Determinants of HIV late presentation among men who have sex with men in Portugal (2014-2019): who's being left behind?

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.

Viral genetic clustering and transmission dynamics of the 2022 mpox outbreak in Portugal.

Pathogen genome sequencing during epidemics enhances our ability to identify and understand suspected clusters and investigate their relationships. Here, we combine genomic and epidemiological data of the 2022 mpox outbreak to better understand early viral spread, diversification and transmission dynamics. By sequencing 52% of the confirmed cases in Portugal, we identified the mpox virus sublineages with the highest impact on case numbers and fitted them into a global context, finding evidence that several international sublineages probably emerged or spread early in Portugal. We estimated a 62% infection reporting rate and that 1.3% of the population of men who have sex with men in Portugal were infected. We infer the critical role played by sexual networks and superspreader gatherings, such as sauna attendance, in the dissemination of mpox virus. Overall, our findings highlight genomic epidemiology as a tool for the real-time monitoring and control of mpox epidemics, and can guide future vaccine policy in a highly susceptible population.

A cross-sectional assessment of frailty, falls and perceptions of ageing in people living with HIV using an mHealth platform.

OBJECTIVE: To evaluate frailty, falls and perceptions of ageing among clinically stable individuals with HIV, engaged with remote healthcare delivered via a novel smartphone application. METHODS: This was a multi-centre European cross-sectional, questionnaire-based sub-study of EmERGE participants. Frailty was assessed using the five-item FRAIL scale. Present criteria were summed and categorized as follows: 0, robust; 1-2, pre-frail; 3-5, frail. Falls history and EQ-5D-5L quality of life measure were completed. Participants were asked their felt age and personal satisfaction with ageing. RESULTS: A total of 1373 participated, with a mean age of 45 (± 9.8) years. Frailty was uncommon at 2%; 12.4% fell in the previous year, 58.8% of these recurrently. Mood symptoms and pain were prevalent, at 43.3% and 31.8%, respectively. Ageing satisfaction was high at 76.4%, with 74.6% feeling younger than their chronological age; the mean felt age was 39.3 years. In multivariable analysis, mood symptoms and pain were positively associated with frailty, falls and ageing dissatisfaction. An increase in pain severity and mood symptoms were respectively associated with 34% and 63% increased odds of pre-frailty/frailty. An increment in pain symptoms was associated with a 71% increase in odds of falling. Pain was associated with ageing poorly, as were mood symptoms, with odds of dissatisfaction increasing by 34% per increment in severity. CONCLUSIONS: Although uncommon, frailty, falls and ageing dissatisfaction were seen in a younger cohort with medically stable HIV infection using a remote care model, promoting screening as advocated by European guidelines. These were more common in those with pain or mood symptoms, which should be proactively managed in clinical care and explored further in future research.

Efficiency of the EmERGE Pathway of Care in Five European HIV Centres.

OBJECTIVE: We aimed to calculate the efficiency of the EmERGE Pathway of Care in five European HIV clinics, developed and implemented for medically stable people living with HIV. METHODS: Participants were followed up for 1 year before and after implementation of EmERGE, between April 2016 and October 2019. Micro-costing studies were performed in the outpatient services of the clinics. Unit costs for outpatient services were calculated in national currencies and converted to US$ 2018 OECD purchasing parity prices to enable between clinic comparisons in terms of outcomes and costs. Unit costs were linked to the mean use of services for medically stable people living with HIV,  before and after implementation of EmERGE. Primary outcome measures were CD4 count and viral load; secondary outcomes were patient activation (PAM13) and quality of life (PROQOL-HIV). Out-of-pocket expenditure data were collected. RESULTS: There were 2251 participants: 87-93% were male, mean age at entry was 41-47 years. Medically stable people living with HIV had outpatient visits in four sites which decreased by 9-31% and costs by 5-33%; visits and costs increased by 8% in one site, which had to revert back to face-to-face visits. Antiretroviral drugs comprised 83-91% of annual costs: the Portuguese site had the highest antiretroviral drug costs in US$ purchasing parity prices. Primary and secondary outcome measures of participants did not change during the study. CONCLUSIONS: EmERGE is acceptable and provided cost savings in different socio-economic settings. Antiretroviral drug costs remain the main cost drivers in medically stable people living with HIV. While antiretroviral drug prices in local currencies did not differ that much between countries, conversion to US$ purchasing parity prices revealed antiretroviral drugs were more expensive in the least wealthy countries. This needs to be taken into consideration when countries negotiate drug prices with pharmaceutical vendors. Greater efficiencies can be anticipated by extending the use of the EmERGE Pathway to people with complex HIV infection or other chronic diseases. Extending such use should be systematically monitored, implementation should be evaluated and funding should be provided to monitor and evaluate future changes in service provision.

HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019.

Objective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.

The efficiency of the EmERGE platform for medically stable people living with HIV in Portugal.

Background: The aim of this study was to calculate the cost-effectiveness of the EmERGE Pathway of Care for medically stable people living with HIV in the Hospital Capuchos, Centro Hospitalar Universitário de Lisboa Central (HC-CHLC). The app enables individuals to receive HIV treatment information and communicate with caregivers. Methods: This before-and-after study collected the use of services data 1 year before implementation and after implementation of EmERGE from November 1, 2016, to October 30, 2019. Departmental unit costs were calculated and linked to mean use of outpatient services per patient-year (MPPY). Annual costs per patient-year were combined with primary (CD4 count; viral load) and secondary outcomes (PAM-13; PROQOL-HIV). Results: Five hundred eighty-six EmERGE participants used HIV outpatient services. Annual outpatient visits decreased by 35% from 3.1 MPPY (95% confidence interval [CI]: 3.0-3.3) to 2.0 (95% CI: 1.9-2.1) as did annual costs per patient-year from €301 (95% CI: €288-€316) to €193 (95% CI: €182-€204). Laboratory tests and costs increased by 2%, and radiology investigations decreased by 40% as did costs. Overall annual cost for HIV outpatient services decreased by 5% from €2093 (95% CI: €2071-€2112) to €1984 (95% CI: €1968-€2001); annual outpatient costs decreased from €12,069 (95% CI: €12,047-€12,088) to €11,960 (95% CI: €11,944-€11,977), with 83% of annual cost because of antiretroviral therapy (ART). Primary and secondary outcome measures did not differ substantially between periods. Conclusions: The EmERGE Pathway produced cost savings after implementation-extended to all people living with HIV additional savings are likely to be produced, which can be used to address other needs. Antiretroviral drugs (ARVs) were the main cost drivers and more expensive in Portugal compared with ARV costs in the other EmERGE sites.

"Moving Fourth": Introduction of a practical toolkit for shared decision-making to facilitate healthy living beyond HIV viral suppression.

An extension of the UNAIDS 90-90-90 target proposes >90% of people living with HIV (PLHIV) should have good health-related quality of life (HrQoL); however, limited guidance exists. The "Health Goals for Me" framework, an individualized approach to HIV care, provides a framework to assess HrQoL. We analyzed several patient-reported outcome measures (PROMs) to develop a practical toolkit to facilitate shared physician-patient decision-making. HrQoL subdomains, actionable in the clinical setting and measurable as PROMs, were selected. PROMs were collated through systematic literature searches, scored by the authors on usability, validation, and availability, after which practical recommendations were made. Nine subdomains were selected across physical, psychological, social, and environmental domains; 46 validated PROMs were identified. After pre-screening, from 39 evaluated PROMs, we recommended PROMs in the following subdomains: fatigue/energy loss, frailty/resilience, sleep disturbance, substance use, anxiety/depression, cognition, sexual function and desire, and stigma. Using this toolkit, healthcare professionals and PLHIV can collaborate and mutually agree on individual care objectives. Following the "Health Goals for Me" framework, appropriate care interventions can be implemented and reviewed in a continuous cycle. We discussed how eHealth interventions, which will have increasing importance in the post-COVID era, can facilitate improved HrQoL for PLHIV by utilizing toolkits such as the one described here. Implementation of this practical framework and the PROMs toolkit could provide a useful approach to assessing HrQoL in PLHIV and could enhance the physician's ability to gain valuable insights into the patient's daily life across a broad range of HrQoL issues.

Meglumine antimoniate combination treatment for relapsing Kala-azar after treatment and secondary prophylaxis failure with liposomal amphotericin B in two HIV-coinfected patients.

