Page 169 - AIDSBK23C

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syndrome, since the degree of weight loss correlates with increasing HIV-1 RNA levels and with
decreasing CD4 lymphocyte counts.[725]
Decreased oral intake of food is also a very important etiology for weight loss in HIV
infection and highlights the need for good nutrition. Good nutrition may be needed to counteract
the effects of malabsorption that can contribute to wasting syndrome. Sometimes a specific
intestinal pathogen can be identified, but not in all cases. Up to half of HIV-infected patients
may have abnormal d-xylose absorption tests.[725]
Varieties of therapies have been utilized to counteract wasting syndrome. These include
the use of megestrol acetate as an appetite stimulant, thalidomide as a cytokine inhibitor, and
recombinant human growth hormone or testosterone as anabolic agents. Controlling diarrhea,
nausea, and fever as well as providing nutritional support can diminish the impact of wasting
syndrome.[725]
In the U.S., HIV wasting syndrome alone as an indicator disease once accounted for up to
7% of all newly reported AIDS cases, and was reported along with additional indicator diseases
in another 10% of cases. In a large study in the U.S., the incidence of wasting syndrome
declined from 1992 through 1999, with the most marked rate of decline occurring after 1995.
The incidence of AIDS and non-AIDS-defining illnesses was generally high at or after a
diagnosis of wasting syndrome. Factors significantly associated with improved survival included
a CD4+ count of ≥200 cells/µL during the interval of the wasting syndrome diagnosis and
antiretroviral therapy with two or more drugs at or after the diagnosis of wasting syndrome.[726]

HIV LIPODYSTROPHY.-- Persons with HIV infection may develop lipodystrophy
(lipoatrophy) with lipid abnormalities, insulin resistance, and lactic acidosis. Half of HIV-
infected persons receiving antiretroviral therapy (ART) may have one or more features of
lipodystrophy. The term protease inhibitor-associated lipodystrophy (PIAL) has been employed
with a protease inhibitor is part of ART. Despite the abdominal distension, there may be a
normal to decreased body mass index. [269] Lipodystrophy, however, appears to be associated
with multiple ART regimens and not specific drugs.[727]
The mechanisms for PIAL are not known, but may be related to a number of factors. The

nucleoside analogues most associated with lipoatrophy are zalcitabine, didanosineand stavudine,
due to toxicity towards mitochondria. The protease inhibitors (PIs) may alter pro-inflammatory
cytokines such as TNF-alpha and IL-6 and lead to increased adipocyte apoptosis, reduced lipid
accumulation in adipocytes, and reduced insulin-stimulated GLUT-4 mediated glucose uptake.

Of the PIs lopinavir, ritonavir, saquinavir and nelfinavir are theworst. Inhibition of the sterol
regulatory enhancer-binding protein 1 (SREBP-1) that mediates activation of adipocyte retinoid
X receptor and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) can
occur.[728]
There is evidence that an adipocytokine, adiponectin, a protein product of the apM1 gene,
which is expressed exclusively in adipocytes, plays a role in development of lipodystrophy with
HIV infection. In vitro and animal studies and cross-sectional studies in humans have shown that
adiponectin is inversely correlated with features of this metabolic syndrome including obesity,
insulin resistance, type 2 diabetes, and coronary heart disease, as well as congenital and acquired
lipodystrophies in non-HIV infected subjects. Thiazolidinediones that act as agonists for the
nuclear receptor transcription factor PPAR-gamma, a subtype of the nuclear receptor superfamily
found in adipose tissue, influence the expression of genes involved in adipocyte differentiation,