A oferta pública de medicamentos para aids e o papel de Farmanguinhos / Public supply of AIDS drugs and the role of Farmanguinhos

Resumo Este artigo descreve e analisa a participação do Instituto de Tecnologia em Fármacos (Farmanguinhos) na produção local de medicamentos antirretrovirais no Brasil. São também apresentadas as mudanças no padrão de provimento, a situação das parcerias para o desenvolvimento produtivo e a posição dos produtores nacionais para esses medicamentos. As estratégias metodológicas foram revisão bibliográfica, análise de documentos oficiais e dados fornecidos por Farmanguinhos e pelo Departamento de Condições Crônicas e Infecções Sexualmente Transmissíveis do Ministério da Saúde, via Lei de Acesso à Informação. Este artigo mostra que o estabelecimento das parcerias abriu novas perspectivas para o desenvolvimento da política de oferta pública de antirretrovirais para as pessoas vivendo com HIV, por contribuir para a sustentabilidade das despesas financeiras do Ministério da Saúde com medicamentos. Farmanguinhos é o laboratório público que fornece mais quantidades e recebe os maiores valores provenientes do fornecimento desses produtos ao Ministério da Saúde. Embora os medicamentos importados preponderem largamente em quantidade e valores pagos pelo Ministério da Saúde, Farmanguinhos permanece sendo um provedor fundamental na produção local de antirretrovirais. Apesar dos problemas verificados nas Parcerias, os ganhos nas competências tecnológicas na produção de antirretrovirais podem ampliar o horizonte tecnológico e produtivo do laboratório.

Abstract This article describes and analyses the part played by the Instituto de Tecnologia em Fármacos (Farmanguinhos) in local production of antiretroviral medicines in Brazil, as well as changes in the pattern of supply, the status of related Production Development Partnerships and the position of Brazilian producers of these medicines. The methodological strategies used were literature review and analysis of official documents and data provided by Farmanguinhos and by the Ministry of Health's Department of Chronic Conditions and Sexually Transmitted Infections, via the Information Access Law. This article shows that, by contributing to the sustainability of Ministry of Health expenditure on medicines, these partnerships have opened new prospects for developing the policy of public supply of antiretrovirals for people living with HIV. Farmanguinhos is the public laboratory that supplies the largest quantities of these products to the Ministry of Health and receives the largest revenues from supplying them. Although the imported medicines supplied to the Ministry of Health account for much larger quantities and revenues, Farmanguinhos continues to be a fundamentally important supplier of locally produced antiretrovirals. Despite the problems found in establishing the partnerships, the gains in antiretroviral production technology competences can broaden the laboratory's technological and production horizons.

COVID-19 pandemic and antiretrovirals (ARV) availability in Nigeria: recommendations to prevent shortages.

HIV/AIDS is an infectious disease that has claimed the lives of millions of people worldwide. Currently, there is no vaccine that has been developed in a bid to fight this deadly infection, however, antiretrovirals (ARVs), which are drugs used in the treatment of HIV infection are routinely prescribed to infected persons. They act via several mechanisms of action to reduce the severity of infection and rate of infectivity of the virus by decreasing the viral load while increasing CD4 counts. COVID-19 pandemic has resulted in unprecedented events affecting almost all areas of humans' life including availability of medicines and other consumables. This paper analyses the availability of ARVs during COVID-19 era and offered recommendations to be adopted in order to prevent shortages.

Impact of COVID-19 on the global supply chain of antiretroviral drugs: a rapid survey of Indian manufacturers.

