Persistence of lipoatrophy after a four-year long interruption of antiretroviral therapy for HIV1 infection: case report
© Parruti and Toro; licensee BioMed Central Ltd. 2005
Received: 14 March 2005
Accepted: 03 October 2005
Published: 03 October 2005
HIV-infected patients on long-term highly active antiretroviral therapy often present peculiar patterns of fat redistribution, referred to as lipodystrophy. In spite of recent investigations, it is not known whether and to what extent the main features of lipodystrophy – that is lipoatrophy of peripheral fat at face, limbs and buttocks, as well as fat accumulation at breasts, abdomen and the dorso-cervical region – can be reversible once clinically manifest.
A 35 year old Caucasian HIV infected female developed severe diffuse lipodystrophy while on highly active antiretroviral therapy. A remarkable increase of breast size, fat accumulation at waist, and a fat pad on her lumbar spine were paralleled by progressive and disfiguring lipoatrophy of face, limbs and buttocks. The patient decided to interrupt her therapy after 20 months, with a stably suppressed viremia and a CD4 lymphocyte count >500/μL. She could carry on a safe treatment interruption for longer than 4 years. Most sites of fat accumulation switched to nearly normal appearance, whereas lipoatrophy was substantially unchanged at all affected sites.
our observation provides pictorial evidence that lipoatrophy may not be reversible even under ideal circumstances. Therefore, strategies to prevent lipoatrophy should be considered when defining therapeutic regimens for HIV infected patients, especially those at high risk.
HIV-infected patients on long-term highly active antiretroviral therapy (HAART) often present peculiar patterns of fat redistribution, involving both visceral and peripheral adipose tissue, referred to as lipodystrophy [1, 2]. This complex condition was recognized shortly after the introduction of HAART; to date, however, it has been poorly elucidated in terms of pathogenesis [3, 4]. Its main features are lipoatrophy of peripheral fat at face, limbs and buttocks, and/or fat accumulation at breasts, abdomen and the dorso-cervical region [3–5].
Complex methods for objective measurements of fat deposits on affected sites involve the use of Dual-energy X-ray absorptiometry, Magnetic Resonance Tomography or CT scans. These methods, however, are costly and not always accessible in routine clinical practice. Moreover, they still lack adequate standardization, so that the diagnosis of lipodystrophy more frequently relies on concordant patient's and physician's evaluation [3–5].
Cross sectional cohort studies indicate that lipodystrophy affects some 50% of patients continually treated with first-generation antiretroviral drugs for at least 18–24 months. Combined or severe abnormalities, however, develop only in 5 to 20% of affected patients [3–6], more frequently in older patients, females, patients with more advanced HIV disease and a longer exposure to antiretroviral drugs, especially stavudine and/or indinavir [6–8]. As to the evolution of body fat abnormalities, evidence has been gathered that once body changes become clinically evident, they generally tend to persist, improving only in a minority of cases .
Several strategies have been evaluated in clinical trials, with the aim of controlling such a stigmatizing side-effect. Switching to regimens including Nucleoside Reverse Transcriptase Inhibitors other than stavudine and/or a Non-Nucleoside Reverse Transcriptase Inhibitor instead of a Protease Inhibitor yielded objectively measured, significant increases in subcutaneous fat [10–12]; these, however, were not recorded as significant improvements by the affected patients, even after a long follow-up. At the same time, sites of fat accumulation were generally unmodified in parallel observations [10–12]. Some drugs are presently under evaluation for lipodystrophy, including metformine and rosiglitazone, with inconclusive results as yet [3, 5]. Finally, it is not clear whether and to what extent treatment interruptions may be helpful once lipodystrophy is clinically manifest.
Here we report on the evolution of HAART-induced severe combined lipodystrophy in one patient who carried out a very long lasting spell of therapy interruption.
Our observation provides pictorial evidence that severe combined lipodystrophy in our patient was only partially reversible, even under the ideal condition of a long lasting and safe interruption of HAART. Recent reports indicate that the loss of CD4 lymphocytes during treatment interruptions is frequently rapid in patients with a Nadir CD4 lymphocyte count <200/μL and a high rate of cell gain under treatment, irrespective of the level of CD4 lymphocyte count at the interruption of HAART [13, 14]. In spite of that, our patient could safely carry her interruption on for over 4 years, remaining asymptomatic throughout the period, with >200 CD4 T-lymphocytes/μL until late in 2003. She did eat a light and balanced diet; she reported taking L-carnitine (5 grams/daily) since June, 2000, until June, 2001, whereas she denied taking any other drug or supplement possibly interfering with lipid metabolism thereafter. Under these extremely favourable circumstances, sites of lumbar and waist fat accumulation reverted to nearly normal appearance, whereas breasts showed partial improvement (Fig. 1a). Such a clear-cut reversal of fat accumulation has not been reported in controlled trials investigating the efficacy of therapy switches [10–12], probably because of persistent interference with lipid metabolism caused by the new antiretroviral drugs [3–5].
Severe lipoatrophy at buttocks and legs, instead, was unchanged both on patient's and on our judgment (Fig. 1b, 1c and 1d). Although it is plausible that instrumental measurements at the affected sites might have detected partial improvements, our observation suggests that the loss of peripheral adipose tissue caused by HAART [3–5, 15] may not be fully reversible after treatment interruption, even in the long run.
Lipodystrophy represents a major drawback of antiretroviral therapy for HIV infection. Its clinical and psychological impact may ultimately jeopardize HAART efficacy in many cases [3, 5]. At the time of therapy interruption, our patient declared she would prefer dying rather than living with such disfiguring changes of her body shape. Recent studies systematically addressed the impact of severe lipodystrophy on patients' quality of life, documenting that body habit changes challenge compliance with therapy, as well as social relationships, performance of daily activities, sexuality and self-esteem, especially in young women .
As a growing body of clinical evidence suggests that newer HAART regimens may be less toxic on the adipose tissue, causing a clear-cut lower rate of body shape changes in the long run , prevention of lipodystrophy should become a key issue when tailoring individual regimens, particularly for patients at high risk of developing fat abnormalities on the basis of the available data.
List of abbreviations used
bis in die
highly active antiretroviral therapy
We are sincerely indebted with Mrs Loredana Puglielli, chief nurse in our Unit, for long lasting helpful assistance with this patient.
Written consent was obtained from the patient for publication of the present report.
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