Antiretroviral Supply Research Articles

Population-based monitoring of HIV drug resistance early warning indicators in Uganda: A nationally representative survey following revised WHO recommendations.

IntroductionWith the scale-up of antiretroviral therapy (ART) there is a need to monitor programme performance to maximize ART efficacy and to prevent emergence of HIV drug resistance (HIVDR). In keeping with the elements of the World Health Organisation (WHO) guidance we carried out a nationally representative assessment of early warning indicators (EWI) at 304 randomly selected ART service outlets in Uganda.MethodsRetrospective patient data was extracted for the six EWIs for HIVDR including; on-time antiretroviral (ARV) drug pick-up, patient retention on ART at 12 months, ART dispensing practices, ARV drug stock-outs, viral load suppression (VLS) and viral load (VL) testing completion. Point prevalence for each clinic and national aggregate prevalence with 95% confidence intervals (CI) for all clinics were estimated and facility performances were computed and association between EWIs and programmatic factors assessed using Fisher’s Exact Test.ResultsFacilities meeting the EWI targets: on-time pill pick-up was 9.5%, more facilities in the north met this target (p = 0.040). Retention on ART at 12 months was 24.1%, facilities in Kampala region (p<0.001) and Specialized ART clinics (p = 0.01) performed better in this indicator. Pharmacy stock-outs was 33.6%, with more facilities in Kampala (p<0.001), specialized ART clinics (p<0.001) and private-for-profit (p<0.001) meeting this target. Dispensing practices was met by 100% of the facilities. VLS was met by 49.2% and 50.8% of facilities met VL completion target with facilities in central region performing better (p<0.001). National prevalence for the EWIs was: on-time pill pick-up 63.3% (CI: 58.9–67.8); retention on ART at 12 months 69.9% (CI: 63.8–76.0); dispensing practices 100.0%; VLS 85.2% (CI: 81.8–88.5) and VL completion, 60.7% (CI: 56.9–64.6).ConclusionDispensing practices in all facilities were in line with the national guidelines however, there still remains a challenge to long-term ART programmatic success in monitoring patient response to treatment, and maintaining patients on ART without interruptions arising due to poor patient adherence and as a consequence of ARV supply interruption. It is therefore of high importance that the national ART program ensures intensified follow-up for patients, ensuring uninterrupted supply of ARV drugs and increasing VL monitoring at treatment centres, in order to improve patient outcomes and avert preventable HIVDR

Gestion Et Dispensation Des Medicaments Antiretroviraux A Brazzaville : Cas Du Centre De Traitement Ambulatoire (Cta) Et De La Pharmacie Du Centre Hospitalier Et Universitaire De Brazzaville (Chub)

In Congo, the distribution of generic drugs including ARVs (Antiretrovirals) is done through dispensing sites. This paper focuses on describing the management, delivery, and supply of ARVs at two sites in Brazzaville, and thus contributes to improving the management of HIVpositive patients. This is a cross-sectional, observational, descriptive, and analytical study of 3,473 patients registered at the Hospital and University Hospital Pharmacy (CHUB) and Ambulatory Treatment Center (CTA) during the period from 1st January to December 31, 2010. The data were collected using medical records, prescriptions, inventory sheets, purchase orders, delivery notes of the Congolaise of Essential Medicines Generic (COMEG), and informal interview with the heads of dispensing units. Of the 3473 patients registered, there were 1412 men (40.65%) and 2061 women (59.34%). A sex ratio of 0.68 at the pharmacy of CHUB 13427 boxes of ARVs was ordered unlike the CTA where this number was 30810 boxes of ARV. The COMEG delivered to the CTA 28,667 boxes of ARVs (93.04%) dispensing 18,994 boxes. Half of the ARVs dispensed were the triple combinations (56,48%). At the CHUB pharmacy, COMEG delivered 15,371 boxes of ARVs, of which 28.16% is also a triple therapy. The analysis of the system revealed a poor estimate of needs because the dispensing and management of these drugs does not conform to the active queue.

