Nucleoside Analogue Reverse Transcriptase Research Articles

Nucleoside Analog Reverse-Transcriptase Inhibitors in Membrane Environment: Molecular Dynamics Simulations.

The behavior of four drugs from the family of nucleoside analog reverse-transcriptase inhibitors (zalcitabine, stavudine, didanosine, and apricitabine) in a membrane environment was traced using molecular dynamics simulations. The simulation models included bilayers and monolayers composed of POPC and POPG phospholipids. It was demonstrated that the drugs have a higher affinity towards POPG membranes than POPC membranes due to attractive long-range electrostatic interactions. The results obtained for monolayers were consistent with those obtained for bilayers. The drugs accumulated in the phospholipid polar headgroup region. Two adsorption modes were distinguished. They differed in the degree of penetration of the hydrophilic headgroup region. Hydrogen bonds between drug molecules and phospholipid heads were responsible for adsorption. It was shown that apricitabine penetrated the hydrophilic part of the POPC and POPG membranes more effectively than the other drugs. Van der Waals interactions between S atoms and lipids were responsible for this.

Prevalence of HLA-B*57:01 allele in HIV-positive and HIV-negative population of eastern India: An epidemiological study

IntroductionThe nucleoside analogue reverse-transcriptase inhibitor Abacavir has potent antiviral activity against HIV; however, 5–8% patients develop hypersensitivity reactions within six weeks of treatment. The presence of the HLA-B*57:01 allele is strongly associated with the risk of Abacavir-associated hypersensitivity reaction (ABC-HSR). Prevalence of HLA-B*57:01 allele varies in different populations. This observational study was performed to determine the prevalence of HLA-B*57:01 allele in the population of Eastern India which included both HIV-positive and HIV-negative subjects. MethodsWe screened 406 subjects attending the ART (antiretroviral treatment) centre and linked ICTC (Integrated counselling and testing centre), however 6 samples did not have adequate DNA. HLA-B*57:01 typing was done using direct sequence specific primer PCR (SSP-PCR). All PCR positive samples were sequenced using Sanger's method. ResultsThe prevalence of HLA-B*57:01 genotype in our cohort was 12.25% (49/400). Prevalence among men was 13.3% (33/248) and female was 10.5% (16/152). The prevalence was similar in HIV-positive subjects (13.5%) and in HIV-negative subjects (11%). ConclusionsPrevalence of HLA-B*57:01 in our eastern Indian population was high. Therefore, screening for HLA-B*57:01 before ABC administration would be useful to prevent ABC-HSR.

Prevalence of Drug Resistance and Genetic Transmission Networks Among Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Patients with Antiretroviral Therapy Failure in Guangxi, China.

Prevalence of drug resistance (DR) challenges the epidemic control of human immunodeficiency virus (HIV)-1. However, little is known about DR among patients with antiretroviral therapy (ART) failure in Guangxi province, China. This cross-sectional study was aimed to investigate the prevalence of DR and the characteristics of DR sequences in the genetic transmission network among HIV-1 patients with ART failure in Guangxi. We enrolled 358 eligible patients between 2012 and 2018. Blood samples were subjected to reverse transcription polymerase chain reaction, followed by sequencing of the HIV-1 polymerase (pol) gene. An online subtyping tool and neighbor-joining phylogenetic tree were used to determine the genotype. HIV-TRACE tool was used to constructed transmission network with a pairwise genetic distance of 0.013. DR was analyzed using the Stanford University HIV Drug Resistance Database. We obtained 293 pol-sequences from participants; CRF01_AE (75.4%), CRF 08_BC (15.7%), and CRF07_BC (8.5%) were the main subtypes, and an A1 subtype was detected in Guangxi for the first time. The overall prevalence of DR was 32.4% (95/293). Among those with identified DR, 25.6% were against non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs), 17.7% were against nucleoside analog reverse-transcriptase inhibitors (NRTIs), and 14.3% were against both NRTIs and NNRTIs. The common drug-resistant mutations were M184V (10.2%), K103N (10.6%) and V179D (6.1%). The patients located in the southern Guangxi [adjust odds ratio (AOR) = 10.87], or whose blood plasma were taken in 2017-2018 (AOR = 3.98) had an increased risk of DR. Of the CRF01_AE, CRF07_BC, and CRF08_BC sequences, 18.6%, 8.0%, and 13.0% fell into clusters, respectively. Nine (9.7%) sequences from patients with DR fell into three clusters. The largest cluster containing 11 individuals was the CRF01_AE subtype, 27.3% of whom were DR patients. Although the prevalence of DR among ART failure patients in Guangxi was at a low level, the continuous surveillance of DR in ART patients is necessary.