Visceral leishmaniasis (VL) is a protozoan infection caused by Leishmania infantum and L. donovani with a higher incidence and severity in HIV-infected patients due to its synergistic effect on hampering the immune response, often leading to death after treatment failure. Literature regarding the management of relapsing VL in HIV-coinfected patients is lacking. Many experts recommend a combined therapy with liposomal amphotericin B and miltefosine. The use of pentavalent antimonials is often discouraged due to their toxicity. We report two cases of successful response to treatment with combined therapy with meglumine antimoniate followed by secondary prophylaxis with miltefosine and atovaquone on relapsing VL in two HIV-coinfected patients despite treatment and monthly prophylaxis with appropriate doses of liposomal amphotericin B.

"Moving Fourth": A Vision Toward Achieving Healthy Living with HIV Beyond Viral Suppression.

Since HIV has evolved from being a fatal illness to a chronic condition, this brings new challenges relating to long-term health, as increasing numbers of people living with HIV (PLHIV) navigate their lives beyond viral suppression. This review presents the challenges facing patients and health-care providers managing HIV in Europe today. We highlight the challenges that the evolving landscape in HIV brings, including managing an aging and more diverse population of PLHIV; this requires a shift from managing disease to managing health and may best be achieved by multidisciplinary teams in the long term. We introduce the concept of "health goals for me:" an individualized approach to the management of HIV, and use this as the basis for a proposed framework for assessing health-related quality of life for PLHIV. Our framework comprises a continuous cycle of "ask and measure," "feedback and discussion," and "intervention," based on collaboration between the health-care professional and patient. For improved long-term management of PLHIV, we consider that this framework should become an intrinsic part of HIV care in the future and that the "health goals for me" concept be used as a tool to facilitate healthy living for PLHIV beyond viral suppression.

Long-Term Efficacy, Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naïve Patients with HIV-1 Infection: the REMAIN Study.

BACKGROUND: Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited. OBJECTIVE: We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study. METHODS: This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naïve patients aged ≥ 18 years initiating a first-line ATV/r-containing regimen. RESULTS: Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA < 50 copies/mL) was 0.79 (95% CI: 0.75, 0.83) at five years. No treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years. CONCLUSIONS: In a real-life clinical setting over five years, treatment-naïve patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long-term safety profile consistent with that observed in clinical trials, and no significant decline in renal function.

HIV-Associated Facial Lipodystrophy: Experience of a Tertiary Referral Center With Fat and Dermis-Fat Compound Graft Transfer.

Objectives: HIV-associated lipodystrophy is a common comorbidity in HIV-infected patients, having a profound impact on every aspect of patients' lives, particularly when involving the face. Hence, it is of the utmost importance to evaluate the result of any potential therapies that may help solve HIV-associated facial lipodystrophy. The aim of this article was to evaluate the outcome of patients undergoing facial lipodystrophy correction surgery within our institution. Methods: A retrospective analysis of the clinical charts and iconographic information of patients regarding demographics, morphologic changes, surgical option, postoperative complications, results, and patient satisfaction assessed by a 1- to 10-point scale and by the Assessment of Body Change and Distress questionnaire. Results: Twenty-three patients were operated on from March 2011 to April 2015. Seventy-five percent of cases were treated with fat graft injection, whereas dermis-fat grafts were applied in 25% of patients. The former had their fat harvested more commonly from the abdomen, whereas in the latter case, the graft was harvested mostly from the inner aspect of arms. The mean volume of fat injected on each side of the face was 28.5 ± 22.7 mL. On a scale from 1 to 10, mean patient satisfaction was 7.7 ± 2.8. The Assessment of Body Change and Distress questionnaire revealed statistically significant improvements. Complications occurred in 25% of cases, the most frequent being significant reabsorption. No major complications occurred. Conclusions: Treatment of HIV-associated facial lipodystrophy with autologous fat or dermis-fat compound graft is a safe procedure with long-lasting results and unquestionable aesthetic and social benefits.