Most people living with HIV in low- and middle-income countries are treated with generic antiretroviral (ARV) drugs produced by manufacturers in India - the "pharmacy of the developing world". India's nationwide lockdown in March 2020 in response to the coronavirus disease 2019 (COVID-19) pandemic therefore prompted concerns about disruption to this essential supply. A preliminary assessment of ARV drug manufacturers in India in March 2020 indicated a range of concerns. This prompted a rapid questionnaire-based survey in May 2020 of eight manufacturers that account for most of India's ARV drug exports. The greatest challenges reported were in international shipping, including delays, increased lead times and rising costs. Contrary to expectations, lack of access to the active pharmaceutical ingredients (APIs) required for ARV drug manufacture was not a major hindrance, as manufacturers reported that their reliance on China for API supplies had reduced in recent years. However, their reliance on overseas markets for the raw materials required for local API synthesis was a major challenge. The findings from this survey have implications for addressing some of the immediate and medium-term concerns about the production and supply of generic ARV drugs. Long-term orders to support multi-month dispensing and buffer stocks need to be in place, together with computerized inventory management systems with real-time information from the lowest-level dispensation unit. Manufacturers and industry associations should have regular, formal interaction with the key ministries of the Government of India regarding these issues. Measures to improve the resilience of the generic ARV drug supply system are essential to minimize ongoing supply shocks resulting from the COVID-19 pandemic and to prepare for future emergencies.

[Access to the management of HIV infected children: Overview of the healthcare supply in Cameroon in 2014]. / Accès à la prise en charge de l'infection VIH pédiatrique ­ État des lieux de l'offre des soins au Cameroun en 2014.

BACKGROUND: In Cameroon in 2012, the proportion (15%) of children eligible for antiretroviral treatment (ART) was one of the lowest among the 21 Global Fund priority countries. The objective of this study was to carry out a situational analysis of the existing care offer for pediatric HIV in Cameroon. METHODS: A descriptive cross-sectional study was conducted over a 4-month period (April to August 2014) in 12 healthcare facilities in 7 regions of Cameroon selected by systematic sampling. The data were collected in a self-administered questionnaire filled out by the caregiving and administrative personnel included in the study. RESULTS: All in all, 142 persons in charge of pediatric HIV treatment were included in the study, of whom 115 were working at the operational level: 59 (51.2%) health personnel, 44 (38.3%) community agents and 12 (10.4%) department heads; the other 27 exercised responsibilities at the regional (19) and the local (8) levels. An overwhelming majority of the caregivers involved in pediatric VIH treatment were nurses, a factor necessitating the delegation of medical tasks institutionalized in Cameroon. Few standardized nationwide documents take into account these treatment modalities. Inadequate dissemination of the documents at all levels of the healthcare pyramid may justify the non-compliance with the care protocols that has been observed in the training programs dedicated to the subject. CONCLUSION: The updating and large-scale dissemination of standardized nationwide documents taking into account the specificities of HIV-infected children are required to improve implementation at the operational level of the Cameroonian healthcare system of the existing guidelines for pediatric HIV treatment.

[Quick community survey on the impact of COVID-19 outbreak for the healthcare of people living with HIV].

Objective: To collect the current status and healthcare needs of people living with HIV (PLHIV) in China during the COVID-19 outbreak to inform quick response from government and communities. Methods: During February 5(th) to 10(th), 2020, a national anonymous survey was conducted using an online questionnaire among PLHIV at least 18 years of age and had started antiretroviral treatment (ART) to collect the information on COVID-19 prevention, HIV-related health services and the needs on psychosocial support. Current status and needs of people living with HIV were analyzed in Hubei and other regions. Results: A total of 1 014 valid questionnaires were collected, with PLHIV respondents cross the country. The survey revealed that 93.79% of the respondents could obtain information regarding the prevention of COVID-19 from their communities or villages. Respondents were concerned with HIV-specific protective measures and personal protective equipment shortage. 32.64% of all respondents were not carrying sufficient antiretroviral medicines (ARVs) to meet the needs under traffic and travel restrictions, and some could face stock-outs in the coming month. In Hubei province where 53 respondents needed ARV refill, 64.15% reported difficulty accessing ARV due to the "blockage" . 28.93% respondents were in need of sociopsychological support, and 85.31% anticipated further improvement of the out-of-town ARV refill process from the government. Conclusion: PLHIV wants to know HIV-specific protective measures against COVID-19 outbreak. PLHIV who returned to their home-towns and affected by the lock-downs reported challenges with refills. We should undertake a more systematic study on impacts of the COVID-19 on PLHIV to develop preparedness capacity for future public health emergency.

