Excisional lipectomy versus liposuction in HIV-associated lipodystrophy

Background Human immunodeficiency virus (HIV)-associated lipodystrophy is a known consequence of long-term highly active antiretroviral therapy (HAART). However, a significant number of patients on HAART therapy were left with the stigmata of complications, including fat redistribution. Few studies have described the successful removal of focal areas of lipohypertrophy with successful outcomes. This manuscript reviews the outcomes of excisional lipectomy versus liposuction for HIV-associated cervicodorsal lipodystrophy.Methods We performed a 15-year retrospective review of HIV-positive patients with lipodystrophy. Patients were identified by query of secure operative logs. Data collected included demographics, medications, comorbidities, duration of HIV, surgical intervention type, pertinent laboratory values, and the amount of tissue removed.Results Nine male patients with HIV-associated lipodystrophy underwent a total of 17 procedures. Of the patients who underwent liposuction initially (n=5), 60% (n=3) experienced a recurrence. There were a total of three cases of primary liposuction followed by excisional lipectomy. One hundred percent of these cases were noted to have a recurrence postoperatively, and there was one case of seroma formation. Of the subjects who underwent excisional lipectomy (n=4), there were no documented recurrences; however, one patient’s postoperative course was complicated by seroma formation.Conclusions HIV-associated lipodystrophy is a disfiguring complication of HAART therapy with significant morbidity. Given the limitations of liposuction alone as the primary intervention, excisional lipectomy is recommended as the primary treatment. Liposuction may be used for better contouring and for subsequent procedures. While there is a slightly higher risk for complications, adjunctive techniques such as quilting sutures and placement of drains may be used in conjunction with excisional lipectomy.

Didanosine-Associated Retinal Toxicity in a Patient With a Mutation in the CRB1 Gene

Purpose: This article describes a case of didanosine (DDI)-associated retinal toxicity in a patient with a heterozygous pathogenic variant in the CRB1 gene. Methods: Case report. Results: A middle-aged patient with HIV controlled on HAART therapy, and a remote 10-year year history of treatment with DDI and tenofivir, presented with external ophthalmoplegia and well-circumscribed, midperipheral patterns of bilateral pigmentary retinopathy and chorioretinal atrophy in both eyes. Genetic testing revealed a heterozygous pathogenic variant in the CRB1 gene that encodes a protein (Crumbs homolog 1) involved in regulation of cell polarity and junctions and is localized adjacent to mitochondria in the ellipsoid and myoid area. Conclusions: This case highlights a potential role for genetic susceptibility to retinal toxicity in DDI-associated retinal toxicity. Large, prospective pharmacogenomics studies may be informative to further elucidate the role of genetic risk factors in drug-induced retinal toxicity.

A case series of efavirenz induced gynaecomastia

The prognosis of HIV infection has significantly changed following the introduction of highly active anti-retroviral therapy by reducing AIDS related morbidity and mortality. At the same time, HAART is documented for its side effects. Gynaecomastia is a less documented side effect of a commonly used ART drug efavirenz. There are only few case reports of HAART-induced gynaecomastia in resource limited settings. Initially gynaecomastia related to HAART in HIV patients was thought due to lipodystrophy and was termed as pseudogynaecomastia. Later, few case reports of efavirenz related gynaecomastia were published after ruling out other causes of gynaecomastia. All other causes of gynaecomastia were ruled out in our patients too. The incidence of gynaecomastia is increasing in men with HIV on HAART therapy, proper identification and management will promote better drug adherence. The present study presented a series of two cases that developed ultrasound confirmed gynaecomastia following efavirenz containing HAART.

Molecular Basis for Reduced Cleavage Activity and Drug Resistance in D30N HIV-1 protease

Nelfinavir is one of the FDA approved HIV-1 protease inhibitors and is a part of HAART therapy for the treatment of HIV-AIDS. Nelfinavir was the first HIV-1 protease inhibitor to be approved as a Paediatric formulation. The application of HAART had resulted into significant improvement in the life of AIDS patients. However, emergence of drug resistance in HIV-1 protease limited the use of many of these drugs including nelfinavir. A unique mutation observed frequently in patients treated with nelfinavir is D30N as it is selected exclusively by nelfinavir. It imparts very high resistance to nelfinavir but unlike other primary mutations does not give cross resistance to the majority of other drugs. D30N mutation also significantly reduces cleavage activity of HIV-1 protease and affects the viral fitness. Here, we have determined structures of D30N HIV-1 protease in unliganded form and in complex with the drug nelfinavir. These structures provide rationale for rduced cleavage activity and molecular basis of resistance induced by D30N mutation. The loss of coulombic interaction part of a crucial hydrogen bond between the drug and the enzyme, is a likely explanation for reduced affinity and drug resistance towards nelfinavir. The decreased catalytic activity of D30N HIV protease, due to altered interaction with substrates and reduced stability of folding core may be the reasons for reduced replicative capacity of the HIV harboring D30N HIV-1 protease.

