Antiretroviral therapy induced cervicodorsal lipohypertrophy needing surgical excision: case series

• Vivek R.U.
• Sunil K.M.
• Ruqaiya A.

Abstract

HIV is still a major global public health issue. By the end of 2022, approximately 39.0 million people were detected with HIV. In which, 29.8 million were receiving antiretroviral therapy (ART) worldwide and of those 93% had suppressed viral loads. However, ART can be a boon and a bane; it preserves our immune functions and suppresses viral replication, but long-term use of ART is found to cause many metabolic complications like lipodystrophy syndrome. Lipodystrophy can manifest either as lipohypertrophy, lipoatrophy or mixed. Incidence of HIV-associated lipodystrophy syndrome ranges from 10 to 80 per cent, but buffalo hump or cervicodorsal lipohypertrophy has been reported in only 1–2 per cent of cases. Here we will discuss two rare cases of ART induced lipohypertrophy which required surgical intervention.

Keywords:HIV; antiretroviral therapy; lipohypertrophy

A male patient in his late 40s presented with swelling over the nape of the neck for 3 years, which was gradually progressive. He was a known case of HIV disease on AntiRetroviral Therapy (ART) for 15 years. Since last 3 years patient is on zidovuine (ZDV), lamivudine (3TC) and dolutegravir (DTG) regimen from Governmental ART centre. Initial size of the swelling was around 5×5 cm and progressed to present size of around 20×15 cm over 3 years. It was associated with dull aching pain. The patient could not lie supine due to the enormous swelling and had to sleep in a lateral position. On examination the swelling was in nape of neck, diffuse in subcutaneous plane and around 20×15 cm size. Patient also had features of lipodystrophy in face and abdomen. Routine blood investigations were normal, CD4 counts were 386 cells/mm³. RNA viral load was <50 copies/ml. He underwent MRI of neck, it showed non capsulated cervico-dorsal subcutaneous fat proliferation, underlying muscles appeared normal with no significant cervical lymphadenopathy. The decision to operate was taken as the patient was symptomatic, and lipohypertrophy was causing a significant disturbance in his sleep (fig. 1, 2).

The patient underwent excision of the swelling under general anaesthesia (fig. 3). Excised specimen weighed 750 grams (fig. 4). Post-operative period was uneventful. Histopathology report showed features suggestive of lipoma. Modification in ART regime was done, zidovudine was switched to tenofovir. On follow-up wound was healthy, patient’s symptoms significantly improved.

Case 2

A 16-year-old girl presented with diffuse swelling over her nape of neck, involving the upper back for 10 years. She had difficulty while lying in supine position because of the size of swelling, however, there were no restrictions in neck movements. No abnormal deposition of fat anywhere else in the body. She was detected since birth with the retroviral disease and is compliant on her anti-retroviral regimen (zidovudine 300 mg twice daily; lamivudine 150 mg twice daily; dolutegravir 50 mg once daily). She has a positive family history of retroviral disease related to her parents.

Physical examination revealed a diffuse swelling over nape of neck approximately 30×20 cm, non-tender, soft in consistency extending till lower border of scapula (fig. 5). Absolute CD4 count, HIV-1 RNA viral load and antibodies to HIV (done by chemiluminescence method) were 993.49 cells/μl, <40 copies/ml and reactive, respectively.

Ultrasound of the neck revealed a large ill-defined iso-hyperechoic 30×20 cm lesion with sub-cutaneous fat like echogenicity, at posterior aspect of neck, upper back and interscapular region. Features were suggestive of cervico-dorsal fat pad/lipomatosis.

The patient underwent surgical excision of this swelling due to cosmetic concerns and inability to sleep (fig. 6, 7). Excised specimen weighed 800 grams (fig. 8). Postoperative period was uneventful. Based on review done by Infectious Disease Department before discharge, Zidovudine was switched to tenofovir. On follow-up, wound was healthy, patient’s symptoms improved.

 Discussion

ART induced lipodystrophy can present either with lipohypertrophy (fat accumulation) or lipoatrophy (fat loss) or these two distinct manifestations may coexist as well. Lipohypertrophy usually exhibited symptoms of buffalo hump (dorsocervical fat pad) or fat accumulation in abdominal wall, breasts, thighs, gluteal region and anterior neck. On the other hand, lipoatrophy is characterized by fast loss in subcutaneous tissue in arms, legs, face and buttocks [4].

The causes of lipodystrophy are multifactorial, and includes patient and treatment factors. Older age (older than 40 years of age) [4–7], female sex [8, 9], elevated serum triglyceride level [10], low nadir CD4 cell count [11] and an advanced stage of HIV infection [12] have all been identified as risk factors for lipodystrophy.

Nucleoside reverse transcriptase inhibitors (NRTI(s) are most often associated with lipoatrophy and protease inhibitor (PI(s) based regimen are associated with lipohypertrophy. NRTIs are strongly associated with the loss of subctaneous fat and hyperlactatemia due to mitochondrial damage, while PIs are more closely associated with lipoaccumulation and effects on lipid metabolism and insulin resistance due to dysfunction in adipocyte differentiation. The effects of NRTIs appear to be augmented or accelerated when combined with PI [13, 14], and the manifestations of lipodystrophy are different than in patients receiving NRTIs alone [11, 13].

Treatment options for patients with lipohypertrophy, holistically are as follow: since risk factors for lipohypertrophy are more of host factors like high caloric diet, female gender, higher body fat % at baseline and therefore, dietary counselling and lifestyle modifications (combination of strength and cardiovascular training) helps to prevent the risk of fat accumulation again [1, 4].

Patients on protease inhibitors, can be prescribed with lose-dose atorvastatin (pravastatin) orfluvastatin with dose adjustments to avoid statin toxicity [1].Consultation of psychology department should be sought, in view of associated poor body image and anxiety [4].

Lipohypertrophy is surgically treated by liposuction or lipectomy. In a retrospective study done in 2021 [15], on 9 HIV-positive patients with lipodystrophy, 5 of them had undergone liposuction, out of which 3 (60%) had experienced recurrence and 1 had seroma formation. However, rest 4 patients who underwent lipectomy had 0 recurrences and 1 seroma complication in follow up.

Warren et al. [16] study showed 7 patients undergoing excision lipectomy with no recurrence on 26 month follow up.

Hultman et al. [17] showed that despite the potential for recurrence, surgical management of HIV-associated lipodystrophy was efficacious with minimal morbidity. Ultrasonic assisted liposuction and suction assisted lipectomy were particularly beneficial in reducing the cervicodorsal fat pad.

Barton et al. [15] compared excision lipectomy and liposuction and concluded excisional lipectomy as the primary treatment that considering the limitations of liposuction alone as the primary intervention.

Both patient in our study underwent excision lipectomy due to diffuse and enormous size of the swelling.

Lipohypertrophy can cause decreased self-esteem, quality of life, and social stigma due to visible abnormality. It can also have a significant effect on drug adherence.

There is no consensus on the most effective therapy for lipodystrophy. Switching of drug regimens alone may not alter the course of lipodystrophy. Hence, managing large cervicodorsal lipohypertrophy is mainly surgical, along with the change of ART regimen.

Conclusion

• HIV-associated lipodystrophy progressively worsens when protease inhibitors and thymidine analog NRTIs therapy continues.

• Altering body image and self-esteem may lead to poor compliance with antiretroviral therapy and treatment failure.

• Early identification and management of HIV-associated metabolic complications can halt the progression of these conditions and, in some cases, may help reverse lipodystrophy.

• Surgical management remains the mainstay with excision lipectomy and ultrasonic liposuction as preferred modalities.

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