Genetic and cytometric analyses of subcutaneous adipose tissue in patients with hemophilia and HIV-associated lipodystrophy

BackgroundThe authors recently performed plastic surgeries for a small number of patients with hemophilia, HIV infection, and morphologic evidence of lipodystrophy. Because the pathophysiological mechanism of HIV-associated lipodystrophy remains to be elucidated, we analyzed subcutaneous adipose tissues from the patients.MethodsAll six patients had previously been treated with older nucleoside analogue reverse-transcriptase inhibitors (NRTIs; stavudine, didanosine or zidovudine). Abdominal and inguinal subcutaneous fat samples were obtained from the HIV+ patients with hemophilia and HIV− healthy volunteers (n = 6 per group), and analyzed via DNA microarray, real-time PCR, flow cytometry and immunohistochemistry.ResultsThe time from initial NRTI treatment to collecting samples were 21.7 years in average. Cytometric analysis revealed infiltration of inflammatory M1 macrophages into HIV-infected adipose tissue and depletion of adipose-derived stem cells, possibly due to exhaustion following sustained adipocyte death. Genetic analysis revealed that adipose tissue from HIV+ group had increased immune activation, mitochondrial toxicity, chronic inflammation, progressive fibrosis and adipocyte dysfunction (e.g. insulin resistance, inhibited adipocyte differentiation and accelerated apoptosis). Of note, both triglyceride synthesis and lipolysis were inhibited in adipose tissue from patients with HIV.ConclusionsOur findings provide important insights into the pathogenesis of HIV-associated lipodystrophy, suggesting that fat redistribution may critically depend on adipocytes’ sensitivity to drug-induced mitochondrial toxicity, which may lead either to atrophy or metabolic complications.

An Overview of Human Immunodeficiency Virus-1 Antiretroviral Drugs: General Principles and Current Status.

Treatment with highly active antiretroviral therapy (HAART) can prolong a patient's life-span by disrupting pivotal steps in the replication cycle of the human immunodeficiency virus-1 (HIV-1). However, drug resistance is emerging as a major problem worldwide due to the prolonged period of treatment undergone by HIV-1 patients. Since the approval of zidovudine in 1987, over thirty antiretroviral drugs have been categorized into the following six distinct classes based on their biological function and resistance profiles: (1) nucleoside analog reverse-transcriptase inhibitors; (2) non–nucleoside reverse transcriptase inhibitors; (3) integrase strand transferase inhibitors; (4) protease inhibitors; (5) fusion inhibitors; and (6) co-receptor antagonists. Additionally, several antiretroviral drugs have been developed recently, such as a long active drug, humanized antibody and pro-drug metabolized into an active form in the patient's body. Although plenty of antiretroviral drugs are beneficially used to treat patients with HIV-1, the ongoing efforts to develop antiretroviral drugs have overcome the drug resistances, adverse effects, and limited adherence of drugs observed in previous drugs to some extent. Furthermore, studies focused on agents targeting latent HIV-1 reservoirs should be strengthened, as that may lead to eradication of HIV-1.