Stock-outs! Improvisations and processes of infrastructuring in Uganda’s HIV/Aids and malaria programmes

ABSTRACTThis paper examines the stock-outs of medicines and diagnostic devices in Uganda. Our aim is to trace and compare interruptions in the supply of antiretrovirals and Rapid Diagnostic Tests in order to provide an ethnographic account of the complex role that improvisations play within global health infrastructures. We will argue that the fragmented and mobile infrastructures of these key global health technologies require and necessitate improvisations by the different actors involved as well as on almost all levels of the Ugandan health-care system. The extent and abundance of improvisations in itself works to acquire infrastructural capacities, a process that we will call the infrastructuring of care and treatment. We will also show how this process of infrastructuring of care and treatment – here rendered visible through improvisations – produces new dilemmas and uncertainties. Our approach to infrastructure challenges technocratic overtones prevalent in current debates around the much-needed strengthening of health systems. Our study of stock-outs aims to show how the infrastructure of under-resourced health systems is maintained by a complex nexus of socio-material practices and improvisations.

Pharmaceutical Equivalence of Distributed Generic Antiretroviral (ARV) in Asian Settings: The Cross-Sectional Surveillance Study - PEDA Study.

ObjectivesEnsuring that medicines meet quality standards is mandatory for ensuring safety and efficacy. There have been occasional reports of substandard generic medicines, especially in resource-limiting settings where policies to control quality may be less rigorous. As HIV treatment in Thailand depends mostly on affordable generic antiretrovirals (ARV), we performed quality assurance testing of several generic ARV available from different sources in Thailand and a source from Vietnam.MethodsWe sampled Tenofovir 300mg, Efavirenz 600mg and Lopinavir/ritonavir 200/50mg from 10 primary hospitals randomly selected from those participating in the National AIDS Program, 2 non-government organization ARV clinics, and 3 private drug stores. Quality of ARV was analyzed by blinded investigators at the Faculty of Pharmaceutical Science, Chulalongkorn University. The analysis included an identification test for drug molecules, a chemical composition assay to quantitate the active ingredients, a uniformity of mass test and a dissolution test to assess in-vitro drug release. Comparisons were made against the standards described in the WHO international pharmacopeia.ResultsA total of 42 batches of ARV from 15 sources were sampled from January–March 2015. Among those generics, 23, 17, 1, and 1 were Thai-made, Indian-made, Vietnamese-made and Chinese-made, respectively. All sampled products, regardless of manufacturers or sources, met the International Pharmacopeia standards for composition assay, mass uniformity and dissolution. Although local regulations restrict ARV supply to hospitals and clinics, samples of ARV could be bought from private drug stores even without formal prescription.ConclusionSampled generic ARVs distributed within Thailand and 1 Vietnamese pharmacy showed consistent quality. However some products were illegally supplied without prescription, highlighting the importance of dispensing ARV for treatment or prevention in facilities where continuity along the HIV treatment and care cascade is available.