Direct treatment costs of HIV/AIDS in Portugal / Custos diretos com tratamento do VIH/SIDA em Portugal / Costos originados por tratamiento del VIH/SIDA en Portugal

OBJECTIVE To analyze the direct medical costs of HIV/AIDS in Portugal from the perspective of the National Health Service. METHODS A retrospective analysis of medical records was conducted for 150 patients from five specialized centers in Portugal in 2008. Data on utilization of medical resources during 12 months and patients’ characteristics were collected. A unit cost was applied to each care component using official sources and accounting data from National Health Service hospitals. RESULTS The average cost of treatment was 14,277 €/patient/year. The main cost-driver was antiretroviral treatment (€ 9,598), followed by hospitalization costs (€ 1,323). Treatment costs increased with the severity of disease from € 11,901 (> 500 CD4 cells/µl) to € 23,351 (CD4 count ≤ 50 cells/ µl). Cost progression was mainly due to the increase in hospitalization costs, while antiretroviral treatment costs remained stable over disease stages. CONCLUSIONS The high burden related to antiretroviral treatment is counterbalanced by relatively low hospitalization costs, which, however, increase with severity of disease. The relatively modest progression of total costs highlights that alternative public health strategies that do not affect transmission of disease may only have a limited impact on expenditure, since treatment costs are largely dominated by constant antiretroviral treatment costs. .

OBJETIVO Analizar los costos médicos originados por tratamiento de VIH/SIDA, de acuerdo con la perspectiva del Servicio Nacional de Salud, en Portugal. MÉTODOS Se realizó análisis retrospectivo de registros médicos en muestra de 150 pacientes de cinco centros especializados, en 2008. Se obtuvieron datos de utilización de recursos médicos y de las características de los pacientes, en horizonte temporal de 12 meses. Se aplicó el costo unitario a cada componente de costo, usando fuentes oficiales y datos de contabilidad de los hospitales. RESULTADOS El costo promedio anual del tratamiento fue de 14,277€ por paciente. La parcela de costo más importante fue el relacionado con el tratamiento antiretrovial (9,598€), seguido por los costos de internación (1,323€). Los costos de tratamiento con severidad aumentaron de 11,901€ (> 500 CD4 células/µl) para 23,351€ (CD4 ≤ 50 células/µl). La progresión de los costos se debe mayormente al aumento de los costos de internación, dado que los costos por tratamiento antiretrovial se mantienen constantes a lo largo de las fases. CONCLUSIONES El elevado costo del tratamiento antiretrovial es compensado por el costo relativamente bajo de la internación, a pesar de que éste aumenta con la severidad. La baja progresión de los costos totales revela que estrategias de salud pública alternativas que no alteren la transmisión de la enfermedad tendrán sólo impacto limitado en los gastos, dado que los costos son mayormente influenciados por el tratamiento antiretrovial. .

OBJETIVO Analisar dos custos diretos médicos com VIH/SIDA, de acordo com a perspetiva do Serviço Nacional de Saúde, em Portugal. MÉTODOS Efetuou-se análise retrospectiva de registros médicos em amostra de 150 pacientes de cinco centros especializados em 2008. Foram obtidos dados de utilização de recursos médicos durante 12 meses e das características dos pacientes nesse período. Aplicou-se o custo unitário a cada componente de custo, usando fontes oficiais e dados contabilísticos dos hospitais. RESULTADOS O custo médio anual de tratamento foi de 14.277 euros por paciente. A parcela de custo mais importante foi o custo com o tratamento antirretroviral (9.598 euros), seguido dos custos de internação (1.323 euros). Os custos de tratamento com severidade aumentaram de 11.901 euros (> 500 CD4 células/µl) para 23.351 euros (CD4 ≤ 50 células/µl). A progressão dos custos deve-se principalmente ao aumento dos custos de internação, dado que os custos com tratamento antirretroviral se mantêm constantes ao longo dos estádios. CONCLUSÕES O custo elevado do tratamento antirretroviral é compensado com o custo relativamente baixo da internação, apesar deste aumentar com a severidade. A baixa progressão dos custos totais revela que estratégias de saúde pública alternativas que não alterem a transmissão da doença terão apenas impacto limitado nas despesas, dado que os custos são largamente influenciados pelo do tratamento antirretroviral. .

Direct treatment costs of HIV/AIDS in Portugal.

