The results of our study suggest that low HDL and hypertriglyceridemia were more commonly seen in HIV patients who died within a period of 3 months’ follow-up. The typical patterns of dyslipidemia seen in the HIV patients were low level of HDL, elevated TG, and raised TCH levels. In the study, besides low HDL and hypertriglyceridemia, M. tuberculosis
infection and low CD4 counts were the other variables associated with early mortality. The lipid abnormalities may be associated with insulin resistance and glucose intolerance in HIV patients.[10
] Evidence has established immune activation as a critical underlying mediator of immune dysfunction and immune deficiency in HIV disease.[9
] This state of immune activation is manifested both by enhanced expression of phenotypic activation markers on peripheral blood T cells and B cells and by increased plasma levels of inflammatory cytokines. Among the cytokines, the most consistent and potent inducers of HIV expressions are the pro-inflammatory cytokines: TNFα, IL—1, and IL-6.[13
] Dyslipidemia in HIV-infected/AIDS patients may occur even during the early stages of HIV infection and, more so as the disease progresses.[14
] Decrease in TCH and HDL cholesterol has been reported in the early stages of HIV infection, being more evident with decreasing CD4+ lymphocyte counts.[6
] Recently, efforts have been made to correlate acute phase reaction (APR) and lipid metabolism.[15
] Low HDL is associated with the presence of high plasma levels of IL-6, independent of the influence of a large number of possible confounders, including the main traits of the metabolic syndrome (triglycerides, fasting insulin, diabetes, hypertension, BMI, waist circumference), and lifestyle habits (smoking, alcohol intake, physical activity). The above mentioned conditions are frequently associated with significant modifications in both HDL and IL-6 plasma level.[16
] Interleukin 6, together with other cytokines, might influence HDL levels by modifying the activity of the triglyceride lipases. It has been shown that pro-inflammatory cytokines inhibit the activity of lipoprotein lipase[18
] and enhance the lipolytic activity of endothelial lipase.[19
] Both these actions have been associated with low HDL levels during acute or chronic inflammatory states. Unlike normal HDL particles, high-density lipoproteins modified by APR do not exhibit any in vitro
anti-inflammatory property. However, they are converted to pro-inflammatory molecules, perhaps as a consequence of their increased ceruloplasmin content.[21
] Dyslipidemia is also attributed to the use of non-nucleoside, nucleoside reverse transcriptase inhibitors, and protease inhibitors. Newer drugs, Raltegravir and Maraviroc, have proven not to be detrimental to the lipid profile.[22
In developing countries, patients report late, often in advanced stages of the disease, with a low CD4 count and a number of complications, including metabolic ones. We have observed that among the non-survivors the frequency of advanced stages of disease (AIDS) and OIs, particularly, M. tuberculosis
infection, and hypertriglyceridemia were significantly higher than survivors. Though the frequency of low HDL was higher in non-survivors, it was not significant. This might have attributed to the effect of other variables affecting the outcome in concert. Adjusted results showed that low HDL was an independent strong factor (P
<0.02) influencing the outcome. Surprisingly, in this study, low CD4 count (<200/mm3
) was not a strong predictor for short-term mortality. The reason would probably be the short follow-up period. Anemia has been widely reported to predict a poorer prognosis for HIV-infected patients, both in terms of progression to AIDS and in survival, independent of the CD4 lymphocyte count.[24
] In this study, anemia was not a significant predictor of survival; this is probably a result of the short follow-up time, and most of the patient were anemic. However, frequency of anemia was higher in non-survivors, but it was insignificant. Another important parameter is BMI measured at the time of diagnosis, which has been shown as a strong independent predictor of survival in HIV patients.[25
] Though the frequency of low BMI (<17.5 kg/m2
) was higher among non-survivors than survivors, it was also insignificant in our patients. The reason would probably be the short follow-up period.
Our study had some limitations such as the number of subjects was small, only hospitalized patients, who are usually very sick and have poor survival chances, were observed, only single time evaluation of lipid parameters was done, and all parameters could not be tested in all the patients. Moreover, the cause of mortality was not taken into account. In addition, no control group was considered.
The pathophysiology by which deranged metabolic parameters influence the poor short-term outcome in HIV disease, independent of other factors, is largely unknown. The probable mechanism being that in the presence of high IL-6 levels, HDL particles might be modified into pro-inflammatory molecules and thus maintain the inflammatory process in a kind of vicious circle. Advanced stages of the disease and heightened acute or chronic inflammation may be some of the contributing factors.
This undertaking may have an important implication that in resource-poor settings, CD4 counts, HIV viral load measurements, and established nonspecific serological markers of inflammation and/or coagulation such as IL-6, D—dimer, and high-sensitivity C-reactive protein are not always in place: Therefore, an algorithm using less sophisticated markers, such as serum HDL and TG levels, may be a useful adjunct for assessing disease progression and informing treatment and care.
Though the study has a few shortcomings, we would like to conclude that low HDL and hypertriglyceridemia are associated with increased short-term mortality in HIV disease, and it reinforces the notion that all patients who are being hospitalized should have a baseline evaluation of the said lipid parameters as well as should be monitored regularly, which would help in predicting their short-term mortality. Ours study was a pilot study; further work is needed, which would establish them as prognostic markers as well as markers of disease progression.