CGAS/STING Pathway Activation Contributes to Delayed Neurodegeneration in Neonatal Hypoxia-Ischemia Rat Model: Possible Involvement of LINE-1

cGAS is a sensor of cytosolic DNA and responds equally to exogenous and endogenous DNA. After recognition of cytosolic dsDNA or ssDNA, cGAS synthesizes the second messenger 2'3'-cGAMP, which then binds to and activates stimulator of interferon genes (STING). STING plays an essential role in responding to pathogenic DNA and self-DNA in the context of autoimmunity. In pathologic conditions, such as stroke or hypoxia-ischemia (HI), DNA can gain access into the cytoplasm of the cell and leak from the dying cells into the extracellular environment, which potentially activates cGAS/STING. Recent in vivo studies of myocardial ischemia, traumatic brain injury, and liver damage models suggest that activation of cGAS/STING is not only a side-effect of the injury, but it can also actively contribute to cell death and apoptosis. We found, for the first time, that cGAS/STING pathway becomes activated between 24 and 48h after HI in a 10-day-old rat model. Silencing STING with siRNA resulted in decreased infarction area, reduced cortical neurodegeneration, and improved neurobehavior at 48h, suggesting that STING can contribute to injury progression after HI. STING colocalized with lysosomal marker LAMP-1 and blocking STING reduced the expression of cathepsin B and decreased the expression of Bax and caspase 3 cleavage. We observed similar protective effects after intranasal treatment with cGAS inhibitor RU.521, which were reversed by administration of STING agonist 2'3'-cGAMP. Additionally, we showed that long interspersed element 1 (LINE-1) retrotransposon, a potential upstream activator of cGAS/STING pathway was induced at 48h after HI, which was evidenced by increased expression of ORF1p and ORF2p proteins and increased LINE-1 DNA content in the cytosol. Blocking LINE-1 with the nucleoside analog reverse-transcriptase inhibitor (NRTI) stavudine reduced infarction area, neuronal degeneration in the cerebral cortex, and reduced the expression of Bax and cleaved caspase 3. Thus, our results identify the cGAS/STING pathway as a potential therapeutic target to inhibit delayed neuronal death after HI.

Characterization of HIV-1 genetic diversity and antiretroviral resistance in the state of Maranhão, Northeast Brazil.

The HIV-1 epidemic in Brazil has been growing in northeast and north regions, particularly an increase in AIDS cases among the younger male population has been observed. This study aims to characterize the HIV-1 genetic diversity and to evaluate its antiretroviral resistance profile among individuals presenting virological failure in the state of Maranhão—Brazil. HIV-1 pol gene sequences from 633 patients on antiretroviral therapy were obtained from the Department of Surveillance, Prevention and Control of Sexually Transmitted Infections, HIV/AIDS and Viral Hepatitis of the Brazilian Ministry of Health. Phylogenetic and recombination analyses were performed to characterize viral genetic diversity. The presence of antiretroviral resistance mutations was assessed using the HIV Drug Resistance Database online platform of Stanford University. A predominance of subtype B (84.5%) was observed, followed by recombinant BF (9.5%), where more than half of the sequences were dispersed in 3 clusters. Antiretroviral resistance was detected in 74.1% of the sequences, and it was significantly higher for nucleoside analogue reverse-transcriptase inhibitors (NRTIs) than for non-nucleoside analogue reverse-transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). Inference of putative transmissions clusters identified 11 clusters with 22 query sequences (22/633, 3.5%). Thus, we conclude that continuous monitoring of the molecular epidemiology of HIV-1 is essential for prevention strategies, epidemic control, and treatment adequacy.

Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine

Chronic hepatitis B virus (HBV) infection is a major public health problem that affects millions of people worldwide. Nucleoside analogue reverse transcriptase (RT) inhibitors, such as entecavir (ETV) and lamivudine (3TC), serve as crucial anti-HBV drugs. However, structural studies of HBV RT have been hampered due to its unexpectedly poor solubility. Here, we show that human immunodeficiency virus type-1 (HIV-1) with HBV-associated amino acid substitutions Y115F/F116Y/Q151M in its RT (HIVY115F/F116Y/Q151M) is highly susceptible to ETV and 3TC. Additionally, we experimentally simulated previously reported ETV/3TC resistance for HBV using HIVY115F/F116Y/Q151M with F160M/M184V (L180M/M204V in HBV RT) substituted. We determined crystal structures for HIV-1 RTY115F/F116Y/Q151M:DNA complexed with 3TC-triphosphate (3TC-TP)/ETV-triphosphate (ETV-TP)/dCTP/dGTP. These structures revealed an atypically tight binding conformation of 3TC-TP, where the Met184 side-chain is pushed away by the oxathiolane of 3TC-TP and exocyclic methylene of ETV-TP. Structural analysis of RTY115F/F116Y/Q151M/F160M/M184V:DNA:3TC-TP also demonstrated that the loosely bound 3TC-TP is misaligned at the active site to prevent a steric clash with the side chain γ-methyl of Val184. These findings shed light on the common structural mechanism of HBV and HIV-1 resistance to 3TC and ETV and should aid in the design of new agents to overcome drug resistance to 3TC and ETV.

Active-site deformation in the structure of HIV-1 RT with HBV-associated septuple amino acid substitutions rationalizes the differential susceptibility of HIV-1 and HBV against 4ʹ-modified nucleoside RT inhibitors

Nucleoside analogue reverse transcriptase (RT) inhibitors (NRTIs) are major antiviral agents against hepatitis B virus (HBV) and human immunodeficiency virus type-1 (HIV-1). However, the notorious insoluble property of HBV RT has prevented atomic-resolution structural studies and rational anti-HBV drug design. Here, we created HIV-1 RT mutants containing HBV-mimicking sextuple or septuple amino acid substitutions at the nucleoside-binding site (N-site) and verified that these mutants retained the RT activity. The most active RT mutant, HIV-1 RT7MC, carrying Q151M/G112S/D113A/Y115F/F116Y/F160L/I159L was successfully crystallized, and its three-dimensional structure was determined in complex with DNA:dGTP/entecavir-triphosphate (ETV-TP), a potent anti-HBV guanosine analogue RT inhibitor, at a resolution of 2.43 Å and 2.60 Å, respectively. The structures reveal significant positional rearrangements of the amino acid side-chains at the N-site, elucidating the mechanism underlying the differential susceptibility of HIV-1 and HBV against recently reported 4ʹ-modified NRTIs.

Chemical structure and correlation analysis of HIV-1 NNRT and NRT inhibitors and database-curated, published inhibition constants with chemical structure in diverse datasets

Human immunodeficiency virus (HIV-1) reverse transcriptase is a major target for designing anti-HIV drugs. Developed inhibitors are divided into non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs) and nucleoside analog reverse-transcriptase inhibitors (NRTIs) depending on their mechanism. Given that many inhibitors have been studied and for many of them binding affinity constants have been calculated, it is beneficial to analyze the chemical landscape of these families of inhibitors and correlate these inhibition constants with molecular structure descriptors. For this, the HIV-1 RT data was retrieved from the ChEMBL database, carefully curated, and original literature verified, grouped into NRTIs and NNRTIs, analyzed using a hierarchical scaffold classification method and modelled with best multi-linear regression approach. Analysis of the HIV-1 NNRTIs subset results in ten different common structural parent types of oxazepanone, piperazinone, pyrazine, oxazinanone, diazinanone, pyridine, pyrrole, diazepanone, thiazole, and triazine. The same analysis for HIV-1 NRTIs groups structures into four different parent types of uracil, pyrimide, pyrimidione, and imidazole. Each scaffold tree corresponding to the parent types has been carefully analyzed and examined, and changes in chemical structure favorable to potency and stability are highlighted. For both subsets, descriptive and predictive QSAR models are derived, discussed and externally validated, revealing general trends in relationships between molecular structure and binding affinity constants in structurally diverse datasets. Data and QSAR models are available at the QsarDB repository (http://dx.doi.org/10.15152/QDB.202).