Are health workers reduced to being drug dispensers of antiretroviral treatment? A randomized cross-sectional assessment of the quality of health care for HIV patients in northern Uganda.

High quality of care (QoC) for antiretroviral treatment (ART) is essential to prevent treatment failure. Uganda, as many sub-Saharan African countries, increased access to ART by decentralizing provision to districts. However, little is known whether this rapid scale-up maintained high-quality clinical services. We assess the quality of ART in the Acholi and Lango sub-regions of northern Uganda to identify whether the technical quality of critical ART sub-system needs improvement. We conducted a randomized cross-sectional survey among health facilities (HF) in Acholi (n = 11) and Lango (n = 10). Applying lot quality assurance sampling principles with a rapid health facility assessment tool, we assessed ART services vis-à-vis national treatment guidelines using 37 indicators. We interviewed health workers (n = 21) using structured questionnaires, directly observed clinical consultations (n = 126) and assessed HF infrastructure, human resources, medical supplies and patient records in each health facility (n = 21). The district QoC performance standard was 80% of HF had to comply with each guideline. Neither sub-region complied with treatment guidelines. No HF displayed adequate: patient monitoring, physical examination, training, supervision and regular monitoring of patients' immunology. The full range of first and second line antiretroviral (ARV) medication was not available in Acholi while Lango had sufficient stocks. Clinicians dispensed available ARVs without benefit of physical examination or immunological monitoring. Patients reported compliance with drug use (>80%). Patients' knowledge of preventing HIV/AIDS transmission concentrated on condom use; otherwise it was poor. The poor ART QoC in northern Uganda raises major questions about ART quality although ARVs were dispensed. Poor clinical care renders patients' reports of treatment compliance as insufficient evidence that it takes place. Further studies need to test patients' immunological status and QoC in more regions of Uganda and elsewhere in sub-Saharan Africa to identify topical and geographical areas which are priorities for improving HIV care.

Associations Between Practices and Behaviors at the Health Facility Level and Supply Chain Management for Antiretrovirals: Evidence from Cameroon, Namibia, and Swaziland.

BACKGROUND: While measuring, monitoring, and improving supply chain management (SCM) for antiretrovirals (ARVs) is understood at many levels of health systems, a gap remains in the identification and measurement of facility-level practices and behaviors that affect SCM. This study identifies practices and behaviors that are associated with SCM of ARVs at the hospital level and proposes new indicators for measurement. METHODS: We performed an in-depth literature review to identify facility-level practices and behaviors and existing indicators that are associated with SCM. We used the United States Agency for International Development's 2013 National Supply Chain Assessment Toolkit to define 7 supply chain function areas to frame the study. Qualitative, semistructured key informant and focus group interviews were conducted in hospitals with health professionals from Cameroon, Namibia, and Swaziland to understand facility-level practices and behaviors. RESULTS: Using the results from 54 key informant and focus group interviews from 12 hospitals, we identified 30 practices and behaviors that may affect ARV SCM at the facility level. The following practice areas were particularly associated with SCM: order verification, actions taken when ARV stock is received, changes in prescription and dispensing due to ARV stock-out, actions to ensure patient adherence, and communication with other affiliated facilities and higher-level SCM. We subsequently developed measurable indicators for future research. CONCLUSION: This study characterizes facility-level practices and behaviors that can affect ARV SCM. It also identifies gaps in their measurement. While this study uses ARVs as a tracer medicine to understand gaps in practices at the facility level, many of the findings are more broadly applicable to other medicines in an integrated setting. This study provides real-world evidence and the groundwork for further research to characterize the link between 30 facility-level practices and behaviors and ARV SCM at the facility and central levels.

Does the political will exist to bring quality-assured and affordable drugs to low- and middle-income countries?

