ABSTRACT

1. Prevalence of Vitamin D Deficiency and Association with HIV Disease Progression in Females: Results from the Wings Clinic Women’s Cohort (WCWC) Study Johnson Britto1, Allen Griffin1, Lala Hussain1, Kelly Westhusing1, Alice Gunnison1, Diana Christensen1, Ruth Carrico1, and Forest Arnold1 1. Division of Infectious Diseases, University of Louisville ABSTRACT MATERIALS AND METHODS RESULTS CONCLUSIONS • Background: Deficiency in the level of vitamin D [25(OH)D] is associated with immune dysfunction. Patients with HIV infection and low vitamin D levels may be at risk for rapid progression of HIV disease. The objective of this study was to evaluate the natural progression of HIV disease in female patients with differing vitamin D levels. • Methods: This analysis was a retrospective observational study of adult HIV-infected women managed at the WINGS clinic in Louisville, KY, from 2006 to 2011. Demographic, laboratory, and treatment data, of eligible patients, were abstracted from medical records using a data abstraction form and entered into an electronic database for analysis. Patients were divided into three groups based on well accepted threshold for abnormal low levels of 25(OH)D: Group 1: severe vitamin D deficiency(<12ng/ml), Group 2:vitamin D insufficiency(12-20ng/ml), and Group 3:normal vitamin D levels (>20ng/ml). • Results: From a total of 164 medical records analyzed, baseline vitamin D levels were available in 127 patients. 18(14%) had 25(OH)D below 12ng/ml, 52(41%) between 12-20ng/ml and 57(45%) above 20ng/ml. 47(37%) were on Vitamin D therapy. Compared to those in Group 2(12-20 ng/ml) and Group 3(>20ng/ml), Group 1(<12 ng/ml) had a lower risk of immunological failure. HIV-infected women with severely deficient vitamin D levels (Group 1) who received vitamin D therapy showed consistent improvement in their CD4 levels in the subsequent years during the study period. The same was not true for women with insufficient (Group 2) and normal Vitamin D levels (Group 3). • Conclusions: In our cohort of HIV infected females, we saw inverse relationship between higher Vitamin D levels and median absolute CD4 counts. Rapid and aggressive supplementation of vitamin D in severely Vitamin D deficient patients may partially explain these results. The fact that a significant number of our population failed to have a normal vitamin D level highlights the importance of evaluating vitamin D levels in this population. .  • A total of 164 medical records of HIV-infected women were analyzed. Of these, baseline vitamin D levels were available for 127 patients. The earliest Vitamin D level obtained was in 2008. 18(14%) had 25(OH)D below 12ng/ml, 52(41%) between 12-20ng/ml and 57(45%) above 20 ng/ml. 47(37%) were on Vitamin D therapy. • Baseline characteristics of patients according to vitamin D status is shown in Table 1. • Trends of median CD4 count each year from Jan 2008 to December 2011 in relation to differing levels of Vitamin D levels is presented graphically in Figure 1. Compared to those in Group 2(12-20 ng/ml) and Group 3 (>20ng/ml), Group 1(<12 ng/ml) had a lower risk of immunological failure. • Figure 2 depicts median CD4 counts in patients receiving Vitamin D therapy. HIV-infected women with severely deficient vitamin D levels (<12ng/ml) who received vitamin D therapy showed consistent improvement in their CD4 levels in the subsequent years during the study period. The same was not true for women with insufficient(12-20ng/ml) and normal Vitamin D levels(>20ng/ml). • Higher median CD4 counts in severely Vitamin D deficient women can be due to aggressive treatment with Vitamin D. We need more data to further establish a time line measuring vitamin D deficiency and subsequent Vitamin D therapy improving CD4 count. • Although we saw inverse relationship between Vitamin D levels and median absolute CD4 counts over a period of 4 years, we cannot definitely conclude this finding because we do not have time related vitamin D levels available at follow up. • The fact that a significant number of our population failed to have a normal vitamin D level highlights the importance of evaluating vitamin D levels in this population. • Intervention studies on correction of vitamin D deficiency are warranted to gain a better understanding of the patho-physiological mechanisms behind these findings. Study Population and Setting: This analysis was a retrospective observational study of adult HIV-infected women managed at the Wings clinic in Louisville, KY, from 2006 to 2011. The Wings clinic cohort includes nearly 3,000 HIV-infected adults from Jefferson