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BACKGROUND: Outside of randomized controlled trials (RCTs), there are limited data regarding the acceptability of injectable long-acting cabotegravir + rilpivirine (LA-CAB+RPV) among persons living with HIV (PLWH). To evaluate acceptability, we describe participant-reported outcomes (PRO) of LA-CAB+RPV among a population underrepresented in RCTs. SETTING: Ruth M. Rothstein Core Center (CORE), large urban HIV clinic in Chicago, Illinois, USA. METHODS: We interviewed PLWH prescribed LA-CAB+RPV who receive primary care at CORE. PRO endpoints included treatment satisfaction, tolerability of injections, reasons for switching to LA-CAB+RPV, and unexpected effects of LA-CAB+RPV. Mean and standard deviations (mean±SD) and proportions (%) are reported. RESULTS: Among respondents (N=150), 67% identified as Non-Hispanic Black, 24% Hispanic, 56% male; the average age was 43 years (SD:13.2), and 37% were ≥50 years old. Most respondents (93%) completed ≥3 injection appointments at the time of interview. The most common reasons for switching to LA-CAB+RPV were no longer wanting to take pills (89%) and trouble taking their pills daily (58%). Treatment satisfaction was high (6.7±0.5 out of 7). Two-thirds (61%) reported an unexpected aspect of their life improved. Pain from injections was common (98%), with a mean pain score of 4.3 out of 10. Among those reporting pain, half (47%) reported pain decreased after initial injection. Among participants reporting pain score >6 (n=36), most (78%) reported no improvement since initial injection. CONCLUSIONS: We found high treatment satisfaction with LA-CAB+RPV in a diverse population. Participants reported moderate injection pain, which improved with time. Results suggest injectable LA-CAB+RPV will be met with acceptability across diverse participant populations.
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HIV integrase strand transfer inhibitors (INSTI) are considered well tolerated with few treatment-limiting adverse effects. However, emerging data from clinical trials has identified excessive weight gain possibly due to INSTI alone or with tenofovir alafenamide as a new and possible long-term complication of combination antiretroviral therapy (cART). Identifying who is at greatest risk and whether the unintended weight gain is reversible remain unanswered questions. We report a return to baseline weight after switching back to tenofovir disoproxil/emtricitabine/efavirenz (Atripla®) in a woman who had profound weight gain due to tenofovir alafenamide/emtricitabine/cobicistat/elvitegravir (Genvoya®).
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Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Adulto , Alanina , Fármacos Anti-HIV/uso terapêutico , Cobicistat/uso terapêutico , Combinação de Medicamentos , Emtricitabina/uso terapêutico , Feminino , HIV-1 , Humanos , Quinolonas , Tenofovir/análogos & derivados , Aumento de PesoRESUMO
A potential drug-drug interaction exists between divalent and trivalent cations (Ca2+, Fe3+, Mg2+, Al3+, Zn2+) and HIV-1 integrase strand transfer inhibitors (INSTIs). There are limited case reports describing the clinical significance of this potential interaction and none to our knowledge identifying zinc co-administration with INSTIs. In this report we present a patient taking bictegravir/emtricitabine/tenofovir alafenamide who became viremic after ingesting zinc and calcium supplements and later was able to obtain virologic re-suppression after discontinuing supplements. This case represents a potential significant drug interaction between a commonly prescribed antiretroviral drug class and readily available over-the-counter divalent cation products.
RESUMO
Selection of an appropriate antiretroviral regimen for the patient infected with human immunodeficiency virus can be challenging, as various considerations must be taken into account including viral resistance mutations, patient comorbidities, drug interactions, and the potential for drug-related adverse effects and toxicities. Treatment is further complicated when a clinical scenario arises requiring an alteration in the dosage form. Factors ranging from dysphagia to administration through an enteral feeding tube can affect decisions regarding antiretroviral dosage forms. Limited pharmacokinetic data exist regarding the alteration of antiretroviral medications from their original form. Bioavailability may vary substantially between dosage forms, which can lead to unpredictable drug concentrations. Supratherapeutic or subtherapeutic antiretroviral drug concentrations can result in increased toxicity, virologic failure, or the emergence of drug resistance. We performed a systematic literature search to review the available antiretroviral literature on the modification of solid dosage forms as well as alternative routes of administration of oral antiretroviral agents and their application to clinical practice.