BACKGROUND: Increased coverage with antiretroviral therapy for people living with HIV in low- and middle-income countries has increased their life expectancy associated with non-HIV comorbidities and the need for quality-assured and affordable non-communicable diseases drugs . Funders are leaving many middle-income countries that will have to pay and provide quality-assured and affordable HIV and non-HIV drugs, including for non-communicable diseases. OBJECTIVE: To estimate costs for originator and generic antiretroviral therapy as the number of people living with HIV are projected to increase between 2016 and 2026, and discuss country, regional and global factors associated with increased access to generic drugs. METHODS: Based on estimates of annual demand and prices, annual cost estimates were produced for generic and originator antiretroviral drug prices in low- and middle-income countries and projected for 2016-2026. RESULTS: Drug costs varied between US$1.5 billion and US$4.8 billion for generic drugs and US$ 8.2 billion and US$16.5 billion for originator drugs between 2016 and 2026. DISCUSSION: The global HIV response increased access to affordable generic drugs in low- and middle-income countries. Cheaper active pharmaceutical ingredients and market competition were responsible for reduced drug costs. The development and implementation of regulatory changes at country, regional and global levels, covering intellectual property rights and public health, and flexibilities in patent laws enabled prices to be reduced. These changes have not yet been applied in many low- and middle-income countries for HIV, nor for other infectious and non-communicable diseases, that lack the profile and political attention of HIV. Licensing backed up with Trade-Related Aspects of Intellectual Property Rights safeguards should become the norm to provide quality-assured and affordable drugs within competitive generic markets. CONCLUSION: Does the political will exist among policymakers and other stakeholders to develop and implement these country, regional and global frameworks for non-HIV drugs as they did for antiretroviral drugs?

Demand and Supply Motivations for Antiretroviral Drugs in Illicit Street Markets: The Case of Atlanta, Georgia.

We studied the motivations behind supply and demand of antiretroviral drugs (ARVs) in the illicit street markets of the metropolitan statistical area of Atlanta, Sandy Springs, and Roswell, Georgia. We found that these two market actions were largely interdependent: 39.53% of participants said that they sold their ARVs to pay for personal needs, and 20.93% said that they bought ARVs because they had previously sold them to pay for personal needs. The pattern that emerged suggests that illicit street markets have become mechanisms through which HIV patients cooperate to achieve competing goals: cover personal needs and keep up, however imperfectly, with their medication regime. We also found that HIV patients used illicit street markets because they faced institutional deficiencies, such as exclusion from the Ryan White/ADAP program, long waiting times to see a doctor, and prescription delays.

Implementing an Integrated Pharmaceutical Management Information System for Antiretrovirals and Other Medicines: Lessons From Namibia.

The success of the Namibian government's "treatment for all" approach to control and stop the country's HIV epidemic is dependent on an uninterrupted supply of antiretrovirals (ARVs) for people living with HIV. The public health system in Namibia, however, was constrained by an inefficient paper-based pharmaceutical information system resulting in unreliable and inaccessible data, contributing to persistent stock-outs of ARVs and other essential pharmaceuticals. This article describes the incremental implementation of an integrated pharmaceutical management information system to provide timely and reliable commodity and patient data for decision making in Namibia's national antiretroviral therapy (ART) program and the Ministry of Health and Social Services (MoHSS). The system has 4 interlinked information tools: (1) the Electronic Dispensing Tool (EDT) that manages the dispensing and inventory of antiretrovirals at service delivery points; (2) the EDT national database, which facilitates the flow, storage, and collation of ART data at the central level; (3) the Facility Electronic Stock Card used to manage pharmaceutical stocks and report inventory movement data to the national level; and (4) the Pharmaceutical Management Information Dashboard that integrates all 3 tools plus the warehouse management tool used by the central and regional medical stores into 1 dashboard that serves as a platform for the analysis and dissemination of pharmaceutical information throughout the health system. Implementing the pharmaceutical management information system was a prolonged and complicated process, with key challenges related to user acceptance and human resource constraints. The integrated pharmaceutical management information system enables Namibia to collect more than 90% of transactional commodity and patient dispensing data from more than 85% of all ART sites. Health managers use information from the system for medicine quantification decisions and to improve pharmaceutical service delivery. The MoHSS and its partners in the national ART program use the information for monitoring the World Health Organization early warning indicators for HIV drug resistance; ART defaulter tracing; and for planning, reporting, and research purposes. Namibia's pharmaceutical management information system demonstrates the feasibility and benefits of integrating related tools while maintaining their specialized functionality to address country-specific information and inventory management needs.