Zidovudina/Lamivudina vs Abacavir/Lamivudina vs Tenofovir/Emtricitabina en combinaciones de dosis fija como tratamiento inicial en pacientes con VIH: revisión sistemática y metanálisis en red

Initial treatment of the HIV is based on the use of three drugs, two of which are nucleoside analog reverse-transcriptase inhibitors. There are three combinations of these drugs which have been approved by different guidelines, each with divergent results in terms of efficacy and safety. To compare the efficacy and safety of these three combinations. Systematic review and network meta-analysis of randomized clinical trials comparing fixed doses of Tenofovir Disoproxil Fumarate / Emtricitabine (TDF/FTC), Abacavir / Lamivudine (ABC/3TC) and Zidovudine / Lamivudine (ZDV/3TC). Seven clinical trials met the eligibility criteria. The results suggested higher efficacy with TDF/FTC vs. ABC/3TC at 96 weeks and vs. ZDV/3TC at 48 weeks. However, there is clinical and statistical heterogeneity. Subgroup analysis were performed by third drug and by level of viral load prior to treatment, and found no differences in virological control. Network meta-analysis could only be carried out with TDF/FTC vs. ZDV/3TC, and the proportion of patients with virological response, with no differences at 48 weeks nor at 96 weeks. Direct comparisons showed an increased risk of bone marrow suppression of ZDV/3TC vs. TDF/FTC and of ABC/3TC hypersensitivity reactions vs. ZDV/3TC. The results did not show differences in effectiveness among the interventions. However, due to the heterogeneity of the third drug and the follow-up time between the included studies, this result is not definitive. The results raise the need for further studies to help improve treatment recommendations in patients infected with HIV.

High prevalence and incidence of HIV-1 in a counseling and testing center in the city of Itajaí, Brazil

Itajaí is a port city in southern Brazil with one of the highest incidence and mortality rates from AIDS in the country. The prevalence and incidence of HIV infection were investigated in 1085 of 3196 new HIV-1 infection cases evaluated in the counseling and testing center of Itajaí from January 2002 to August 2008. Recent infections were assessed using the BED™, and pol region sequencing was performed in 76 samples. The prevalence ranged from 3.08% to 6.17% among women and from 10.26% to 17.36% among men. A total of 17% of infections were classified as recent, with annual incidence varying from 1.6% to 4.8 per 100 patient/year among women and from 2.05% to 8.5 per 100 patient/year among men. Pol sequences were obtained from 38 randomly recent infections selected individuals: 71% were infected by subtype C, 24% B, 2% D, and 2% F1. Among 38 subjects with established infection, 76% were subtype C, and 24% B. Transmitted drug resistance was detected in 18.4% of recent infection subjects (7.8% to nucleoside analog reverse-transcriptase inhibitors, 5.2% to non-nucleoside reverse-transcriptase inhibitors, and 5.2% protease inhibitors) and 5.2% of subjects with established infection had nucleoside analog reverse-transcriptase inhibitors resistance.The high prevalence and incidence of HIV infection in this region is unprecedented in studies involving cases evaluated in the counseling and testing centers in Brazil.

Discovering novel direct acting antiviral agents for HBV using in silico screening

The treatments for chronic hepatitis B (CHB) are interferon and nucleoside analogues reverse transcriptase (RT) inhibitors. Because both treatments are less than ideal, we conducted to identify novel anti-viral agents for HBV-reverse transcriptase (HBV-RT). We determined the ligand-binding site of the HBV-RT by conducting a homological search of the amino acid sequence and then we also determined not only structural arrangement of the target protein but the target protein-binding site of the ligand using known protein–ligand complexes in registered in the protein data bank (PDB). Finally we simulated binding between the ligand candidates and the HBV-RT and evaluated the degree of binding (in silico screening). PXB cells derived from human-mouse chimeric mouse liver, infected with HBV were administrated with the candidates, and HBVDNA in the culture medium was monitored by realtime qPCR. Among compounds from the AKosSamples database, twelve candidates that can inhibit RT were also identified, two of which seem to have the potential to control HBV replication in vitro.

