration of HIV positive status and ART use was nearly two-fold in women as compared to men (Table 1). The median duration of HIV positive status was 24 months (IQR 3.5, 42.5) in women, but among men it was 12 months (IQR 3.7, 41.2). Women participants were receiving ART for 11 median months (IQR 1, 31.2), as compared to the six months (IQR 1, 32) for men. The median CD4+ count was 177 cells/mm³ (IQR 84.25, 260.25) in men, however it was slightly higher among women at 213.5 cells/mm³ (IQR 133.5, 348.5).

Regarding lifestyle factors, 66% (95% CI: 56.8% to 75.1%) of the participants had ever used tobacco products, 65% (95% CI: 55.7% to 74.3%) had ever smoked and 60.2% (95% CI: 50.7% to 69.6%) had ever consumed alcohol (Table 1). All of these three factors were extremely prevalent in males, and the differences in the proportion between males and females were statistically highly significant at <0.001 significance level. As regards relevant dietary intake in terms of cardiovascular risk, 88.3% (95% CI: 82.0% to 94.6%) of participants reported not attaining the recommended five portions of fruits and vegetables per day. Also, 27.2% (95% CI: 18.6% to 35.8%) of participants reported a high salt intake.

This is the first study in Nepal to document CVRF among the HIV population on ART. The key findings of this study are a high prevalence of central obesity, CKD and tachycardia. Risky lifestyle habits such as a high prevalence of smoking and alcohol consumption, especially in males and poor dietary habits (low fruit and vegetable and high salt intake) were also found. Overall, a third (34.6%) of the participants had central obesity and females had a disproportionately higher prevalence (60.0%) than the males (9.8%). This corroborates findings in larger studies, where the prevalence of central adiposity among HIV patients on HAART was 30% to 62% ³¹. Falutz suggested that factors such as female gender and treatment with antiretroviral drugs zidovudine (AZT) and efavirenz (EFV) may contribute to raise the risk of central adiposity ³². In our study, the vast majority of the participants (84.2%) were on AZT, EFV was also used by 24.2% and 17.9% were concurrently treated with both AZT and EFV along with other drug combinations. However, we could not demonstrate significant associations between HIV drug combinations and any of the CVRF. Due to the small sample size, we had to categorize nine drug combinations of the participants into two groups (duovir + nevirapine and remaining combinations) for analysis.

Very little research has been conducted in Nepal on central obesity based on W-H ratio and findings are hugely conflicting. In a study on healthy Nepalese males, central obesity was observed in 51.2% of the 1000 participants ¹⁷. By contrast, a recent study among 241 Nepalese men and women, found a prevalence of 2.5% in males and 10% in females ³³. The difference in cut-off values used to classify central obesity might have partly contributed to the difference in findings as Vaidya and colleagues ¹⁷ used a cut-off value of ≥0.95 for males and Adhikari and colleagues ³⁵ did not mention the cut-off point. Geographical and cultural differences of the study sites may also have played role in the variation. Nonetheless, the finding of a higher prevalence of central obesity in females may underpin the notion that abdominal lipohypertrophy is predominant in HIV treated females ³⁴, taking into consideration findings that South Asian populations, especially females, are more vulnerable to abdominal obesity ³⁵. This finding suggests the possible added risk of central obesity among HIV infected Nepalese females on ART.

The CKD prevalence in this study (20.7%) was the highest compared to other Asian studies conducted on HIV infected patients on ART - A Japanese study found 15.4% ³⁶ and a Chinese study found 16.8% prevalence of CKD ³⁷. Notably, the prevalence found was also higher than in the general Nepalese population, where Sharma and colleagues reported CKD in 14.4% of 8398 Nepalese adults ¹⁹. The methodological differences in defining CKD though should be noted (this study estimated eGFR using a Cockcroft-Gault formula, whereas Sharma and colleagues and the Chinese study followed the Modification of Diet in Renal Disease Equation (MDRD), and the Japanese study followed the equation suggested by Japanese Society of Nephrology).

