An analysis of volumes, prices and pricing trends of the pediatric antiretroviral market in developing countries from 2004 to 2012.

Background: The pediatric antiretroviral (ARV) market is poorly described in the literature, resulting in gaps in understanding treatment access. We analyzed the pediatric ARV market from 2004 to 2012 and assessed pricing trends and associated factors.

Methods: Data on donor funded procurements of pediatric ARV formulations reported to the Global Price Reporting Mechanism database from 2004 to 2012 were analyzed.

Potential market size and impact of hepatitis C treatment in low- and middle-income countries.

The introduction of direct-acting antiviral agents (DAAs) has made hepatitis C infection curable in the vast majority of cases and the elimination of the infection possible. Although initially too costly for large-scale use, recent reductions in DAA prices in some low- and middle-income countries (LaMICs) has improved the prospect of many people having access to these drugs/medications in the future. This article assesses the pricing and financing conditions under which the uptake of DAAs can increase to the point where the elimination of the disease in LaMICs is feasible.

Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment: modelling study and economic analysis.

Background: With continued roll-out of antiretroviral therapy (ART) in resource-limited settings, evidence is emerging of increasing levels of transmitted drug-resistant HIV. We aimed to compare the effectiveness and cost-effectiveness of different potential public health responses to substantial levels of transmitted drug resistance.

Methods: We created a model of HIV transmission, progression, and the effects of ART, which accounted for resistance generation, transmission, and disappearance of resistance from majority virus in the absence of drug pressure.

Prices paid for adult and paediatric antiretroviral treatment by low- and middle-income countries in 2012: high, low or just right?

A viable market for antiretroviral drugs in low- and middle-income countries is key to the continued scale-up of antiretroviral treatment. We describe the price paid by low- and middle-income countries for 10 first- and 7 second-line adult and paediatric treatment regimens from 2003 to 2012, and compare the price of their finished formulations with the price of their active pharmaceutical ingredients in 2005, 2007, 2010 and 2012. Between 2003 and 2012 the median price of adult first-line treatment regimens per treatment-year decreased from USD499 to USD122, and that of second-line regimens from USD2,934 to USD497.

Systematic review of the use of dried blood spots for monitoring HIV viral load and for early infant diagnosis.

Background: Dried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID.

Methods And Findings: Thirteen peer reviewed HIV VL publications and five HIV EID papers were included.

The role of mathematical modelling in the development of recommendations in the 2013 WHO consolidated antiretroviral therapy guidelines.

Despite the exponential growth in the literature on modelling and simulation studies of impact and cost-effectiveness in different aspects of healthcare, there is no clear consensus on the appropriate role of modelling in the development of recommendations in clinical guidelines. This is compounded both by the lack of a standardised approach to assess the quality of modelling, and lack of clarity on its positioning within the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method for decision-making in the development of WHO guidelines, that considers both evidence from systematic reviews of randomized clinical trials (RTCs) or observational studies, together with stakeholder values and preferences, resource use, and feasibility issues. In the development of the 2013 WHO Consolidated Guidelines on the use of Antiretroviral drugs for treating and preventing HIV infection, a series of modelling projects were undertaken to inform the recommendations on eligibility criteria for ART initiation, and approaches to monitoring for treatment response.

Predicted levels of HIV drug resistance: potential impact of expanding diagnosis, retention, and eligibility criteria for antiretroviral therapy initiation.

Background: There is concern that the expansion of antiretroviral roll-out may impact future drug resistance levels and hence compromise the benefits of antiretroviral therapy (ART) at an individual and population level. We aimed to predict future drug resistance in South Africa and its long-term effects.

Methods: The previously validated HIV Synthesis model was calibrated to South Africa.

Update on World Health Organization HIV drug resistance prevention and assessment strategy: 2004-2011.

The HIV drug resistance (HIVDR) prevention and assessment strategy, developed by the World Health Organization (WHO) in partnership with HIVResNet, includes monitoring of HIVDR early warning indicators, surveys to assess acquired and transmitted HIVDR, and development of an accredited HIVDR genotyping laboratory network to support survey implementation in resource-limited settings. As of June 2011, 52 countries had implemented at least 1 element of the strategy, and 27 laboratories had been accredited. As access to antiretrovirals expands under the WHO/Joint United Nations Programme on HIV/AIDS Treatment 2.

Harnessing the prevention benefits of antiretroviral therapy to address HIV and tuberculosis.

After 30 years we are still struggling to address a devastating HIV pandemic in which over 25 million people have died. In 2010, an estimated 34 million people were living with HIV, around 70% of whom live in sub-Saharan Africa. Furthermore, in 2009 there were an estimated 1.

Investment in HIV/AIDS programs: does it help strengthen health systems in developing countries?

Background: There is increasing debate about whether the scaled-up investment in HIV/AIDS programs is strengthening or weakening the fragile health systems of many developing countries. This article examines and assesses the evidence and proposes ways forward.

Discussion: Considerably increased resources have been brought into countries for HIV/AIDS programs by major Global Health Initiatives.

Use of antiretroviral therapy in resource-limited countries in 2006: distribution and uptake of first- and second-line regimens.