County, KY, as well as surrounding counties in Kentucky and Southern Indiana that are covered by public or private medical insurance. • Study definitions: Demographic, laboratory, and treatment data including – age, ethnicity, baseline 25(OH)D levels, HIV risk, CD4 count, antiretroviral therapy(cART), were abstracted from medical records and entered into electronic database for analysis. Patients were divided into three groups based on well accepted threshold for abnormal low levels of 25(OH)D. Group 1:severe vitamin D deficiency (<12ng/ml), Group 2:vitamin D insufficiency(12-20ng/ml), and Group 3:normal vitamin D levels(>20ng/ml). Median CD4 counts were used to estimate disease progression. • . Table 1. Baseline Characteristics of patients according to Vitamin D status LIMITATIONS Figure 1: Median CD4 counts of all patients according to their Vitamin D levels • A random sample of 164 HIV-infected patients is not large enough to estimate population parameters. Thus, the estimated prevalence of vitamin D deficiency, vitamin D therapy, and immunological response in this clinic population is imprecise. • Patients used Wings clinic as their usual source of HIV care for different lengths of time, thus were exposed to different amounts of lab draws, vitamin D therapy, and patient education on the need for screening and treatment. These factors may affect our actual findings. • The main limitation in this study is the observational design and the assessment of vitamin D levels exclusively at baseline. INTRODUCTION Decreased levels of vitamin D [25(OH)D] is common in the general population and it is associated with significant morbidity and mortality. Health conditions such as rickets, osteopenia, inflammation, cardiovascular disease, cancer, renal abnormalities, autoimmune diseases, and chronic infections have been associated with decreased levels of this vitamin. Vitamin D deficiency among HIV-infected patients may be more prevalent than in the general population due to HIV disease-related factors such as low sun exposure, poor intake and absorption, impaired hepatic and renal function, altered fat deposition, and interference of antiretroviral medications with vitamin D metabolism. In the last five years, numerous observational studies have suggested a high prevalence of vitamin D deficiency in HIV-infected patients and its detrimental effects on multiple health outcomes. There is evidence to suggest that vitamin D has regulatory effects on immune functions. The vitamin D receptor is expressed on adaptive and innate immune cells and vitamin D plays a role in innate immunity, particularly in the defense against chronic infections and in T cell activation. Thus, deficiency of vitamin D may lead to altered T cell proliferation further damaging the host defense system that is already compromised by the HIV infection. This may result in rapid progression of the disease in these individuals. Studies of vitamin D in HIV infected individuals have primarily included white men or have focused on young adults. We undertook this study to determine the prevalence and predictors of vitamin D deficiency among a cohort of ethnically diverse HIV-infected women in an urban outpatient HIV clinic. REFERENCES Figure 2: Median CD4 counts among patients receiving Vitamin D therapy according to their Vitamin D levels. Cervero et al: Prevalence of vitamin D deficiency: cross-sectional study of a hospital cohort of HIV-1 infected outpatients. Journal of the International AIDS Society 2010 13 (Suppl 4):P101. Giusti A, Penco G, Pioli G (2011) Vitamin D deficiency in HIV-infected patients: a systematic review Journal: Nutrition and Dietary Supplements Volume: 3 Issue: 1 Pages:101-111 Dao CN et al. Low vitamin D among HIV-infected adults: prevalence of and risk factors for low vitamin D levels in a cohort of HIV-infected adults and comparison to prevalence among adults in the US general population. Clin Infect Dis.2011 Feb; 52:396-405 Viard et al. Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study, AIDS: 19 June 2011 - Volume 25 - Issue 10 - p 1305–1315 Adeyemi OM, Agniel D, French AL, Tien PC, Weber K, Glesby MJ, Villacres MC, Sharma A, Merenstein D, Golub ET, Meyer W, Cohen M. J Acquir Immune DeficSyndr. 2011 Jul 1;57(3):197-204. *IVDU: intravenous drug use; cART: combined anti-retroviral therapy Statistical Analysis: Factors associated with 25(OH)D levels and associations of differing levels of 25(OH)D with immunological response measured by median CD4 counts and subsequent variation in median CD4 counts in response to vitamin D therapy were analyzed using Microsoft Excel 2010.