Hepatic safety of maraviroc in patients with HIV-1 and hepatitis C and/or B virus: 144-week results from a randomized, placebo-controlled trial.

BACKGROUND: In the primary 48-week analysis of a hepatic safety trial in patients with HIV-1 coinfected with HBV and/or HCV, maraviroc-containing treatment regimens were not associated with increased hepatotoxicity. METHODS: In this randomized, double-blind, placebo-controlled, multicentre study, patients received maraviroc twice daily (n=70) or placebo (n=67) with concomitant antiretroviral therapy for 144 weeks (Clinicaltrials.gov identifier, NCT01327547). The primary end point was the proportion of patients with protocol-defined Grade 3/4 alanine aminotransferase (ALT) abnormalities through week 48. Key secondary end points included 144-week analysis of Grade 3/4 ALT abnormalities and liver fibrosis by enhanced liver fibrosis (ELF) testing, hepatic elastography and an optional biopsy substudy. RESULTS: Through 144 weeks of treatment, two (maraviroc) and three (placebo) patients met the protocol-defined Grade 3/4 ALT end point. Similar to the 48-week results, there were no statistically significant differences between groups in change from baseline in ELF or hepatic elastography. However, decreased elastography scores were noted in the maraviroc group. Blinded pathologist review suggested that 2 of 11 paired biopsies (both on maraviroc) showed signs of decreased fibrosis. One (maraviroc) and two (placebo) patients experienced treatment-related hepatobiliary adverse events (AEs). Five patients in the maraviroc group discontinued because of treatment-related AEs versus three in the placebo group. One death in the maraviroc group and two deaths in the placebo group were reported. CONCLUSIONS: Use of maraviroc did not increase hepatotoxicity in this population through 144 weeks. Further investigation regarding possible beneficial effects of maraviroc on liver fibrosis may be warranted.

Combination of long-acting HIV fusion inhibitor albuvirtide and LPV/r showed potent efficacy in HIV-1 patients.

BACKGROUND: Long acting antiretroviral drugs represent a promising approach for chronic treatment of HIV infection. Here, we study the efficacy and safety of albuvirtide (ABT), an HIV-1 fusion inhibitor with a half life of 11-12 days in human. METHODS: ABT was evaluated in a 7-week, open-label and randomized trial, combining with LPV/r. Twenty HIV-1-infected adults were assigned to two dose groups, receiving ABT (160 or 320 mg) given weekly and LPV/r given twice daily. RESULTS: At week 7, the decline of HIV-1 RNA from baseline was 1.9 (1.3-2.3) log10 and 2.2 (1.6-2.7) log10 copies/ml, and suppression of HIV-1 RNA to below 50 copies/ml was achieved in 11.1 % (1/9) and 55.6 % (5/9) patients, for the 160 and 320 mg dose group respectively. CONCLUSION: A clear dose-efficacy correlation of ABT was demonstrated. ABT combining with LPV/r is a promising two-drug regimen to be tested in larger patient population.

Maraviroc: a review of its use in HIV infection and beyond.

The human immunodeficiency virus-1 (HIV-1) enters target cells by binding its envelope glycoprotein gp120 to the CD4 receptor and/or coreceptors such as C-C chemokine receptor type 5 (CCR5; R5) and C-X-C chemokine receptor type 4 (CXCR4; X4), and R5-tropic viruses predominate during the early stages of infection. CCR5 antagonists bind to CCR5 to prevent viral entry. Maraviroc (MVC) is the only CCR5 antagonist currently approved by the United States Food and Drug Administration, the European Commission, Health Canada, and several other countries for the treatment of patients infected with R5-tropic HIV-1. MVC has been shown to be effective at inhibiting HIV-1 entry into cells and is well tolerated. With expanding MVC use by HIV-1-infected humans, different clinical outcomes post-approval have been observed with MVC monotherapy or combination therapy with other antiretroviral drugs, with MVC use in humans infected with dual-R5- and X4-tropic HIV-1, infected with different HIV-1 genotype or infected with HIV-2. This review discuss the role of CCR5 in HIV-1 infection, the development of the CCR5 antagonist MVC, its pharmacokinetics, pharmacodynamics, drug-drug interactions, and the implications of these interactions on treatment outcomes, including viral mutations and drug resistance, and the mechanisms associated with the development of resistance to MVC. This review also discusses available studies investigating the use of MVC in the treatment of other diseases such as cancer, graft-versus-host disease, and inflammatory diseases.