Objective: To address the information gap on current use of antiretroviral drugs (ARTs) in developing countries.

Methods: The AIDS Medicines and Diagnostics Service of the World Health Organization (WHO) carried out a multi-country survey in early 2006. Questionnaires covered the use of first- and second-line regimens in adults and children, and the rates of switching from first-line to second-line regimen.

Examining the production costs of antiretroviral drugs.

Objectives: To present direct manufacturing costs and price calculations of individual antiretroviral drugs, enabling those responsible for their procurement to have a better understanding of the cost structure of their production, and to indicate the prices at which these antiretroviral drugs could be offered in developing country markets.

Methods: Direct manufacturing costs and factory prices for selected first and second-line antiretroviral drugs were calculated based on cost structure data from a state-owned company in Brazil. Prices for the active pharmaceutical ingredients (API) were taken from a recent survey by the World Health Organization (WHO).

The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings.

WHO has proposed a public-health approach to antiretroviral therapy (ART) to enable scaling-up access to treatment for HIV-positive people in developing countries, recognising that the western model of specialist physician management and advanced laboratory monitoring is not feasible in resource-poor settings. In this approach, standardised simplified treatment protocols and decentralised service delivery enable treatment to be delivered to large numbers of HIV-positive adults and children through the public and private sector. Simplified tools and approaches to clinical decision-making, centred on the "four Ss"--when to: start drug treatment; substitute for toxicity; switch after treatment failure; and stop--enable lower level health-care workers to deliver care.

The pricing and procurement of antiretroviral drugs: an observational study of data from the Global Fund.

The Purchase price report released in August 2004 by the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund) was the first publication of a significant amount of real transaction purchase data for antiretrovirals (ARVs). We did an observational study of the ARV transaction data in the Purchase price report to examine the procurement behaviour of principal recipients of Global Fund grants in developing countries. We found that, with a few exceptions for specific products (e.

What policymakers should know about drug resistance and adherence in the context of scaling-up treatment of HIV infection.

With the imminent massive scale up of antiretroviral therapy in developing countries concerns have been raised regarding the spectre of widespread viral drug resistance. These concerns should not lead to a slowing of the pace at which these life-preserving medications are made available to the millions in need in those countries. With proper HAART regimens and proper adherence, development of drug resistance is not a common event.

Factors associated with tuberculin skin test reactivity among HIV-infected people in Bangkok.

INH preventive therapy (IPT) has been shown in several randomized controlled trials to reduce the risk of developing active TB in tuberculin skin test (TST) or purified protein derivative (PPD) positive HIV infected individuals. Detection of latent tuberculosis by TST and determination of factors associated with the PPD positivity in HIV-infected persons are important for the targeting of chemoprophylaxis. Six hundred asymptomatic and early symptomatic HIV-infected subjects attending the AIDS Clinic of the Chulalongkorn University Hospital, Bangkok, Thailand were enrolled in two randomized clinical trials of chemoprophylaxis against TB from December 1994 to December 1996.

How human immunodeficiency virus voluntary testing can contribute to tuberculosis control.

Human immunodeficiency virus (HIV) is fueling the tuberculosis (TB) epidemic, particularly in sub-Saharan Africa. However, despite their close epidemiological links, the public health responses have largely been separate. WHO has set out a strategy to decrease the burden of HIV-related TB, comprising interventions against both TB and HIV.

Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial.

Background: Nonoxynol-9 (rINN, nonoxinol-9) is an over-the-counter spermicide that has in-vitro anti-HIV-1 activity. Results of studies of its effectiveness in prevention of HIV-1 infection in women have been inconclusive. We aimed to assess effectiveness of this vaginal gel.

Safety of multiple daily applications of COL-1492, a nonoxynol-9 vaginal gel, among female sex workers. COL-1492 Phase II Study Group.

Rationale: COL-1492 is a nonoxynol-9 (N-9)-containing vaginal gel and may be a potential microbicide. As part of an effectiveness trial, an initial toxicity study was conducted.

Objectives: The main objective of the reported study was the assessment of the toxicity of a 52.

A randomized, double-blind, placebo-controlled trial of single-dose ciprofloxacin versus erythromycin for the treatment of chancroid in Nairobi, Kenya.

A randomized, double-blind, placebo-controlled clinical trial was conducted in Nairobi, Kenya, to compare single-dose ciprofloxacin with a 7-day course of erythromycin for the treatment of chancroid. In all, 208 men and 37 women presenting with genital ulcers clinically compatible with chancroid were enrolled. Ulcer etiology was determined using culture techniques for chancroid, serology for syphilis, and a multiplex polymerase chain reaction for chancroid, syphilis, and herpes simplex virus (HSV).

Lack of efficacy of low dose oral interferon alfa in symptomatic HIV-1 infection: a randomised, double blind, placebo controlled trial.

Background: Interferon alfa (IFN-alpha) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-alpha concentrations > or = 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural human (nHu) IFN-alpha resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections without additional treatment. Moreover, loss of HIV antibody seropositivity was reported in approximately 10% of treated patients.