Pretreatment antiretroviral exposure from recreational use

The international community has overcome many obstacles in making HIV antiretroviral (ARV) medication available globally, but ARV resistance in treatment-naive individuals remains an implementation challenge. The subject of many recent reports,1-3 worries abound that pretreatment ARV resistance is related to treatment failure and that further increases in the rates of pretreatment ARV resistance might “jeopardise the global HIV response”.1,2 Largely attributed to transmitted resistance, pretreatment ARV exposure such as inadequate treatment outside of sanctioned care networks is believed to be a contributing factor.3 While investigating HIV-risk behaviour in South Africa,4 we learned of a preventable form of pretreatment ARV exposure that has gone largely unreported and may accelerate rates of pretreatment ARV resistance: the recreational use of ARVs referred to by our informants as “whoonga”. Whereas whoonga has received significant media attention since 2010, the first and only report in the medical literature documenting the recreational use of ARVs appeared years earlier from the United States. In discussions with HIV-infected individuals in Miami about prescription drug diversion, Inciardi and colleagues learned that some individuals abuse efavirenz for its “intoxicating” effects and use ritonavir to enhance the effects of illicit drugs such as methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA/ecstasy).5 Claims about the psychoactive effects of these ARVs are supported by scientific case reports.6,7 Similar ARV abuse patterns in South Africa have been reported in the social science literature and news media. Larkan and colleagues provide an account of individuals smoking efavirenz in Western Cape and summarise media reports that ARVs are combined with illicit drugs such as opiates, methamphetamine, and/or marijuana to make drug cocktails.8 Whoonga, believed to be one such cocktail, brought media attention to the problem of recreational ARV use in Kwazulu-Natal because of its addictive potential, its association with criminal activity, and the challenge it posed to ARV rollout.9 Even local experts who maintain that whoonga is heroin and does not contain ARVs acknowledge that a number of South African drug abusers use ARVs recreationally.10 Although essentially a substance abuse problem, the implications for HIV treatment are broad. For example, diversion of ARVs, in addition to impacting adherence, reduces ARV supply and limits access to treatment. Criminal behaviour related to diversion of ARVs endangers patients and healthcare providers while deterring others from seeking care. Finally, the recreational use of ARVs further stigmatises HIV-infected patients and their communities and may undermine donor willingness to fund ARV treatment.8 In addition to these impacts, when untreated HIV-infected individuals are exposed to ARVs recreationally, they are at risk for acquiring resistance.8 Mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as efavirenz are among the most common in individuals with pretreatment ARV resistance.1-3 Interestingly, serum concentrations of ARVs including efavirenz have been detected in some HIV-infected individuals with pretreatment ARV resistance who deny prior history of ARV treatment.3 To help explain some of these findings, researchers may wish to inquire specifically about recreational ARV use or use of drug cocktails when assessing pretreatment ARV exposure. Expanding pretreatment ARV resistance screening will help to minimize the risk that this form of pretreatment ARV exposure poses; however, a comprehensive strategy to investigate this problem also involves expanding substance abuse research. Existing substance abuse surveillance methods have not reported on the phenomenon,11,12 and they may need to be improved if we are to understand the extent of pretreatment ARV exposure from recreational ARV use. Systematic research is also needed to explore the chemical makeup of South African street drugs, the abuse liability of ARVs, and the bioavailability and likelihood of developing resistance when ARVs are smoked or otherwise administered inappropriately. Given the high prevalence and complex medical, psychosocial, and political context of HIV in southern Africa, it is important that treatment strategies adapt to emerging issues like recreational ARV use. We may decrease the recreational use of ARVs, decrease drug diversion, and improve adherence to HIV treatment if we avoid ARVs used recreationally when developing ARV treatment guidelines or distribute ARVs to patients in a way that minimizes the potential for misuse. The recreational use of ARVs also serves as a reminder that ARV treatment is not synonymous with HIV treatment and demonstrates the importance of access to effective community-based mental health and substance abuse services.

A lifeline to treatment: the role of Indian generic manufacturers in supplying antiretroviral medicines to developing countries.

BackgroundIndian manufacturers of generic antiretroviral (ARV) medicines facilitated the rapid scale up of HIV/AIDS treatment in developing countries though provision of low-priced, quality-assured medicines. The legal framework in India that facilitated such production, however, is changing with implementation of the World Trade Organization Agreement on Trade-Related Aspects of Intellectual Property Rights, and intellectual property measures being discussed in regional and bilateral free trade agreement negotiations. Reliable quantitative estimates of the Indian role in generic global ARV supply are needed to understand potential impacts of such measures on HIV/AIDS treatment in developing countries.MethodsWe utilized transactional data containing 17,646 donor-funded purchases of ARV tablets made by 115 low- and middle-income countries from 2003 to 2008 to measure market share, purchase trends and prices of Indian-produced generic ARVs compared with those of non-Indian generic and brand ARVs.ResultsIndian generic manufacturers dominate the ARV market, accounting for more than 80% of annual purchase volumes. Among paediatric ARV and adult nucleoside and non-nucleoside reverse transcriptase inhibitor markets, Indian-produced generics accounted for 91% and 89% of 2008 global purchase volumes, respectively. From 2003 to 2008, the number of Indian generic manufactures supplying ARVs increased from four to 10 while the number of Indian-manufactured generic products increased from 14 to 53. Ninety-six of 100 countries purchased Indian generic ARVs in 2008, including high HIV-burden sub-Saharan African countries. Indian-produced generic ARVs used in first-line regimens were consistently and considerably less expensive than non-Indian generic and innovator ARVs. Key ARVs newly recommended by the World Health Organization are three to four times more expensive than older regimens.ConclusionsIndian generic producers supply the majority of ARVs in developing countries. Future scale up using newly recommended ARVs will likely be hampered until Indian generic producers can provide the dramatic price reductions and improved formulations observed in the past. Rather than agreeing to inappropriate intellectual property obligations through free trade agreements, India and its trade partners - plus international organizations, donors, civil society and pharmaceutical manufacturers - should ensure that there is sufficient policy space for Indian pharmaceutical manufacturers to continue their central role in supplying developing countries with low-priced, quality-assured generic medicines.