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Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Transtornos de Deglutição/complicações , Interações Medicamentosas , Farmacorresistência Viral , Nutrição Enteral/métodos , HumanosRESUMO
BACKGROUND: Tenofovir associated nephrotoxicity (TDFN) is well recognized. This study describes the trend of renal function recovery and virologic consequences after cessation of tenofovir (TDF) for suspected TDFN. METHODS: This was a retrospective chart review of 241 patients who underwent HLA-B*5701 allele testing between January 2007-December 2010. Demographics and clinical characteristics were compared at baseline, 3, 6, and 12 month between patients that continued and discontinued TDF. Factors associated with renal function recovery were assessed by multivariable logistic regression. RESULTS: Eighty patients were identified with TDFN; 84% male, 74% African American (AA) with a median age of 55 years, and median length of TDF use for 122 weeks. Renal recovery at 12 months differed in those who stopped versus (vs.) continued TDF (83% vs. 57% p=0.03). In a crude analysis, baseline chronic kidney disease was negatively associated with renal recovery (p=0.01). An adjusted analysis showed that those who stopped TDF had 3.76 higher odds of renal recovery compared to those who did not stop TDF (95% CI: 1.26-11.27, p=0.02). There were no significant differences in virologic response after switching TDF to an alternative agent. CONCLUSION: In this mostly AA male population with suspected TDFN, discontinuation of TDF was strongly associated with renal function recovery without affecting viral suppression.
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Venous thrombosis is a well-described complication of thalidomide therapy in patients with multiple myeloma (MM). However, an association between thalidomide use and thrombosis in HIV-positive patients has not been previously described. We present the case of a 48-year-old HIV-positive man who developed a deep venous thrombosis while on thalidomide for the treatment of severe aphthous ulcers. We review the management of severe aphthous disease and the potential adverse effects of thalidomide therapy. We examine the association between thalidomide and thrombosis in patients with MM and discuss how the same relationship may or may not exist in HIV-positive patients. Although the strength of the association between thalidomide use and thrombosis in HIV-positive patients being treated for aphthous disease remains unclear, HIV providers should be aware of the potential risk of thrombosis in all patients receiving thalidomide.
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Soropositividade para HIV/complicações , Imunossupressores/efeitos adversos , Estomatite Aftosa/tratamento farmacológico , Talidomida/efeitos adversos , Trombose Venosa/induzido quimicamente , Fármacos Anti-HIV/uso terapêutico , Soropositividade para HIV/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Estomatite Aftosa/etiologia , Talidomida/uso terapêuticoRESUMO
We describe a 55-year-old HIV-1-infected male who developed severe dyslipidaemia (total cholesterol 600 mg/dl, triglycerides >5,000 mg/dl, high density lipoprotein <5 mg/dl) after raltegravir was added to his lopinavir/ritonavir-containing regimen. To our knowledge, this is the first reported case of severe dyslipidaemia associated with the addition of raltegravir to a lopinavir/ritonavir-based regimen, suggestive of a possible drug interaction. The lipid profile quickly normalized following discontinuation of lopinavir/ritonavir and continuation of raltegravir, suggesting that lopinavir/ritonavir was the primary driver for the adverse event. With increasing interest in nucleoside-sparing regimens, knowledge of clinically significant adverse events such as this is important for HIV clinicians when selecting regimens for patients with highly resistant virus or drug tolerability issues.
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Dislipidemias/induzido quimicamente , Infecções por HIV/complicações , Inibidores da Protease de HIV/efeitos adversos , Lopinavir/efeitos adversos , Pirrolidinonas/efeitos adversos , Ritonavir/efeitos adversos , HDL-Colesterol/sangue , Interações Medicamentosas , Quimioterapia Combinada , Dislipidemias/patologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Inibidores da Protease de HIV/uso terapêutico , HIV-1/patogenicidade , Humanos , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pirrolidinonas/uso terapêutico , Raltegravir Potássico , Ritonavir/uso terapêutico , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
BACKGROUND: In the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL) is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL. METHODS: During December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases. RESULTS: Five cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years). All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5) versus controls (n = 73) were 44 vs.117 cells/mm3 (p = 0.09) and 5.2 vs. 4.2 log10 (p = 0.06), respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5) vs. 74 (n = 50)(p = 0.284). Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5) vs. 1.94 (n = 50)(p = 0.045). CONCLUSIONS: An unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors associated with rapid development of NHL warrants further investigation.
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We determined rates of achieving the American Diabetes Association goals among human immunodeficiency virus (HIV)-infected diabetic patients. American Diabetes Association goals (for hemoglobin A1c, blood pressure, and lipid levels) were defined by 2008 American Diabetes Association guidelines. HIV-infected diabetic patients achieved American Diabetes Association goals at rates similar to those in general medicine clinic patients. A multidisciplinary approach is needed to improve diabetes management in HIV clinics.