Local Sourcing and Supplier Development in Global Health: Analysis of the Supply Chain Management System's Local Procurement in 4 Countries.

From 2006 to 2014, Supply Chain Management System (SCMS), the global procurement and distribution project for the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), distributed over US$1.6 billion worth of antiretroviral drugs and other health commodities, with over US$263 million purchased from local vendors in 14 countries in sub-Saharan Africa. A simple framework was developed and 39 local suppliers from 4 countries were interviewed between 2013 and 2014 to understand how SCMS local sourcing impacted supplier development. SCMS local suppliers reported new contracts with other businesses (77%), new assets acquired (67%), increased access to capital from local lending institutions (75%), offering more products and services (92%), and ability to negotiate better prices from their principles (80%). Additionally, 70% (n=27) of the businesses hired between 1 and 30 new employees after receiving their first SCMS contract and 15% (n=6) hired between 30 and 100 new employees. This study offers preliminary guidance on how bilateral and multilateral agencies could design effective local sourcing programs to create sustainable local markets for selected pharmaceutical products, laboratory, and transport services.

Does integrating AIDS treatment with food assistance affect labor supply? Evidence from Zambia.

In low income settings, food assistance is increasingly becoming part of AIDS treatment and care programs with the aim of improving adherence to AIDS treatment, enhancing household food security and strengthening economic wellbeing. Yet, evidence of its economic impact is sparse. This paper uses primary data to examine the short term impact of a food assistance program on labor supply as measured by the hours worked, labor market participation rates and transitions to employment within HIV/AIDS affected households in Zambia. We find that food assistance is generally a labor supply disincentive to HIV-infected patients receiving treatment as it reduced their hours worked by up to 54%, transitions to employment by up to 70% and also reduced the labor market participation rates of male patients by 72%. Among non-infected adult family members, there were no significant effects on labor market participation. However, propensity score estimates show that food assistance generally increased the intensity of work by males regardless of the length of AIDS treatment, but for females there was a disincentive effect that disappeared when the patient had spent a longer time on AIDS treatment and was therefore healthier and less likely to be cared for. These findings suggest that food assistance can inadvertently reduce the labor supply of HIV-infected individuals, but this is compensated for by the increased labor supply among other family members.

The Effect of Antiretroviral Stock-Outs on Medication Adherence Among Patients Living With HIV in Ghana: A Qualitative Study.

Stock-outs of medications for antiretroviral therapy have been reported as a significant barrier to HIV care in sub-Saharan Africa, but patient responses to these shortages have not been fully described. The aim of our study was to employ qualitative methods to examine the role of medication stock-outs in contributing to treatment interruption among a sample of patients already engaged in care for HIV at Komfo Anokye Teaching Hospital in Kumasi, Ghana. We found that medication stock-outs presented a number of challenges to adherence for patients undergoing HIV treatment. Often, patients interrupted treatment until the stock-out ended. Those who did not interrupt treatment during stock-outs coped with shortages by stockpiling old medication or experienced clinic-initiated changes to their treatment regimens. Particularly in areas lacking the resources to monitor viral load or viral genotype, viral resistance could develop due to frequent unstructured treatment interruptions as a result of stock-outs.

From policy to practice: exploring the implementation of antiretroviral therapy access and retention policies between 2013 and 2016 in six sub-Saharan African countries.