Lopinavir/ritonavir en nuevas estrategias de tratamiento antirretroviral de inicio

According to evidence from randomized controlled trials and epidemiological data, the antiretroviral treatment (ART) of choice has consisted of the combination of 2 nucleoside analog reverse-transcriptase inhibitors (NRTI) plus 1 non-nucleoside analog reverse-transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) for more than 17 years. There are several unresolved issues, notably the toxocity associated with NRTI, especially thymidine analogs, and the possibility of cross resistance, which may affect subsequent treatment. The development of new antiretroviral drugs with simpler dosing regimens and lower toxicity has led to evaluation of innovative strategies such as dual therapy for initial ART in treatment-naive, with the aim of preventing long-term toxicity and increasing treatment adherence. Despite encouraging results, some combinations have proven unsatisfactory. The strategies with favorable results to date consist of twice-daily lopinavir/ritonavir (LPV/r)-based regimens, those in the PROGRESS (LPV/r + raltegravir) and GARDEL (LPV/r + lamivudine) trials, and the combination of darunavir and raltegravir (NEAT 001 trial), although the latter observed a higher tendency (statistically nonsignificant) to virological failure in the dual combination arm. These trials were based on the use of NRTI-sparing regimens consisting of 2–3 fully- active agents for highly-active ART in treatment-naïve HIV-positive patients. Recent studies provide evidence supporting the use of NRTI-sparing regimens in HIV-infected patients with failure to an initial NNRTI-based ART regimen. The present review will discuss only LPV/r-based innovative strategies in initial ART regimens.

BMS-986001 is Effective Treatment for HIV-1-Infected Subjects

BMS-986001 is a novel nucleoside analog reverse-transcriptase inhibitor that, in higher doses, demonstrated comparable efficacy to tenofovir in treatment-naïve HIV-1-infected subjects. This article presents the results of this phase 2b randomized dose trial (active controlled, blinded to BMS-986001) with worldwide recruitment.

Vitamin E concentrations in adults with HIV/AIDS on highly active antiretroviral therapy.

HIV/AIDS patients are probably more predisposed to vitamin E deficiency, considering that they are more exposed to oxidative stress. Additionally, there are an extensive number of drugs in the highly active antiretroviral therapy (HAART) regimens that may interfere with vitamin E concentrations. The objective of this study was to compare serum concentrations of alpha-tocopherol in 182 HIV/AIDS patients receiving different HAART regimens. The patients were divided into three groups according to regimen: nucleoside analog reverse-transcriptase inhibitors (NRTIs) + non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs); NRTIs + protease inhibitors + ritonavir; NRTIs + other classes. Alpha-tocopherol was assessed by high-performance liquid chromatography. Multiple linear regression analysis was used to evaluate the effects of HAART regimen, time of use, and compliance with the regimen on alpha-tocopherol concentrations. Alpha-tocopherol concentrations were on average 4.12 μmol/L lower for the NRTIs + other classes regimen when compared to the NRTIs + NNRTIs regimen (p = 0.037). A positive association (p < 0.001) was observed between alpha-tocopherol and cholesterol concentrations, a finding due, in part, to the relationship between liposoluble vitamins and lipid profile. This study demonstrated differences in alpha-tocopherol concentrations between patients using different HAART regimens, especially regimens involving the use of new drugs. Long-term prospective cohort studies are needed to monitor vitamin E status in HIV/AIDS patients since the beginning of treatment.

