The introduction of highly active antiretroviral therapy (HAART) around 1996 markedly reduced mortality and morbidity from human immunodeficiency virus (HIV) infection. As life expectancy has improved, the chronic complications of HIV and HAART have become increasingly relevant.
This article provides an overview of the HIV-associated lipodystrophy, its pathogenesis and its clinical consequences (based on a search strategy in PubMed including literature published to November 2007).
Lipodystrophy syndrome is characterized by abnormal fat distribution syndrome associated with metabolic disturbances and includes insulin resistance, deranged glucose and lipid metabolism. It is associated with increased risks of progression to type 2 diabetes and cardiovascular disease. Robust diagnostic criteria are required for lipodystrophy, and subsequent prospective cohort studies and randomized controlled trials are then required to determine the etiology and prognosis of lipodystrophy, and to evaluate therapeutic interventions for this consequence of HAART. Therapies to improve insulin resistance have been tried but they are frequently ineffective, and are limited by potential toxicity in this population. Hence, current management options for HIV associated lipodystrophy are limited and are mostly based on avoidance of risk factors and switching of antiretroviral drugs.
As the '3 by 5 strategy' of providing HIV drugs to the developing world is implemented worldwide, the numbers of patients adhering to antiretroviral medicines is dramatically increasing. One must be aware that in reducing the burden of acute retroviral disease, the treatments proposed might lead to significant rates of metabolic complications and further exacerbation of the epidemic of diabetes and cardiovascular disease.
"This condition may have predisposed the patient to develop the disorder and could constitute a background that contributes to the final appearance of buffalo hump after raltegravir plus atazanavir treatment. Current data indicate that the etiology of HIV-associated Buffalo Hump remains elusive but is likely multifactorial and includes, metabolic disorders, genetic factors, receipt of ART and HIV infection itself . "
[Show abstract][Hide abstract] ABSTRACT: The availability of raltegravir plus atazanavir provides an alternative antiretroviral strategy that may be equally efficacious and less toxic than those currently recommended in HIV treatment guidelines. In fact, this new combination antiretroviral therapy attracts the attention of the scientific community because both drugs have a good safety profile coupled with potent antiviral activity, and their combined use would avert nucleoside- and ritonavir-related toxicities.
We describe the case of a 47-year-old, Caucasian woman treated for HIV-1 infection who developed Buffalo Hump during antiretroviral therapy, including raltegravir and unboosted atazanavir. Clinical evaluation and an ultrasonography scan of the cervical region showed a new progressive increase of lipohypertrophy and the results of DEXA confirmed these data. In our patient the worsening of the Buffalo Hump cannot be attributed to hypercortisolism; insulin-resistance, diabetes, dyslipidemia, hyperlactatemia and metabolic syndrome were not present. Moreover, she was not in therapy with antiretroviral drugs that are described as the cause of Buffalo Hump; on the other hand she developed this side effect three months after the switch of the antiretroviral therapy to raltegravir plus unboosted atazanavir.
Current data indicate that the etiology of HIV-associated Buffalo Hump remains elusive but is likely multifactorial; a possible contributing cause, but not the main cause, could be exposure to antiretroviral drugs. To the best of our knowledge, this is the first report on development of Buffalo Hump in the course of antiretroviral therapy, including the use of these drugs. On the basis of our data we can formulate the hypothesis of a pharmacological pathogenesis that underlies the development of this case of Buffalo Hump in the absence of other risk factors.