OBJECTIVE: To analyze the direct medical costs of HIV/AIDS in Portugal from the perspective of the National Health Service. METHODS: A retrospective analysis of medical records was conducted for 150 patients from five specialized centers in Portugal in 2008. Data on utilization of medical resources during 12 months and patients' characteristics were collected. A unit cost was applied to each care component using official sources and accounting data from National Health Service hospitals. RESULTS: The average cost of treatment was 14,277 €/patient/year. The main cost-driver was antiretroviral treatment (€ 9,598), followed by hospitalization costs (€ 1,323). Treatment costs increased with the severity of disease from € 11,901 (> 500 CD4 cells/µl) to € 23,351 (CD4 count ≤ 50 cells/ µl). Cost progression was mainly due to the increase in hospitalization costs, while antiretroviral treatment costs remained stable over disease stages. CONCLUSIONS: The high burden related to antiretroviral treatment is counterbalanced by relatively low hospitalization costs, which, however, increase with severity of disease. The relatively modest progression of total costs highlights that alternative public health strategies that do not affect transmission of disease may only have a limited impact on expenditure, since treatment costs are largely dominated by constant antiretroviral treatment costs.

The demise of multidrug-resistant HIV-1: the national time trend in Portugal.

OBJECTIVES: Despite a decreasing mortality and morbidity in treated HIV-1 patients, highly active antiretroviral treatment (HAART) can still fail due to the development of drug resistance. Especially, multidrug-resistant viruses pose a threat to efficient therapy. We studied the changing prevalence of multidrug resistance (MDR) over time in a cohort of HIV-1-infected patients in Portugal. PATIENTS AND METHODS: We used data of 8065 HIV-1-infected patients followed from July 2001 up to April 2012 in 22 hospitals located in Portugal. MDR at a specific date of sampling was defined as no more than one fully active drug (excluding integrase and entry inhibitors) at that time authorized by the Portuguese National Authority of Medicines and Health Products (INFARMED), as interpreted with the Rega algorithm version 8.0.2. A generalized linear mixed model was used to study the time trend of the prevalence of MDR. RESULTS: We observed a statistically significant decrease in the prevalence of MDR over the last decade, from 6.9% (95% CI: 5.7-8.4) in 2001-03, 6.0% (95% CI: 4.9-7.2) in 2003-05, 3.7% (95% CI: 2.8-4.8) in 2005-07 and 1.6% (95% CI: 1.1-2.2) in 2007-09 down to 0.6% (95% CI: 0.3-0.9) in 2009-12 [OR=0.80 (95% CI: 0.75-0.86); P<0.001]. In July 2011 the last new case of MDR was seen. CONCLUSIONS: The prevalence of multidrug-resistant HIV-1 is decreasing over time in Portugal, reflecting the increasing efficiency of HAART and the availability of new drugs. Therefore, in designing a new drug, safety and practical aspects, e.g. less toxicity and ease of use, may need more attention than focusing mainly on efficacy against resistant strains.

Antiretroviral therapy in treatment-naïve patients with HIV infection.

PURPOSE OF REVIEW: This review discusses the current status of antiretroviral therapy (ART) in treatment-naïve patients. ART initiation in such patients needs to be carefully planned, as the aim of therapy has shifted from prolonging life to ensuring maintained adherence to ART and optimization of quality of life. There is a plethora of first-line antiretroviral agents available, and physicians must consider several patient-related and therapy-related factors before selecting the most appropriate initial ART. RECENT FINDINGS: Current treatment guidelines recommend the use of nonnucleoside reverse transcriptase inhibitor (NNRTI), ritonavir-boosted protease inhibitor (PI), or integrase strand transfer inhibitor (INSTI)-based regimens in treatment-naïve patients. Treatment selection and modification to achieve optimal response is based primarily on regular assessment of viral load (and resistance testing if necessary) and CD4 cell count. The use of genotypic resistance testing, on initiation of therapy and on treatment failure, is becoming more widespread. In selected patients, due to increasing transmitted drug resistance (TDR), a PI-based regimen may be a better option. Classic ART combinations are being challenged by new combinations, although there is currently insufficient evidence to recommend use of the newer over classic combinations. Co-formulations of drugs and single-tablet regimens are fast becoming available and their convenience may increase patient treatment adherence. SUMMARY: All drug classes currently available for first-line ART are efficacious and have good tolerability; however, differences between individual drugs must be carefully considered when deciding a first-line regimen. Each first-line regimen must be tailored to the individual patient to attain optimal efficacy, acceptable long-term tolerability, and good adherence to ART.