Suministro de antirretrovirales en Argentina: Programa Nacional de Lucha contra los Retrovirus del Humano, SIDA y ETS

To evaluate the supply cycle of antiretroviral (ARV) drugs, overseen by the National Program to Combat Human Retroviruses, AIDS, and STDs, through its order fulfillment indicators, and to obtain input from supply chain stakeholders. A study was carried out from April-September 2005 in the pharmacies of two hospitals in Rosario, Argentina, involving both a quantitative analysis of indicators and secondary sources and a qualitative evaluation using semistructured interviews. The indicators reveal the impact that interruptions in ARV supply stream from the Program (central level) have and the overstocking that takes place at the pharmacies (local level) to manage the shortages. Changes in ARV treatment account for over 50% of the prescriptions. Fulfillments fall short of the reference value. The interviewees shared possible strategies for overcoming the communication gaps between levels, for building-up stock, for guaranteeing availability, and for shortening waiting times; reached informal agreements to deal with the lack of policies and the shortage of staff; acknowledged the challenges facing the jurisdictions (central, intermediate, and local/community); and recognized local efforts to improve management. These challenges could be the starting point for building teams to work on effectively decentralizing the entire supply chain and allowing the Program to fulfill its much-needed oversight role.

A ROBUST OUTPUT–FEEDBACK TREATMENT SCHEDULING FOR HIV-1

Abstract In this paper an anti–retroviral supply treatment scheduling for a dynamical model of the HIV-1 is proposed. This therapy design problem is approached from an equilibrium point stabilization perspective by viewing the drug treatment as a control law. The main feature of the proposed controller is threefold, namely: It exploits the natural properties, for stabilization purposes, of the HIV-1 model leading to a quite simple structure. It is an output–feedback scheme in the sense that for achieving the desired stability properties it is not required neither feedback nor estimation of the unmeasurable state. It is robust against both parametric and structural uncertainties. The usefulness of the presented control scheme is illustrated via numerical simulations.

Designing Equitable Antiretroviral Allocation Strategies in Resource-Constrained Countries

BackgroundRecently, a global commitment has been made to expand access to antiretrovirals (ARVs) in the developing world. However, in many resource-constrained countries the number of individuals infected with HIV in need of treatment will far exceed the supply of ARVs, and only a limited number of health-care facilities (HCFs) will be available for ARV distribution. Deciding how to allocate the limited supply of ARVs among HCFs will be extremely difficult. Resource allocation decisions can be made on the basis of many epidemiological, ethical, or preferential treatment priority criteria.Methods and FindingsHere we use operations research techniques, and we show how to determine the optimal strategy for allocating ARVs among HCFs in order to satisfy the equitable criterion that each individual infected with HIV has an equal chance of receiving ARVs. We present a novel spatial mathematical model that includes heterogeneity in treatment accessibility. We show how to use our theoretical framework, in conjunction with an equity objective function, to determine an optimal equitable allocation strategy (OEAS) for ARVs in resource-constrained regions. Our equity objective function enables us to apply the egalitarian principle of equity with respect to access to health care. We use data from the detailed ARV rollout plan designed by the government of South Africa to determine an OEAS for the province of KwaZulu–Natal. We determine the OEAS for KwaZulu–Natal, and we then compare this OEAS with two other ARV allocation strategies: (i) allocating ARVs only to Durban (the largest urban city in KwaZulu–Natal province) and (ii) allocating ARVs equally to all available HCFs. In addition, we compare the OEAS to the current allocation plan of the South African government (which is based upon allocating ARVs to 17 HCFs). We show that our OEAS significantly improves equity in treatment accessibility in comparison with these three ARV allocation strategies. We also quantify how the size of the catchment region surrounding each HCF, and the number of HCFs utilized for ARV distribution, alters the OEAS and the probability of achieving equity in treatment accessibility. We calculate that in order to achieve the greatest degree of treatment equity for individuals with HIV in KwaZulu–Natal, the ARVs should be allocated to 54 HCFs and each HCF should serve a catchment region of 40 to 60 km.ConclusionOur OEAS would substantially improve equality in treatment accessibility in comparison with other allocation strategies. Furthermore, our OEAS is extremely different from the currently planned strategy. We suggest that our novel methodology be used to design optimal ARV allocation strategies for resource-constrained countries.