Influence of Folate Serum Concentration on Plasma Homocysteine Levels in HIV-Positive Patients Exposed to Protease Inhibitors Undergoing HAART

Abstract

Background: Homocysteinemia (Hcy) increase and risk factors in HIV-positive patients are not clear yet. Methods: HIV-positive patients on stable highly active antiretroviral therapy (HAART) regimens for at least 6 months were enrolled in this cross-sectional study. Among other factors, vitamin B₁₂, folate and length of exposure to protease inhibitors (PIs) were evaluated for their possible correlation with hyper-Hcy (>13 µmol/l in females; >15 µmol/l in males) by logistic regression analysis. Results: Ninety-eight HIV-positive patients were recruited. Twenty-eight (28.6%) had hyper-Hcy. Length of exposure to antiretroviral therapy and PIs did not result to be significantly associated with hyper-Hcy risk. Normal folate level was the only factor associated with the outcome, resulting protective from hyper-Hcy, either at univariate (OR = 0.22; CI 95% = 0.06–0.86; p = 0.029) and multivariable (OR = 0.24; CI 95% = 0.06–0.94; p = 0.04) logistic regression analysis. Folate predictive value of hyper-Hcy risk was driven by levels in the lowest quartiles of the study population (i.e. <10.9 nmol/l). Conclusions: No significant correlations were observed between hyper-Hcy and length of exposure to antiretroviral therapy or PIs. Folate could be a confounding factor in the association between hyper-Hcy and PI exposure found by others. The potential value of folate supplementation, in those who are deficient and in those with hyper-Hcy, merits study.

Elevated levels of vitamin B12 and folate in vertically infected children with HIV-1

“…Hyperhomocysteinemia has been reported in adults and children with HIV-infection and is directly correlated with folate deficiency [11,14]. It is reassuring to note that the median folate levels in our population were comparable to age-matched healthy children in the United States [15].…”

HIV-Positive Patients Respond to Dietary Supplementation with Cysteine or Glutamine

“…By refining the cutoff for males (>15 µmol/L) and females (>13 µmol/L), Uccelli et al [72] found a prevalence of 28.6% in a sample of 98 HIVpositive patients. However, no significant correlations were observed between HHcy and length of exposure to HAART.…”

“…However, no significant correlations were observed between HHcy and length of exposure to HAART. In two articles [71,72], the reduced availability of folate was raised as a confounding factor in the association between HHcy and ART. In fact, before the advent of HAART, 20% and 10% of HIV-infected patients had low vitamin B12 and red blood cell folate concentrations, respectively; now, the prevalence of low vitamin B12 is significantly lower in patients receiving HAART (8.7% versus 27%); 22.5% with low vitamin B12 and 51.4% with low folate had HHcy (>17.5 µmol/L).…”

Elevated homocysteine levels in human immunodeficiency virus-infected patients under antiretroviral therapy: A meta-analysis

“…Although the precise mechanisms by which HIV infection and ART affect Hcy metabolism are not known, the vitamin B12 and folate levels have been shown to affect Hcy levels in HIV-infected patients [23,50] . Specifically, Hcy levels are inversely related to the daily intake of folate and vitamin B12 in general population [20,21] .…”