Serum Retinol and HIV-1 RNA Viral Load in Rapid and Slow Progressors

Abstract

Few studies have addressed the relation between serum vitamin A level and HIV disease progression. Thirty HIV-infected women in Rwanda were studied over a time span of 26 to 99 months. Fourteen subjects seroconverted and died of HIV-related disease at a mean of 44 months (range, 26-69 months) after their first HIV-positive test and were termed "rapid progressors," (RPs). A comparison group of 16 "slow progressors" (SPs) were HIV-positive at the time of their first HIV serology and had asymptomatic HIV infections at a mean of 96 months (range, 93-99 months) after their first HIV serology. Baseline mean serum retinol values were the same in RPs and SPs: 0.65 + 0.08 mmol/L versus 0.67 + 0.09 micromol/L (p = .7). Lower serum retinol levels were observed in RPs compared with SPs for the second and third measurements, obtained at a median of 12 and 24 months past baseline: 0.51 + 0.07 mmol/L versus 0.76 + 0.14 mmol/L (p = .3) and 0.44 + 0.09 mmol/L versus 0.64 + 0.08 mmol/L (p = .08), respectively. Median retinol levels for the third sample measurement were similar in RPs with lower viral load (LVL) and SPs (0.49 mmol/L and 0.52 mmol/L, respectively) compared with only 0.19 mmol/L in RPs with higher viral load (HVL; p = .02). A trend toward decreasing serum retinol levels and increasing HIV-1 RNA viral load was observed at the third sample measurement (p = .04). Subjects with LVL, higher serum retinol levels (> or =0.70 mmol/L), or both had more favorable rates of survival than subjects with HVL, low serum retinol levels (<0.70 mmol/L), or both. Although sample size does not permit definitive conclusions, this study demonstrates an association of high HIV load, rapid progression, and low serum retinol late but not early in disease progression.

Retinoid-Dependent Restriction of Human Immunodeficiency Virus Type 1 Replication in Monocytes/Macrophages

“…This may help to explain why HIV-1 expression in macrophages increases at later stages of disease (35). In vivo, HIV-1 infection often leads to vitamin A deficiency at times when the levels of virus production increase (2,9,29,44,59). The loss of retinoid-mediated repression may account, in part, for the increased levels of HIV-1 replication seen at later stages of disease.…”

“…Latently infected T cells and macrophages may avoid recognition by virus-specific CTLs and act as potential reservoirs for the dissemination of HIV-1 at later stages of disease. Vitamin A regulation is often impaired concomitant with progression toward AIDS, resulting in vitamin A defi-ciency (2,9,29,44,59). This deficiency may result in the loss of RA-mediated repression of HIV-1 and may contribute to viral expansion and progression toward AIDS.…”

A Longitudinal Study of Neutralizing Antibodies and Disease Progression in HIV‐1–Infected Subjects

“…The first is a significant decrease in the level of NAbs in the sera of the RPs. This cannot be attributed to a lack of immunogen, since increases in viral load are associated with progression to AIDS [26,27]. The decreased Ab levels are undoubtedly caused by the general deterioration of the immune response of the RPs, which has been well-documented not only in terms of decreased Ab titers, lower immunoglobulin levels, and decreased CD4 ϩ counts [2,28], but also in increased CD4 ϩ and B cell apoptosis [29], decreased antibody-dependent cellular cytotoxicity (ADCC) [30], and decreased proliferative responses [31].…”

Rapid Disease Progression in Human Immunodeficiency Virus Type 1-Infected Seroconverters in India

“…1,2 Possible explanations suggested include lack of access to health care, 3 coinfection with other pathogens, 4 malnutrition, 5 and other endemic infections before development of severe immunodeficiency. 6 A large number of studies from the United States and Europe have demonstrated that plasma HIV RNA copies (viral load) measurements and CD4 counts are highly predictive of clinical progression to AIDS 7,8 and the rate of clinical progression may depend upon early postinfection immunological and virological events.…”