Prophylactic and therapeutic effect of AZT/3TC in RT-SHIV infected Chinese-origin rhesus macaques

BackgroundThe precise efficacy of nucleoside analogue reverse-transcriptase inhibitors (NRTIs) in preventing and inhibiting virus replication remains unknown in RT-SHIV infected Chinese-origin rhesus macaques (Ch RM).FindingsCh RM were inoculated intravenously with 200 TCID50 RT-SHIV and treated by gavage with NRTIs (20 mg AZT and 10 mg 3TC twice per day) for four consecutive weeks beginning at one hour, on day 217 or 297 post inoculation, respectively. Treatment with AZT/3TC inhibited transiently RT-SHIV replication during chronic infection, but did not significantly affect peripheral blood CD4+ T cells in macaques. Treatment with AZT/3TC at 1 hour post infection prevented RT-SHIV infection in two out of four animals during the 120-day observation period.ConclusionsTherefore, the Ch RM model with RT-SHIV infection can be used to evaluate the efficacy of new NRTIs.

New-Onset Saquinavir-Induced Diabetes

Saquinavir is an antiviral agent FDA- approved for the treatment of HIV. It inhibits HIV protease, a crucial enzyme for the HIV life cycle that cleaves viral polypeptides into essential proteins. When used in combination with nucleoside analog reverse-transcriptase inhibitors, protease inhibitors are highly effective in reducing HIV viral loads (1,2). In general, saquinavir is safe and well tolerated. Long-term exposure to protease inhibitors is associated with moderate hyperglycemia and insulin resistance in a minority of patients (3). We here report saquinavir as a causing agent of acutely developed extreme hyperglycemia in an HIV patient. A 35-year-old HIV-infected male originating from Ghana presented with a hyperosmolar, hyperglycemic syndrome (glucose 48 mmol/L). He had been diagnosed with HIV-1 infection 2 years previously, with tenofovir, …

Current treatment methods for combination antiretroviral therapy-induced lipoatrophy of the face

Combination antiretroviral therapy (CART) reduces the mortality and morbidity in HIV-infected patients. However, facial lipoatrophy (FLA) is one of the well-known side-effects of this treatment and subsequently imposes major problems for HIV-infected patients. In the last decade, ample experience has been obtained with both local therapeutic options as well as possible systemic treatment options. Soft tissue fillers are a relatively simple and efficient treatment option for FLA. Especially, the biodegradable semi-permanent fillers combine a good effect with durability and an acceptable safety profile. The best way to prevent or restrict the development of FLA remains the exclusion of thymidine analogue nucleoside reverse-transcriptase inhibitors from the CART schedule.

Allogene Stammzelltransplantation bei Akuter Myeloischer Leukämie und HIV-Infektion – Fall 3/2012

A 27-year-old male patient with a past medical history of HIV presented with acute myeloid leukemia for allogeneic hematopoietic stem cell transplantation (HSCT). Highly active anti-retroviral therapy suppressed the viral load below detection threshold. There were no contraindications for allogeneic HSCT. Myeloablative conditioning consisted of total body irradiation and cyclophosphamide. Anti-thymocyte globulin, tacrolimus and mycophenolate mofetil were used for immunosuppression. Combined anti-retroviral therapy (nucleoside and nucleotide analog reverse-transcriptase inhibitor, boostered protease inhibitor, maraviroc and raltegravir) was maintained for allogeneic HSCT and viral load remained below detection threshold. No graft-versus-host disease or serious infectious complications occurred. The patient showed good graft function with stable hematopoiesis. Localized Kaposi's sarcoma was diagnosed six months after allogeneic HSCT and treated successfully with surgical excision and reduction of immunosuppression. Almost one year after allogeneic HSCT, the CD4+ cell count is rising and viral load remains below detection threshold with combined anti-retroviral therapy. Allogeneic HSCT can be safely performed in HIV positive patients. Kaposi's sarcoma is a rare event after allogeneic HSCT and linked to strong immunosuppression.