BACKGROUND: Understanding the implementation of 2013 World Health Organization (WHO) consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection at the facility level provides important lessons for the roll-out of future HIV policies. METHODS: A national policy review was conducted in six sub-Saharan African countries to map the inclusion of the 2013 WHO HIV treatment recommendations. Twenty indicators of policy adoption were selected to measure ART access (n = 12) and retention (n = 8). Two sequential cross-sectional surveys were conducted in facilities between 2013/2015 (round 1) and 2015/2016 (round 2) from ten health and demographic surveillance sites in Kenya, Malawi, South Africa, Tanzania, Uganda and Zimbabwe. Using standardised questionnaires, facility managers were interviewed. Descriptive analyses were used to assess the change in the proportion of facilities that implemented these policy indicators between rounds. RESULTS: Although, expansion of ART access was explicitly stated in all countries' policies, most lacked policies that enhanced retention. Overall, 145 facilities were included in both rounds. The proportion of facilities that initiated ART at CD4 counts of 500 or less cells/µL increased between round 1 and 2 from 12 to 68%, and facilities initiating patients on 2013 WHO recommended ART regimen increased from 42 to 87%. There were no changes in the proportion of facilities reporting stock-outs of first-line ART in the past year (18 to 11%) nor in the provision of three-month supply of ART (43 to 38%). None of the facilities provided community-based ART delivery. CONCLUSION: The increase in ART initiation CD4 threshold in most countries, and substantial improvements made in the provision of WHO recommended first-line ART regimens demonstrates that rapid adoption of WHO recommendations is possible. However, improved logistics and resources and/or changes in policy are required to further minimise ART stock-outs and allow lay cadres to dispense ART in the community. Increased efforts are needed to offer longer durations between clinic visits, a strategy purported to improve retention. These changes will be important as countries move to implement the revised 2015 WHO guidelines to initiate all HIV positive people onto ART regardless of their immune status.

HIV antiretroviral medication stock-outs in Ghana: contributors and consequences.

Drug stock-outs are an unfortunate yet common reality for patients living in low and middle income countries, particularly in sub-Saharan Africa where trouble with consistent stock of antiretroviral medications (ARVs) continues. Our study takes a snapshot of this problem in Ghana. Although the country launched its antiretroviral therapy (ART) programme in 2003, progress toward realising the full benefit of ART for treated individuals has been limited, in part, because of stock-outs. In Ghana's Greater Accra region, we conducted semi-structured interviews with 40 women living with HIV (WLHIV) and 15 individuals with a history of HIV-related work in government or non-governmental organisations, or healthcare facilities. We used repeated review with coding and mapping techniques to analyse the transcripts and identify common themes. Stock-outs of ARVs result in inconsistent administration of therapy, increased indirect medical costs for WLHIV, and negative labelling of patients. Inefficiencies in drug supply, poor coordination with port authorities, inadequate government funding and dependence on international aid contribute to the stock-outs experienced in Ghana. Although using ARVs produced in-country could reduce supply problems, the domestically-manufactured product currently does not meet World Health Organization (WHO) standards. We recommend focused efforts to produce WHO standard ARVs in Ghana, and a review of current supply chain management to identify and mend pitfalls in the system.

Understanding how domestic health policy is integrated into foreign policy in South Africa: a case for accelerating access to antiretroviral medicines.

BACKGROUND: South Africa, as an emerging middle-income country, is becoming increasingly influential in global health diplomacy (GHD). However, little empirical research has been conducted to inform arguments for the integration of domestic health into foreign policy by state and non-state actors. This study seeks to address this knowledge gap. It takes the form of an empirical case study which analyses how South Africa integrates domestic health into its foreign policy, using the lens of access to antiretroviral (ARV) medicines. OBJECTIVE: To explore state and non-state actors' perceptions regarding how domestic health policy is integrated into foreign policy. The ultimate goal of this study was to achieve better insights into the health and foreign policy processes at the national level. METHODS: Employing qualitative approaches, we examined changes in the South African and global AIDS policy environment. Purposive sampling was used to select key informants, a sample of state and non-state actors who participated in in-depth interviews. Secondary data were collected through a systematic literature review of documents retrieved from five electronic databases, including review of key policy documents. Qualitative data were analysed for content. This content was coded, and the codes were collated into tentative categories and sub-categories using Atlas.ti v.7 software. RESULTS: The findings of this work illustrate the interplay among social, political, economic and institutional conditions in determining the success of this integration process. Our study shows that a series of national and external developments, stakeholders, and advocacy efforts and collaboration created these integrative processes. South Africa's domestic HIV/AIDS constituencies, in partnership with the global advocacy movement, catalysed the mobilization of support for universal access to ARV treatment nationally and globally, and the promotion of access to healthcare as a human right. CONCLUSIONS: Transnational networks may influence government's decision making by providing information and moving issues up the agenda.