Five-year safety evaluation of maraviroc in HIV-1-infected treatment-experienced patients.

BACKGROUND: Maraviroc is unique among approved antiretroviral drugs in targeting the host-cell chemokine coreceptor type-5 receptor. With its novel mechanism of action, we sought to describe the 5-year safety profile of maraviroc. METHODS: Two large phase 3 studies of maraviroc enrolled HIV-infected treatment-experienced patients and followed them up for 5 or more years. Survival and selected clinical end points were identified and assessed. RESULTS: A total of 938 enrolled patients received maraviroc-containing regimens. Rates of death and selected clinical events (eg, hepatic failure, malignancy, and myocardial infarction) were low during follow-up. CONCLUSIONS: Maraviroc was generally safe in treatment-experienced participants for >5 years.

A reduced grade of liver fibros-steatosis after raltegravir, maraviroc and fosamprenavir in an HIV/HCV co-infected patient with chronic hepatitis, cardiomyopathy, intolerance to nelfinavir and a marked increase of serum creatine phosphokinase levels probably related to integrase inhibitor use / Grado reducido de fibroesteatosis tras la administración de raltegravir, maraviroc y fosamprenavir en un paciente co-infectado de VIH/VHC con hepatitis crónica, cardiomiopatía, intolerancia al nelfinavir y un aumento pronunciado de los niveles de creatina fosfoquinasa sérica probablemente debido al uso del inhibidor de la integrasa

The use of new antiretroviral drugs in HIV infection is particularly important in patients with intolerance or resistance to other antiretroviral agents. Raltegravir and maraviroc represent new, important resources in salvage regimens. A reduced grade of liver fibro-steatosis after a combination of raltegravir and maraviroc (second-line) has not been studied and the mechanism by which these new drug classes induced a marked reduction of grade of liver diseases is currently unknown. In the present case report, nested in an ongoing multicentre observational study on the use of new antiretroviral inhibitors in heavy treatment-experienced HIV patients, we evaluated the correlation between a "short therapeutic regimen" raltegravir, maraviroc and fosamprenavir and liver diseases. The aim of this report is to describe the use of a three-drug regimen based on two novel-class antiretroviral agents (raltegravir and maraviroc) plus the protease inhibitor fosamprenavir, in an experienced HIV-infected patient with chronic progressive hepatitis C complicated by liver fibrosis; an overwhelming increased serum creatine kinase level occurred during treatment, and is probably related to integrase inhibitor administration. At present no information is available regarding this correlation.

El uso de nuevos medicamentos antiretrovirales para la infección por VIH es particularmente importante en los pacientes con intolerancia o resistencia a otros agentes antiretrovirales. Raltegravir (RTV) y maraviroc (MRV) representan nuevos e importantes recursos en las terapias de salvamento. Un grado reducido de fibroesteatosis hepática después de una combinación de raltegravir y maraviroc (terapia de segunda línea) no ha sido estudiado, y el mecanismo por el cual estas nuevas clases de droga indujeron una marcada reducción de grado de las enfermedades hepáticas se desconoce hasta el momento. Como parte de la realización en curso de un estudio observacional multicentro acerca del uso de nuevos inhibidores antiretrovirales en pacientes de VIH altamente experimentados en el tratamiento, en el presente reporte de caso se evalúa la correlación entre un "régimen terapéutico corto" (raltegravir, maraviroc y fosamprenavir) y las enfermedades del hígado. El objetivo de este reporte es describir el uso de un régimen de tres medicamentos - basado en dos agentes antiretrovirales de nuevo tipo (raltegravir y maraviroc) además del fosamprenavir inhibidor de la proteasa - en un paciente de VIH experimentado. El paciente también sufre de hepatitis C evolutiva, progresiva, crónica, complicada por fibrosis hepática. Durante el tratamiento, se produjo un aumento extraordinario del nivel de creatina quinasa sérica, el cual probablemente esta relacionado con la administración del inhibidor de la integrasa. Actualmente no hay información disponible con respecto a esta correlación.

Enfuvirtide and cutaneous injection-site reactions.

Enfuvirtide belongs to a newer class of antiretroviral (ARV) agents called fusion inhibitors for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Enfuvirtide blocks attachment, binding, and entry of the viral capsid into the host CD4+ cell. Administration is only available subcutaneously in a twice-daily regimen particularly for those patients who have previously failed more than one ARV regimen. Common side effects of enfuvirtide administration include fatigue, insomnia, nausea, and diarrhea; however, injection-site reactions are the most common side effect and present in nearly all individuals undergoing treatment. The spectrum of cutaneous manifestations ranges from little to no reaction to cysts, nodules, induration, or sclerodermalike lesions. These reactions are mostly variants of iatrogenically induced hypersensitivity and are self-limited.