Among the antiretroviral agents, Tenofovir disoproxil fumerate (TDF) has been found to be associated with increased renal dysfunction ³⁷, and the WHO has recognized it’s renal toxicity. However, in this study only two participants were being treated with TDF. This is an important factor for future studies as the use of TDF among the Nepalese HIV population is likely to increase rapidly in the future due to the recent guidelines of the WHO ³⁸ which recommends the reduction of stavudine (d4T) and use of TDF in a first line regimen. Stavudine is currently the dominant HIV drug in the Nepalese HIV population. Thus, clinicians and researchers should be more aware of renal health of HIV treated patients in Nepal.

Hypertension (systolic or diastolic) was found in 11.8% of the participants, which is significantly lower than the findings from other studies conducted in developed countries ^{39, 40}, but is similar to a study conducted in Africa (11.2%) ⁴¹. It is interesting to note that the prevalence found is also lower than that of the general Nepalese population of 19.7% to 33.9% ^{18, 42}. Several studies have demonstrated an association between hypertension and the duration of HAART. A large multi-centered study suggested a significant association after two years on HAART ⁴³, and an American study showed no association till six months ⁴⁴. In this study, the median duration of HAART use was eight months and could partly explain the lower rates. Larger studies are required to confirm the prevalence and aetiology of hypertension in the HIV treated Nepalese population.

Findings suggest that health education should target certain lifestyle habits i.e. smoking, alcohol consumption, diet and physical activity within the HIV treated Nepalese population to decrease their CVRF. The prevalence of smoking in this study was higher than in the general Nepalese population (current smokers: 46.6% vs. 23.8%) ²⁰, but is consistent with findings among other HIV+ populations ^{3, 45}. A propensity for smoking among people living with HIV could be due to its perceived role in emotional support and stress reduction ⁴⁶. Men especially should be targeted to educate them regarding the increased cardiovascular risk of smoking and other stress reduction therapies introduced.

In contrast, a considerably lower prevalence of current alcohol consumption was reported in the HIV infected participants than in the general Nepalese community (6.9% vs. 28.5%) ²⁰. This is also in contradiction to common trends found in studies conducted in developed countries ^{10, 47}. It is noteworthy that the prevalence of ever having consumed alcohol is higher though which could indicate that participants may have under-reported their alcohol consumption owing to social desirability bias or alternatively, due to the fact that two-thirds of the participants were poor, were not able to afford the high cost of alcohol. Alternatively, health education may have targeted this and resulted in a change in alcohol consumption habits.

As this was a cross-sectional study, a cause-effect relationship between CVRF and ART cannot be inferred. As participants were non-randomly selected and all based at one ART centre, the results shouldn’t be extrapolated to Nepal as a whole. Further limitations of self-reported responses could have introduced bias and restricted recorded biochemical measurements resulted in not being able to investigate the prevalence of other CVRF such as dyslipidaemia, clinical lipodystrophy and diabetes mellitus.

Although this was a cross-sectional study on a small sample, it provides important insights on the apparent risk of CVRF among HIV infected Nepalese patients on ART and warrants the need for further prospective and longitudinal studies.

This study provides important insights on the prevalence of CVRF among HIV infected Nepalese patients on ART, finding a high prevalence of central obesity, CKD and tachycardia as well as risky lifestyle habits. Not only does this warrant the need for further prospective and longitudinal studies, but it has implications for treatment and intervention within this population group. It also seems that health education messages should be gender-specific, with women being targeted with messages to avoid the risk of abdominal obesity and men regarding smoking and alcohol consumption as well as stress reduction therapy provided. Both groups should be educated about following a healthy diet and encouraged to continue doing physical activity. Finally, renal function should be monitored more closely if WHO guidelines are followed and TDF used more widely.

We are very grateful to Dr. Nadeem Sarwar, University Lecturer in Cardiovascular Epidemiology, University of Cambridge, UK for his significant contribution in study design, data collection and data analysis. We are grateful to the entire team of Teku ART centre, the research assistants (Amrit Bhandary, Bigyan Ojha, Bipin Thapa, Kreepa Bhattarai, Medha Sharma, Pratibha Dhungana, Seetu KC and Surendra Khanal) and the participants who consented to take part in the study.

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