Epithelioid Angiosarcoma in a Patient with Klippel-Trénaunay-Weber Syndrome: An Unexpected Response to Therapy.

We present a rare case of Stewart-Treves syndrome characterized by a diffuse angiosarcoma of the leg in a 22-year-old man with a history of chronic lymphedema due to Klippel-Trénaunay-Weber syndrome. He underwent limb disarticulation and medical treatment with cycles of doxorubicin, oral thalidomide and sunitinib with a very good response after 12 months of follow-up.

Abacavir versus zidovudine combined with lamivudine and efavirenz, for the treatment of antiretroviral-naive HIV-infected adults.

BACKGROUND: Zidovudine, lamivudine, and efavirenz comprise a highly effective and well-tolerated triple regimen for antiretroviral-naive patients. Evaluating other unique nucleoside reverse-transcriptase inhibitor (NRTI) combinations for long-term viral suppression is desirable. METHODS: This multicenter, randomized, double-blind noninferiority clinical trial compared the efficacy and safety of abacavir with that of zidovudine plus lamivudine and efavirenz in 649 antiretroviral-naive HIV-infected patients. The primary objective was a comparison of proportions of patients achieving plasma HIV-1 RNA levels

A 42-week open-label study to assess the pharmacokinetics, antiretroviral activity, and safety of amprenavir or amprenavir plus ritonavir in combination with abacavir and lamivudine for treatment of HIV-infected patients.

The pharmacokinetics, antiviral activity, and safety of an amprenavir-ritonavir (APV-RTV) 600/100 mg b.i.d. regimen and an APV-RTV 1200/200 mg q.d. regimen were studied in a human immunodeficiency virus (HIV)-infected population. The geometric least-square mean ratio (90% confidence interval) of steady-state trough concentrations, compared with that of the amprenavir 1200 mg b.i.d. regimen, was 6.08 (4.94-7.49) for the twice-daily APV-RTV regimen, and it was 4.19 (2.90-6.08) for the daily APV-RTV regimen. The regimens were well tolerated, which supports APV-RTV as an option for twice-daily or daily therapy for HIV.

Six-week randomized controlled trial to compare the tolerabilities, pharmacokinetics, and antiviral activities of GW433908 and amprenavir in human immunodeficiency virus type 1-infected patients.

This study compared the plasma amprenavir pharmacokinetics of the human immunodeficiency virus (HIV) protease inhibitors amprenavir (Agenerase) 1,200 mg twice daily (BID) and the amprenavir prodrug GW433908, a formulation that substantially reduces the number of tablets per dose compared with amprenavir, at doses of 1,395 mg and 1,860 mg BID, in combination with abacavir 300 mg BID and lamivudine 150 mg BID in patients with HIV infection. Overall, 78 patients received study treatment. Compared with amprenavir 1,200 mg BID, both GW433908 1,395 mg BID and GW433908 1,860 mg BID delivered equivalent steady-state (ss) values for area under the plasma amprenavir concentration-time curve (AUC) at the end of a dosing interval (tau), lower maximum plasma amprenavir concentrations (30% lower), and higher plasma amprenavir concentrations at the end of a dosing interval (28% higher for GW433908 1,395 mg BID and 46% higher for GW433908 1,860 mg BID). Time-variant plasma amprenavir pharmacokinetics were observed with reductions in plasma amprenavir exposure over the first 4 weeks of dosing; the decrease in plasma amprenavir AUC(tau,ss) versus the AUC from 0 h to infinity was 27% for GW43308 1,395 mg, 45% for GW433908 1,860 mg, and 23% for amprenavir 1,200 mg. All three regimens reduced plasma HIV-1 RNA ( approximately 2 log(10) copies/ml) and increased CD4(+) cell counts ( approximately 100 cells/mm(3)) over the initial 28 days. Adverse event profiles were consistent with those previously reported for amprenavir. Although not statistically tested, the GW433908 groups appeared to have fewer gastrointestinal symptoms. In conclusion, the protease inhibitor GW433908 delivered comparable plasma amprenavir concentrations to those delivered by amprenavir 1,200 mg BID. GW433908, in combination with abacavir and lamivudine, demonstrated potent antiviral activity and was generally well tolerated over a 4-week period.