Enfuvirtide injection site reactions: a clinical and histopathological appraisal.

BACKGROUND/OBJECTIVES: Enfuvirtide was the first of a new class of antiretroviral agents termed 'fusion inhibitors' used for the treatment of HIV-1 infection. Enfuvirtide is administered subcutaneously and injection site reactions (ISR) are commonplace (98%). The aim of this study was to analyse in detail the histopathological changes associated with striking ISR seen in four patients. METHODS: Biopsies were obtained at various times post-injection and were reviewed histologically. The changes in epidermal, dermal and subcutaneous connective tissue and the presence and nature of the inflammatory cellular infiltrate were noted. An immunohistochemical assessment was undertaken. RESULTS: All biopsy specimens demonstrated striking changes in the dermal connective tissue. Alteration in collagen was the most prominent feature and resembled a morphoea/scleroderma-like process. These changes persisted well beyond cessation of enfuvirtide (>1 year). The relative populations of dermal dendritic cells (DDC) (types 1 (Factor XIIIa) and 2 (CD34+)) were analysed and a reciprocal relationship between DDC subpopulations was observed akin to that observed in other sclerosing and fibrosing conditions. CONCLUSION: This study details histopathological changes associated with enfuvirtide ISR. We postulate that changes in DDC populations may contribute to the pathogenesis of the sclerotic process observed with enfuvirtide ISR.

Efficacy and safety of maraviroc versus efavirenz, both with zidovudine/lamivudine: 96-week results from the MERIT study.

BACKGROUND: The MERIT study evaluated maraviroc versus efavirenz, both with zidovudine/lamivudine, in treatment-naïve patients with CCR5-tropic (R5) HIV-1. Post hoc analyses previously assessed week 48 outcomes in patients rescreened with R5 virus by a more sensitive tropism assay. METHODS: Week 96 efficacy (post hoc, n = 614) and safety (n = 721) were assessed. RESULTS: Proportions of subjects <50 copies/mL (58.8% maraviroc, 62.7% efavirenz) and time to loss of virologic response (TLOVR) responders (<50 copies/mL: 60.5% vs 60.7%) were similar. Maraviroc recipients had greater CD4 increases (+ 212 vs + 171 cells/mm(3)) and fewer adverse event discontinuations (6.1% vs 15.5%), malignancies, and category C events. CONCLUSION: Week 96 data confirm week 48 observations in MERIT.

Fuzeon-induced collagenophagic granuloma: a peculiar granulomatous injection site reaction to Fuzeon--a case report and review of literature.

Enfuvirtide (ENF, T-20, or Fuzeon [Hoffman-La Roche Inc, Nutley, NJ, and Trimeris, Inc, Durham, NC]) is an HIV-1 fusion inhibitor and is the only injectable antiretroviral drug available. Injection site reactions (ISRs) are the most frequently reported adverse events, occurring in about 98% of patients. A granuloma annulare-like granulomatous ISR has been reported. We report a granulomatous ISR that is different from granuloma annulare and granuloma annulare-like reaction because it is rich in multinucleated giant cells engulfing altered collagen. We call this type of ISR a collagenophagic granuloma. Most previous reports-with the exception of 1 report-about ISRs with ENF treatment have used punch biopsies, which lack the depth to analyze the reticular dermis and subcutaneous tissue and, therefore, may have missed ISRs, which look like granuloma annulare, and the collagenophagic granulomatous reaction.

Maraviroc first-line therapy for HIV infection. Too risky.