Journal of Medical Case Reports 02/2011; 5(1):70. DOI:10.1186/1752-1947-5-70
"Nucleoside reverse transcriptase inhibitors (NRTI) 56 such as stavudine are potent and efficacious components of this 57 therapy. Stavudine is no longer commonly used in well-resourced 58 settings due to high rates of toxicities such as lipoatrophy, neurop- 59 athy, pancreatitis, hepatic steatosis and lactic acidosis (Cossarizza 60 and Moyle, 2004; Martin et al., 1994; Cherry et al., 2005, 2006; 61 Nolan et al., 2003; SAHIV 2005; Waters and Nelson, 2007; Mallewa 62 et al., 2008; Wierzbicki et al., 2008). However, as stavudine is effec- 63 tive, available in generic fixed-dose combinations and associated 64 with lower rates of anemia than zidovudine, it remains widely 65 used in many resource-limited nations due to lack of practical, 66 affordable alternatives. "
[Show abstract][Hide abstract] ABSTRACT: HIV therapy with nucleoside analogue reverse transcriptase inhibitors (NRTI) such as stavudine remains in widespread use in resource-limited nations due to potent efficacy, convenience of formulation and lack of practical alternatives. However, it remains unclear whether adverse side effects with NRTI include reduced mitochondrial respiratory function, particularly in peripheral blood lymphocytes (PBLs). The aim of this study was to determine whether stavudine-based highly active antiretroviral therapy (HAART) is associated with impaired mitochondrial respiratory transport chain function in patient derived CD4+PBLs. CD4+PBLs were isolated from asymptomatic HIV-infected patients treated with stavudine-HAART for 3 months (n=10), HIV-infected patients not on treatment (n=9) and uninfected controls (n=18). The basal mitochondrial oxygen consumption of CD4+PBLs from stavudine-treated patients was reduced relative to that of untreated HIV-infected patients and controls (stavudine treated group, 4.22 (25% 2.16, 75% 8.84); control uninfected, 11.2 (25% 3.95, 75% 16.6); untreated 18.1 (25% 11.8, 75% 37.9)ng oxygen atoms/min/ml). Maximal oxygen consumption (stimulated with the proton ionophore FCCP) in cells from stavudine treated patients was also reduced relative to that of untreated patients and controls (stavudine treated, 24.4+/-10.5; control uninfected, 50.6+/-39.5; untreated, 68.8+/-41.1 ng oxygen atoms/min/ml). Citrate synthase activities, relative mitochondrial volume (by electron microscopy) and mtDNA copy numbers per cell were not different between groups. Therapy with stavudine results in impaired mitochondrial function in CD4+PBLs that does not appear to be due to reduced mitochondrial volume or DNA content and cannot be attributed to infection with HIV.
"Less is known about the mechanisms involved in the NRTIs effect on insulin sensitivity. It has been well documented that IR is related to abdominal obesity, hypertriglyceridaemia and is associated with type 2 DM There is much controversy as to whether it is changes in body composition that reflect underlying metabolic changes or vice versa. In a recently published study in which ART-naïve patients were randomised to receive either an NRTI-regimen or an NRTI-sparing regimen, glucose and insulin were assessed before and approximately three months after initiation of therapy. "
[Show abstract][Hide abstract] ABSTRACT: Africa is facing a rapidly growing chronic non-communicable disease burden whilst at the same time experiencing continual high rates of infectious disease. It is well known that some infections increase the risk of certain chronic diseases and the converse. With an increasing dual burden of disease in Sub Saharan Africa the associations between diseases and our understanding of them will become of increased public health importance.
In this review we explore the relationships reported between tuberculosis and diabetes mellitus, human immunodeficiency virus, its treatment and metabolic risk. We aimed to address the important issues surrounding these associations within a Sub Saharan African setting and to describe the impact of globalization upon them.
Diabetes has been associated with a 3-fold incident risk of tuberculosis and it is hypothesised that tuberculosis may also increase the risk of developing diabetes. During co-morbid presentation of tuberculosis and diabetes both tuberculosis and diabetes outcomes are reported to worsen. Antiretroviral therapy for HIV has been associated with an increased risk of developing metabolic syndrome and HIV has been linked with an increased risk of developing both diabetes and cardiovascular disease. Globalization is clearly related to an increased risk of diabetes and cardiovascular disease. It may be exerting other negative and positive impacts upon infectious and chronic non-communicable disease associations but at present reporting upon these is sparse.
The impact of these co-morbidities in Sub Saharan Africa is likely to be large. An increasing prevalence of diabetes may hinder efforts at tuberculosis control, increasing the number of susceptible individuals in populations where tuberculosis is endemic, and making successful treatment harder. Roll out of anti-retroviral treatment coverage within Sub Saharan Africa is an essential response to the HIV epidemic however it is likely to lead to a growing number of individuals suffering adverse metabolic consequences. One of the impacts of globalization is to create environments that increase both diabetes and cardiovascular risk but further work is needed to elucidate other potential impacts. Research is also needed to develop effective approaches to reducing the frequency and health impact of the co-morbidities described here.
Globalization and Health 09/2009; 5(1):9. DOI:10.1186/1744-8603-5-9 · 2.25 Impact Factor
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