Treatment of HIV-associated pulmonary arterial hypertension: single-center experience

Introduction Currently there is no evidence-based strategy for PAH drug application adjusted for patients with HIV-associated PAH. Data regarding the use of sildenafil and endothelin receptors antagonists (ERA) are limited case series. Purpose To present the long-term data on treatment with sildenafil, macitentan and ambrisentan in pts with HIV-PAH. Material and methods In prospective study were consecutively enrolled 18 treatment-naïve pts with HIV-PAH (7 males, 34.5 yrs; 29; 53 yrs), mean follow-up was 1.64yrs; 0,16–59–9.28 yrs. 4 pts were in IV FC, 5-III FC and 9 in II FC PAH (WHO). RHC, ECHO, 6MWT, ergospirometry and NTproBNP level were evaluated at a baseline. Intravenous drug abuse reported in 72% pts, all of them were co-infected with hepatitis. Nine pts (50%) treated with HAART therapy at a baseline. Five pts did not have PAH-specific therapy, 11 pts received sildenafil, 1 IV FC PAH pt with HAART – sildenafil+macitentan and 1 III FC PAH pt with HAART-sildenafil+ambrisentan. Follow-up data (FC, 6MWT, ECHO, ergospirometry, NT-proBNP) were available for 8 PAH-treated pts. Results Pts on PAH therapy had achieved improvement in 6 MWT with mean distance increase 69.3±52 m (p=0.01); NTproBNP level decrease (p=0.018) and FC PAH improvement in 7 pts. In pts with PAH therapy the size of right atrium decreased (56.4±7.8 vs 47.8±6.7 mm, p=0.027). The combinations of sildenafil and macitentan and sildenafil with ambrisentan were well tolerated and resulted 6MWT increase, low NTproBNP and FC improvement. Nevertheless there was no significant changes in peak VO2 consumption. Two pts with sildenafil therapy lost for follow up. Three pts with sildenafil but without HAART therapy dead: in one case due to pneumonia, other 2 cases due to pulmonary embolism. Four pts without HAART and PAH therapy dead. In our population strong association between survival and HAART therapy presence was revealed (p=0.01). Conclusion No adverse reactions of PAH-specific therapy were reported in pts on HAART. PAH therapy had a positive influence on FC, exercise capacity, heart remodeling and NT-proBNP level. There were no deaths in pts who receive HAART and PAH therapy. Nevertheless in our population strong association between survival and HAART therapy presence was revealed. Funding Acknowledgement Type of funding source: None

Efavirenz induced gynecomastia, hidden reality: a case series

The prognosis of HIV infection has considerably improved following the introduction of highly active anti-retroviral therapy by reducing AIDS related morbidity and mortality. At the same time, ART drugs are well known for their side effects. Gynaecomastia is a lesser known side effect of a commonly used anti-retroviral drug efavirenz. There are very few reports of HAART-induced gynaecomastia in resource-limited settings. The current study presents a series of three cases that developed ultrasound confirmed gynaecomastia following efavirenz containing HAART. Initial reports of gynaecomastia related to HAART were in HIV patients with lipodystrophy, they were termed as pseudogynaecomastia. Gradually, few reports of efavirenz related gynaecomastia were published wherein other causes of gynaecomastia were ruled out. Several hypothesis have been suggested for the pathophysiology of development of gynaecomastia related to efavirenz consumption. All other causes were ruled out in our patients too. The incidence of gynaecomastia is increasing in men with HIV on HAART therapy, proper identification and management will promote better drug adherence.

HAART THERAPY IN GHANA: COMPARATIVE ASSESSMENT OF THE EFFECTIVENESS OF DIFFERENT HAART COMBINATIONS AT KOMFO ANOKYE TEACHING HOSPITAL

Objective: Although all marketed antiretrovirals (ARVs) have proven efficacy, genetic differences can result in varied effectiveness. This study was conducted to determine the effectiveness of different Highly Active Antiretroviral Therapy (HAART) combinations among patients attending HIV clinic at a Major Teaching Hospital in Ghana. Methods: The study was a retrospective study involving 500 patients at an HIV clinic in the Ashanti Region of Ghana. Results: Twelve major antiretroviral combinations for HAART were prescribed at the study center. The most prescribed drug combinations were AZT+3TC+EFV and AZT+3TC+NVP. The study identified that HAART, irrespective of the kind of drug combination used, was effective at increasing CD4 count within the first 6 mo of therapy initiation in the study population. However, the magnitude of the increases differed from combination to combination. All HAART combinations with zidovudine as one of the drugs resulted in higher CD4 counts compared with combinations containing stavudine. HAART with nevirapine also resulted in a higher CD4 count than those with efavirenz. However, efavirenz-based combinations appeared to be more effective in critically ill patients and patients with mean CD4+T helper cells count below 100 cell/mm3. More importantly, efavirenz was common among all HAART combinations that resulted in treatment failure. Conclusion: There was significant variation in response to different HAART combination among Ghanaian HIV patients. However, there was no statistically significant difference in mean CD4 count between the two most predominately used HAART i. e AZT+3TC+EFV and AZT+3TC+NVP.