Abstract:
:Active pharmaceutical ingredients (APIs) are the molecular entities that exert the therapeutic effects of medicines. This article provides an overview of the major APIs that are entered into antiretroviral therapy (ART), outlines how APIs are manufactured, and examines the regulatory and cost frameworks of manufacturing ART APIs used in low- and middle-income countries (LMICs). Almost all APIs for ART are prepared by chemical synthesis. Roughly 15 APIs account for essentially all of the ARTs used in LMICs. Nearly all of the ART APIs purchased through the Global Fund for AIDS, TB and Malaria (GFATM) or the United States President's Emergency Plan for AIDS Relief (PEPFAR) are produced by generic companies. API costs are very important because they are the largest contribution to the overall cost of ART. Efficient API production requires substantial investment in chemical manufacturing technologies and the ready availability of raw materials and energy at competitive prices. Generic API production is practiced in only a limited number of countries; the API market for ART is dominated by Indian companies. The quality of these APIs is ensured by manufacturing under good manufacturing practice (GMP), including process validation, testing against previously established specifications and the demonstration of clinical bioequivalence. The investment and personnel costs of a quality management system for GMP contribute significantly to the cost of API production. Chinese companies are the major suppliers for many advanced intermediates in API production. Improved chemistry of manufacturing, economies of scale and optimization of procurement have enabled drastic cost reductions for many ART APIs. The available capacity for global production of quality-assured APIs is likely adequate to meet forecasted demand for 2015. The increased use of ART for paediatric treatment, for second-line and salvage therapy, and the introduction of new APIs and combinations are important factors for the future of treatment in LMICs. The introduction of new fixed-dose combinations for ART and use of new drug delivery technologies could plausibly provide robust, durable ART for all patients in need, at an overall cost that is only moderately higher than what is presently being spent.
journal_name
Antivir Therjournal_title
Antiviral therapyauthors
Fortunak JM,de Souza RO,Kulkarni AA,King CL,Ellison T,Miranda LSdoi
10.3851/IMP2897subject
Has Abstractpub_date
2014-01-01 00:00:00pages
15-29eissn
1359-6535issn
2040-2058journal_volume
19 Suppl 3pub_type
杂志文章abstract:BACKGROUND:Two distinct inhibitors of the HCV protease have been approved for the treatment of patients infected with HCV genotype-1. These drugs are highly efficient in suppressing HCV replication; however, their use is limited by the emergence of viral mutants resistant to them after a very short time of treatment. B...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2326
更新日期:2013-01-01 00:00:00
abstract::To our knowledge, there are no previously published cases of enteroviral infection complicated by pityriasis lichenoides et varioliformis acuta (PLEVA). A 30-year-old woman is reported with a severe form of PLEVA, preceded by hand, foot and mouth disease. Immunosuppressive treatment with cyclosporin A resulted in rapi...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3012
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Zidovudine (3'-azido-3'-deoxythymidine, AZT), administered to pregnant women alone or in combination with other antiretroviral drugs, greatly reduces the mother-to-child transmission of HIV-1. The potential genotoxicity of these molecules is underestimated and wide-ranging evaluation of its biological and cl...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Peripheral neuropathy (PN) in HIV-infected individuals is thought be due to a toxic effect on mitochondria induced by some nucleoside reverse transcriptase inhibitors (NRTI). METHODS:A time-to-event analysis was performed using data from the Delta trial to study the incidence of PN in HIV-infected individua...
journal_title:Antiviral therapy
pub_type: 杂志文章,随机对照试验
doi:
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:It remains unclear whether depression in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) during pegylated interferon-based therapy is associated with the virus, drug or ethnic background. We aimed to perform a prospective study to evaluate the clinical course of depression and its predictors in conse...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2441
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:With the advent of the protease inhibitors boceprevir and telaprevir a novel therapy approach for HCV genotype 1 infected subjects has become standard of care. Quantification of HCV viral load (VL) represents an important predictor of treatment response. METHODS:Two different real-time PCR platforms, the CO...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2723
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Cerebrospinal fluid (CSF) HIV RNA is commonly used as a marker of compartmental antiviral activity in HIV-positive patients. Undetectable CSF HIV RNA levels have been associated with low CSF neopterin levels and better neurocognitive performances. The aim of this study was to analyse the prevalence and predi...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3140
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:No data are available on the clinical presentation and virological pattern in the case of failure of interferon (IFN)-free regimens in patients with genotype-3h. In this paper authors identified the virological and clinical characteristics of patients with genotype-3h treated with suboptimal or not indicated...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3228
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Current stopping rules during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment rely on week 12 HCV RNA response, but earlier identification of non-responders offers clinical and economic advantages. AIMS AND METHODS:To evaluate, among 129 HCV-genotype-1-infected, treatment-naive patients receiving p...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract::We report the first two paediatric cases of sofosbuvir treatment during high-intensity myeloablative conditioning and engraftment phases of haematopoietic stem cell transplantation. These reports highlight the safety of sofosbuvir during all phases of transplantation and the lack of interaction between sofosbuvir and ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3332
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Regulatory T-cells (Treg) hamper immune responses elicited by cancer vaccines. Therefore, depletion of Treg is being used to improve the outcome of vaccinations. METHODS:We studied whether an alphavirus vector-based immunotherapeutic vaccine changes the number and/or activity of Treg and if Treg depletion i...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1751
更新日期:2011-01-01 00:00:00
abstract:OBJECTIVE:To assess the effect of interleukin (IL)-2 combined with highly active antiretroviral therapy (HAART) on HIV-1 pro-viral DNA quantification in HIV-1-infected patients with CD4<200/mm3. PATIENTS AND METHODS:Seventy patients with CD4<200 cells/mm3 and CV<1000 copies/ml were enrolled in a 6-month randomized con...
journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2003-06-01 00:00:00
abstract:BACKGROUND:Sexually transmitted acute hepatitis C among HIV-positive homosexual men has been noted as an emerging epidemic. METHODS:Forty-seven patients with mainly sexually acquired, acute hepatitis C were enrolled in this prospective, multicentre trial, and 36 of these patients were treated within the acute phase of...
journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:2006-01-01 00:00:00
abstract::Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B is difficult to treat and there is little long-term data for lamivudine treatment of severe acute exacerbation. We report a prospective, consecutive cohort of severe acute exacerbation of HBeAg-negative chronic hepatitis B patients treated by lamivudine betwee...
journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章
doi:
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor drug, could be a favourable drug for maintenance therapy in HIV-infected adolescents because it has few long-term side effects. However, data among adolescents switching from efavirenz (EFV) to RPV are limited. This study investigated the ph...
journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究
doi:10.3851/IMP3198
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVES:HLA-B*5701 strongly predicts abacavir hypersensitivity (HSR), but implementation of effective routine screening into clinical practice requires testing be practical and accurate. We tested the proficiency of HLA-B*5701 typing among laboratories using sequence-specific primer PCR. DESIGN AND METHODS:DNA pane...
journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究
doi:
更新日期:2007-01-01 00:00:00
abstract:OBJECTIVE:To assess the tolerability, virological, immunological and clinical effects of nevirapine in the setting of a compassionate use programme in pretreated HIV-infected individuals. DESIGN:Retrospective observational cohort-study in 13 HIV-outpatient clinics in The Netherlands. METHODS: MAIN OUTCOME MEASURES:p...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:Scaling-up antiretroviral therapy (ART) in resource-limited settings has raised concerns of emerging HIV drug resistance (DR) and its transmission to newly infected individuals. To assess the prevalence of transmitted drug resistance (TDR) in recently HIV-infected individuals, a WHO TDR threshold survey was ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2999
更新日期:2016-01-01 00:00:00
abstract::In order to study the inhibitory effect of various reverse transcriptase inhibitors (RTIs) on cell-free HIV, we adapted a recently described in vitro system, based on co-cultures of dendritic cells and resting CD4 T cells, modelling early target cells during sexual transmission. The compounds tested included the secon...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2005-01-01 00:00:00
abstract::The hepatitis C virus (HCV) NS3 protein contains a serine proteinase domain implicated in the maturation of the viral polyprotein. NS3 forms a stable heterodimer with NS4A, a viral membrane protein that acts as an activator of the NS3 proteinase. The three-dimensional structure of the NS3 proteinase complexed with an ...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:
更新日期:1998-01-01 00:00:00
abstract::Since the outbreak of coronavirus disease (COVID-19) that was discovered in 2019 in Wuhan, China, no standard therapy guideline has been set despite the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its high infectivity. The globally pandemic outbreak suggests that COVID-19 is highly inf...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3362
更新日期:2020-06-04 00:00:00
abstract::HCV-related liver disease is an important contributor to morbidity and mortality in the HIV-infected population. Successful treatment of HIV-HCV-coinfected patients is followed by favourable clinical outcomes. While the combination of pegylated interferon and ribavirin remains the mainstay in the treatment of non-1 HC...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP2601
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:We sought to determine whether markers of systemic inflammation are associated with the presence of moderate/severe obstructive sleep apnea (OSA) and whether this association differs based on HIV and HIV treatment status. METHODS:HIV-uninfected men (HIV-; n=60), HIV-infected men receiving HAART (HIV+/HAART;...
journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究
doi:10.3851/IMP2745
更新日期:2014-01-01 00:00:00
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journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2004-12-01 00:00:00
abstract:BACKGROUND:Acute exacerbation (AE) in chronic hepatitis B (CHB) is usually followed by a spontaneous decline in HBV DNA levels. The subsequent treatment is controversial. In this study, we evaluated the efficacy and safety of pegylated interferon-α2a (PEG-IFN-α2a) for such CHB patients. METHODS:A total of 74 hepatitis...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2832
更新日期:2015-01-01 00:00:00
abstract::Zidovudine treatment of human immunodeficiency virus (HIV) infection induces drug-resistant viral strains harbouring specific amino acid substitutions in the reverse transcriptase (RT). To investigate whether this phenomenon could be observed in the case of human T lymphotropic virus type I (HTLV-I) infection, we anal...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract:BACKGROUND:This study investigated survival in people living with HIV being followed-up from 5 and 10 years after antiretroviral therapy (ART) initiation in a multi-country Asian cohort. METHODS:We included patients in follow-up >5 years after ART initiation. Factors associated with mortality beyond 5 and 10 years on ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3358
更新日期:2020-01-01 00:00:00
abstract::Weighted genotypic resistance scores represent a step towards excellence in the interpretation of HIV type-1 (HIV-1) resistance to antiretroviral drugs. They can predict phenotypic resistance and clinical response better than any other unweighted score. With the addition of mutations associated with an increased respo...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1671
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Prevalence and factors associated with sexual dysfunction in HIV-positive women are poorly known. METHODS:This was a cross-sectional study in a cohort of HIV-infected women. Clinically stable women were invited to participate in a female sexual dysfunction (FSD) evaluation with Female Sexual Function Index ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:In haematopoietic stem cell transplant (HSCT) recipients, cytomegalovirus (CMV) infection contributes significantly to morbidity and mortality in both the early and late post-transplant period. Ganciclovir (GCV) is the treatment of choice for CMV, but requires intravenous administration, a fact that complica...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1858
更新日期:2011-01-01 00:00:00