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Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Hemoglobinas Glicadas/análise , Infecções por HIV/complicações , Lipídeos/sangue , Atenção Primária à Saúde/normas , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Pressão Sanguínea , Diabetes Mellitus Tipo 2/sangue , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde/estatística & dados numéricos , Estudos Retrospectivos , Sociedades Médicas , Estados UnidosRESUMO
INTRODUCTION: To explore whether an assay change was responsible for an increasing proportion of patients with undetectable HIV viral loads at our urban HIV clinic, we selected highly stable patients, examining their viral loads before and after changing assays. We compared the proportion with detectable viremia during RT-PCR vs. bDNA periods. METHODOLOGY/PRINCIPAL FINDINGS: We selected patients with > or =1 viral loads assessed during both RT-PCR and bDNA periods. We included patients with stable CD4 counts, excluding patients with viral loads > or =1,000 copies/ml or any significant changes in therapy. Out of 4500 clinic patients, 419 patients (1588 viral loads) were included. 39% of viral loads were reported as detectable by RT-PCR vs. 5% reported as detectable by bDNA. The mean coefficient of variation was higher before vs. after assay change. We found an odds' ratio of 16.7 for having a viral load >75 copies/ml during the RT-PCR vs. bDNA periods. DISCUSSION: These data support previous reports, suggesting that bDNA may more reliably discriminate between viral suppression and low level viremia in stable patients on therapy. Low-level viremia, noted more with RT-PCR, may promote unneeded testing, while differences in viral load reliability may impact antiretroviral trial and quality assurance endpoints. Commonly used plasma separator tubes may differentially affect RT-PCR and bDNA results.
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Ensaio de Amplificação de Sinal de DNA Ramificado/métodos , Infecções por HIV/diagnóstico , HIV-1/genética , RNA Viral , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Carga Viral/métodos , Viremia/diagnóstico , Adulto , Antígenos CD4/biossíntese , Estudos de Coortes , Feminino , Infecções por HIV/genética , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Viremia/genéticaRESUMO
We sought to determine the utility of repeat genotypic resistance testing (GRT) and the clinical response in HIV-1-infected patients with known resistance to three of the major classes of antiretroviral drugs. The HIV-1 genetic sequences for 20 patients who had high-level 3 class resistance demonstrated on a prior GRT (3C-GRT 1) measured during the period from November 1, 2000 through July 1, 2004 were retrospectively evaluated. At the time of 3C-GRT 1, the median CD4 count and HIV-1 RNA viral load were 168 cells/mm(3) and 4.5 log copies per milliliter, respectively. The median time to the second GRT (3C-GRT 2) was 17 months. At that time, the median CD4 count and VL were 140 cells/mm(3) and 4.9 log copies per milliliter (p = 0.8 and p = 0.12, respectively). On 3C-GRT 2, all patients retained essentially identical mutations, with the exception of the loss of the M184V mutation in 6 patients. After 3C-GRT 2, all patients continued on protease inhibitor-containing highly active antiretroviral therapy (HAART) regimens. At 24 weeks after 3C-GRT 2, there was no significant change in CD4 count or HIV-1 RNA viral load (p = 0.68 and p = 0.30, respectively). Repeat GRT in patients with documented high-level 3 class resistance does not provide new or clinically useful information. Under continued antiretroviral selective pressure, the viral genetic sequences in this patient population remained stable. In addition, continuing HAART regimens containing protease inhibitors appeared to forestall further immunological and virologic deterioration in patients with multiple resistance mutations. Providers should focus on obtaining access to combinations of novel agents for patients with 3 class resistance rather than repeated GRT.
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Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , HIV-1/genética , Inibidores da Transcriptase Reversa/farmacologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/imunologia , Infecções por HIV/virologia , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , HIV-1/enzimologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , RNA Viral/sangue , Inibidores da Transcriptase Reversa/uso terapêutico , Falha de Tratamento , Resultado do TratamentoRESUMO
The Havana trial, a randomized, prospective study, demonstrated that expert interpretation of genotypic resistance test (GRT) results improved virological outcomes in human immunodeficiency virus type 1 (HIV-1)-infected patients for whom highly active antiretroviral therapy (HAART) was failing. The impact of expert advice in routine clinical practice is unknown. We retrospectively evaluated the virological outcomes of 74 patients for whom HAART was failing and whose clinical providers accepted or rejected HAART regimens recommended by an expert panel who routinely reviewed GRT results. Fifty (68%) of 74 patients received regimens recommended by the expert panel ("advice accepted" [AA]), and 24 patients (32%) received regimens per the clinician's preference ("advice rejected" [AR]). After 24 weeks, AA and AR groups had median decreases in the plasma HIV-1 RNA viral load of 2.6 and 1.3 log(10) copies/mL, respectively (P=.0001). Twenty-six (52%) of 50 patients in the AA group and 5 (21%) of 24 patients in the AR group had a plasma HIV-1 RNA viral load of <50 copies/mL (P=.01). Consideration should be given to enlisting expert assistance in the interpretation of GRT results in routine clinical practice.