First-line treatment for HIV infection currently comprises a combination of antiretroviral drugs, including a non-nucleoside reverse transcriptase inhibitor such as efavirenz, or one or two protease inhibitors.The choice is based on the results of initial clinical trials of antiretroviral drugs with morbidity and mortality endpoints, and, since the 1990s, on trials with surrogate markers (viral load and the CD4+ T lymphocyte count). Maraviroc is the only CCR5 antagonist currently on the market. Drugs belonging to this class are designed to prevent HIV entry into CD4 T lymphocytes. Maraviroc is reserved for patients with multiple treatment failure, but has also been proposed for first-line treatment. Clinical evaluation of maraviroc in first-line treatment is limited to a single comparative trial designed to show the virological and immunological "non-inferiority" of the maraviroc + zidovudine + lamivudine combination versus efavirenz + zidovudine + lamivudine, after 96 weeks of treatment, in 721 patients with CCR5-tropic HIV strains. A more sensitive version of the test used to determine CCR5 tropism became available during the trial, leading to the exclusion of 107 patients who were infected by strains capable of using other coreceptors. This trial fails to answer important questions regarding the adverse effects of maraviroc, such as hepatotoxicity, infections, cancer, and cardiovascular disorders. Tests used to identify exclusively CCR5-tropic HIV strains are difficult to implement and their results are unreliable. This means that some patients in whom maraviroc will not be effective may receive this drug, and will thus be at risk of developing viral resistance to other drugs in their antiretroviral regimen. In practice, first-line use of maraviroc is imprudent, as it depends on a test of uncertain reliability. Furthermore, there is no evidence to suggest that maraviroc combination therapy has a better risk-benefit balance than regimens with well-documented and long established efficacy.

A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1.

BACKGROUND: Maraviroc, a CCR5 antagonist, is active against R5 but not X4 or dual- or mixed-tropic strains of human immunodeficiency virus type 1 (HIV-1). A phase 2b study was conducted to determine the safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced patients infected with dual- or mixed-tropic HIV-1. METHODS: Treatment-experienced patients with an HIV-1 RNA level 5000 copies/mL who had received 3 classes of drugs and/or were infected with virus resistant to 2 drug classes and were infected with non-R5 HIV-1 were randomized to receive optimized background therapy plus maraviroc (once or twice daily) or placebo. The primary end point was change in HIV-1 RNA level from baseline to 24 weeks. RESULTS: Among 167 patients infected with dual- or mixed-tropic HIV-1, baseline mean HIV-1 RNA levels were >5 log(10) copies/mL and median CD4(+) cell counts were <50 cells/microL. From baseline to 24 weeks, patients who received placebo demonstrated a mean decrease in HIV-1 RNA levels of 0.97 log(10) copies/mL, compared with mean decreases of 0.91 and 1.20 log(10) copies/mL for those who received maraviroc once (P =.83) or twice (P +.38) daily, respectively. Mean increases in CD4(+) cell counts from baseline were 36 cells/microL for patients who received placebo, 60 cells/microL among patients who received maraviroc once daily, and 62 cells/microL among patients who received maraviroc twice daily. The incidences of serious adverse events were similar among groups. CONCLUSIONS: In this exploratory study involving extensively treatment-experienced patients with advanced, non-R5 HIV-1 infection, neither superiority nor noninferiority was statistically demonstrated for either maraviroc dosage compared with placebo at 24 weeks of treatment. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00098748 .

Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component.

To prevent sexually transmitted HIV, the most desirable active ingredients of microbicides are antiretrovirals (ARVs) that directly target viral entry and avert infection at mucosal surfaces. However, most promising ARV entry inhibitors are biologicals, which are costly to manufacture and deliver to resource-poor areas where effective microbicides are urgently needed. Here, we report a manufacturing breakthrough for griffithsin (GRFT), one of the most potent HIV entry inhibitors. This red algal protein was produced in multigram quantities after extraction from Nicotiana benthamiana plants transduced with a tobacco mosaic virus vector expressing GRFT. Plant-produced GRFT (GRFT-P) was shown as active against HIV at picomolar concentrations, directly virucidal via binding to HIV envelope glycoproteins, and capable of blocking cell-to-cell HIV transmission. GRFT-P has broad-spectrum activity against HIV clades A, B, and C, with utility as a microbicide component for HIV prevention in established epidemics in sub-Saharan Africa, South Asia, China, and the industrialized West. Cognizant of the imperative that microbicides not induce epithelial damage or inflammatory responses, we also show that GRFT-P is nonirritating and noninflammatory in human cervical explants and in vivo in the rabbit vaginal irritation model. Moreover, GRFT-P is potently active in preventing infection of cervical explants by HIV-1 and has no mitogenic activity on cultured human lymphocytes.

Short communication safety, tolerability and pharmacokinetics of enfuvirtide administered by a needle-free injection system compared with subcutaneous injection.

BACKGROUND: Injection site reactions (ISRs) can present a challenge to patients when using enfuvirtide (ENF). This study compared ISRs associated with use of a needle-free injection device (NFID) with those associated with a standard 27-gauge half-inch needle/syringe (NS). METHODS: In this single-blind, crossover study, 58 ENF-naive participants were randomized to self-administer ENF with the NFID for 4 weeks (followed by 4 weeks using NS) or with the NS for 4 weeks (followed by 4 weeks using the NFID). A primary composite endpoint of painful ISR was defined as the combination of grade 1-3 ongoing pain plus either associated grade 3-4 (> or =25 mm) induration or grade 2-4 nodules/cysts (>20 mm). An ISR summary score described ISR frequency/severity. Self-reported device preference was also evaluated at baseline and at study completion. RESULTS: Fewer participants using NFID experienced the primary composite endpoint of painful ISRs (10/28; 35.7%) compared with NS (20/28; 71.4%) (P=0.004). There was a trend towards a reduced incidence/severity of ISR signs and symptoms with NFID, with significant reductions seen in pain/discomfort and pruritus (P<0.05 and P<0.01, respectively). At the end of the study, most participants (22/25; 88%) expressed a preference for NFID. Haematoma was the sole NFID-related serious adverse event, but this did not lead to discontinuation. CONCLUSIONS: Compared with a standard NS, use of an NFID to administer ENF was associated with a substantially lower incidence of painful ISRs, was generally safe and well-tolerated, and was preferred by most participants in the study.

Raltegravir: new Drug. Alternative to enfuvirtide/darunavir in multidrug-resistant HIV.

(1) HIV-infected patients who have exhausted most existing antiretroviral treatment options benefit when enfuvirtide or darunavir is added to an optimised multidrug regimen based on the resistance profile; (2) Raltegravir is the first HIV integrase inhibitor to arrive on the market. It was authorised in 2007 in the European Union for patients with multiple antidrug failure; (3) A dose-finding study and two double-blind placebo-controlled trials showed that when raltegravir is added to an optimised antiretroviral regimen about two-thirds of patients achieve undetectable viral load, compared to about one-third of patients treated with an optimised regimen plus placebo. Data are currently limited to 48 weeks. In contrast, adding raltegravir barely increases the efficacy of treatments already containing enfuvirtide and darunavir. Half of patients in whom treatment failed developed viral resistance to raltegravir during these trials; (4) In previously untreated patients, a double-blind controlled trial showed no statistically significant difference in viral load at 48 weeks between raltegravir/tenofovir/lamivudine and efavirenz/tenofovir/lamivudine, but there were only about 40 patients in each group; (5) The adverse effects of raltegravir are poorly documented. In vitro findings, along with the limited clinical data available, point to a potential risk of autoimmune and lymphoproliferative disorders in the long term. (6) Raltegravir is not metabolised by the cytochrome P450 enzyme system, meaning that it should have fewer pharmacokinetic interactions than darunavir. But raltegravir is sensitive to enzyme inducers, which activate its metabolism; (7) Raltegravir is taken orally, twice a day, either during or between meals; (8) In practice, raltegravir is an option for HIV-infected patients with multiple antiretroviral drug failure and few remaining treatment options. It represents an alternative to the darunavir/enfuvirtide combination, and has the advantage of being more convenient to use. Assessment must continue, however, especially in order to identify long-term adverse effects.

[Secondary effects of treatment with maraviroc and other CCR5 antagonists. Potential impact of the CCR5 blocker]. / Efectos secundarios asociados al tratamiento con maraviroc y otros antagonistas de CCR5. Impacto potencial del bloqueo del receptor CCR5.

Maraviroc is the first inhibitor of CCR5 co-receptors to be marketed as an antiretroviral. The pre-clinical studies and phase III trials have shown that it has a very favourable safety profile. No characteristic adverse effect of maraviroc has been identified. Unlike with aplaviroc, where its clinical development was stopped due to serious hepatoxicity, no increase in liver toxicity has been demonstrated in patients treated with maraviroc even if they are co-infected by hepatotropic virus. Nor was there any evidence of an increase in the incidence of neoplasms or serious infections in patients treated with maraviroc. In a study on naive patients, maraviroc produced nonsignificant changes in total cholesterol, LDL, HDL and triglycerides. Although CCR5 co-receptors play a role in the immune response of the body, it has not been shown whether individuals homozygote for its deletion (delta-32 mutation) have an increased risk of serious infections, with the possible exception of encephalitis due to the West Nile virus. However, long-term follow up is required on patients treated with to be able to rule out any increased susceptibility to infections or neoplasms.

[Conclusions and perspectives. Maraviroc]. / Conclusiones y perspectivas.

This monograph discusses most important aspects Maraviroc, the development and application perspectives of this drug, as well as main questions raised in its use. Maraviroc is the first CCR5 antagonist approved for treating HIV infection. Its imidazopyridine structure interacts with CCR5 and induces a co-receptor conformation that prevents glycoproteins binding to the viral envelope. It has powerful antiviral activity and acts on a wide spectrum of viruses with affinity for this receptor. This situation means that a tropism test has to be done before treatment to define whether the patient is a carrier of R5 variants. Maraviroc is indicated in HIV infected patients who have received previous antiretroviral treatment. It has a low toxicity and, according to preliminary data, a high genetic barrier. The resistance mechanism is associated with changes in the V3 region which allow the virus to recognise the CCR5 co-receptor bound to the Maraviroc molecule. The main cause of treatment failure is the selection of pre-existing X4 strains not detected by the reference test. Maraviroc can be combined with any other antiretroviral on the market or in clinically advanced development. The indication of Maraviroc in the early phases of the infection is not currently recommended and will depend whether it is shown to be inferior when compared other treatments or a benefit in other pathogenic aspects, such as recovery of CD4 lymphocytes or a reduction in viral reservoirs.

Maraviroc (Celsentri) for multidrug-resistant human immunodeficiency virus (HIV)-1.

(1) Maraviroc belongs to a new class of antiretroviral drugs designed to block entry of HIV-1 into CD4+ T-cells via the CCR5 coreceptor. It is indicated for combination therapy in treatment-experienced adults infected with CCR5-tropic HIV-1 that is resistant to multiple antiretroviral agents. (2) Results from two randomized controlled trials (RCTs) indicate that in treatment experienced patients, maraviroc, combined with optimized background therapy (OBT), significantly decreases the level of HIV-1 RNA in the blood (viral load) when compared with OBT alone. The number of patients achieving undetectable viral loads and CD4+ cell count increases were also significantly higher in those receiving maraviroc. (3) Most patients experiencing treatment failure with maraviroc exhibit tropism changes from CCR5-tropic to CXCR4-using virus, but there is no evidence of disease progression. (4) Adverse effects reported with maraviroc include cough, fever, upper respiratory tract infections, rash, muscle and joint pain, abdominal pain, and postural hypotension (dizziness). No significant increases in cardiovascular events, hepatotoxicity, infections or malignancies have been reported with short-term maraviroc therapy. Several post-marketing studies will assess maraviroc's long-term safety for immune function, liver function, malignancy, cardiac events, and risks associated with changes in tropism. (5) Results from an ongoing trial in treatment naive patients suggest that maraviroc may not be superior in terms of viral suppression to standard therapy, but may significantly increase the number of CD4+ T-cells.

Virologic and immunologic impact and durability of enfuvirtide-based antiretroviral therapy in HIV-infected treatment-experienced patients in a clinical setting.

OBJECTIVE: To evaluate the effectiveness and safety of enfuvirtide-based therapy in treatment-experienced patients in a clinical setting. METHOD: Retrospective study of treatment-experienced patients receiving enfuvirtide-based therapy for a minimum of 2 months. Endpoints included virologic suppression, virologic rebound, immunologic response, and adverse events. RESULTS: Sixty-four patients were eligible for inclusion in the analysis. Median baseline viral load and CD4+ count were 4.7 log10 copies/mL (interquartile range [IQR], 4.0-5.2) and 150 cells/mm3 (IQR, 60-250), respectively. At month 12, viral load declined by a median of 2.53 log10 copies/mL (IQR, 0.97-3.12). The unadjusted median time to virologic suppression was 7.7 months (95% CI 4.1-10.4 months). Baseline viral load and number of protease inhibitors in the current regimen were significantly associated with virologic suppression following multivariate analysis (hazard ratio [HR] 0.45, 95% CI 0.31-0.63, p < .0001, and HR 0.51, 95% CI 0.27-0.94, p = .03, respectively). Among the 42 patients who attained sustained virologic suppression, 10 experienced virologic rebound during a median follow-up of 13.3 months (IQR, 7.0-19.1). Injection site reactions were reported in 33 (52%) patients, resulting in treatment discontinuation in nine patients. CONCLUSION: Enfuvirtide-based therapy provides durable antiretroviral activity for treatment-experienced patients in a clinical setting.