Prepared for the Eastern Cape Department of Health by a research consortium comprising the Social Aspects of HIV/AIDS and Health Research Programme of the Human Sciences Research Council, and the University of Limpopo, Medunsa Campus Published by HSRC Press Private Bag X9182, Cape Town, 8000, South Africa www.hsrcpress.ac.za © 2005 Human Sciences Research Council First published 2005 All rights reserved No part of this book may be reprinted or reproduced or utilised in any form or by any electronic, mechanical, or other means, including photocopying and recording, or in any information storage or retrieval system, without permission in writing from the publishers ISBN 0-7969-2125-3 Copy editing by Samantha Damons Typeset by Simon van Gend Cover design by Neeran Naidoo Print management by comPress Distributed in Africa by Blue Weaver PO Box 30370, Tokai, Cape Town, 7966, South Africa Tel: +27 (0) 21 701 4477 Fax: +27 (0) 21 701 7302 email: orders@blueweaver.co.za www.oneworldbooks.com Distributed in Europe and the United Kingdom by Eurospan Distribution Services (EDS) Henrietta Street, Covent Garden, London, WC2E 8LU, United Kingdom Tel: +44 (0) 20 7240 0856 Fax: +44 (0) 20 7379 0609 email: orders@edspubs.co.uk www.eurospanonline.com Distributed in North America by Independent Publishers Group (IPG) Order Department, 814 North Franklin Street, Chicago, IL 60610, USA Call toll-free: (800) 888 4741 All other enquiries: +1 (312) 337 0747 Fax: +1 (312) 337 5985 email: frontdesk@ipgbook.com www.ipgbook.com CONTENTS List of tables and figures iv Foreword v Acknowledgements vi Abbreviations and acronyms vii Background Introduction The aim of this intervention study Rationale for designing the Nevirapine Unit Dose Pack Nevirapine dosing per National Protocol Preparation and distribution of mother and child Nevirapine Pack 10 Healthcare worker training The role of the pharmacist Results: healthcare workers' experiences and perceptions about the Nevirapine pack 13 10 Discussion 14 11 Recommendations 12 Conclusion Appendix 17 References 19 16 15 11 12 LIST OF TABLES AND FIGURES Tables Table 1.1: Access to healthcare facility for pregnant women in the Flagstaff district, Eastern Cape Table 1.2: Place where pregnant mothers delivered their last baby in the Flagstaff district, Eastern Cape Table 5.1: Nevirapine Protocol in the Eastern Cape (per National Protocol) Figures Figure 6.1: NVP pack label iv ©HSRC 2005 10 FOREWORD South Africa’s response to HIV and AIDS has evolved significantly over the last five years This has culminated in the implementation of programmes such as the Prevention of Mother-to-Child Transmission (PMTCT) that mitigate the impact of HIV to women and their children As a result, this has led to much excitement, innovation, achievements, opportunities and challenges for the Department of Health First, I would like to extend words of appreciation to the Human Sciences Research Council and the University of Limpopo (Medunsa campus) for the commitment and assistance in implementing the PMTCT programme in the Flagstaff (Qaukeni) area, and also acknowledge the efforts of the staff working in the rural health facilities in the same area Words of gratitude are also due to Dr Olive Shisana, Dr Henry Fomundam, Dr Thabang Mosala and Prof Karl Peltzer for leading this effort in assisting and supporting the rural women in Flagstaff to access single-dose Nevirapine for PMTCT I trust that the lessons learned from this study will be shared nationally and internationally by all concerned, and will improve services for HIV-infected pregnant women in rural and under-resourced communities Ms Nomalanga Makwedini Director HIV/AIDS & STIs Eastern Cape Department of Health v ©HSRC 2005 ACKNOWLEDGEMENTS The research consortium would like to thank the Ford Foundation for financial assistance and the healthcare workers (HCW) for making sure that this pilot project was successful Our special gratitude goes to the Department of Health in the Eastern Cape for providing the infrastructure: facilities, provision of Nevirapine, as well as the distribution and stock control of the Nevirapine pack vi ©HSRC 2005 ABBREVIATIONS AND ACRONYMS AIDS Acquired Immunodeficiency Syndrome ANC Antenatal clinics ARV Antiretrovirals AZT/ZDV Zidovudine FDA Food and Drug Administration HCW Healthcare workers HIVNET 012 HIV Network Prevention Study 012 HSRC Human Sciences Research Council HST Health Systems Trust MCC Medicines Control Council MTCT Mother-to-Child Transmission NIH National Institutes of Health NNRTI Non-nucleoside reverse transcriptase inhibitor NVP Nevirapine PACTG Paediatric AIDS Clinical Trials Group PMTCT Prevention of Mother-to-Child Transmission SAINT South African Intra-partum Nevirapine Trial TAC Treatment Action Campaign TBA Traditional birth attendant 3TC Lamivudine vii ©HSRC 2005 Background In 2001, the South African government developed a Nevirapine (NVP) protocol to be implemented in 18 selected pilot sites (two per province), for the Prevention of MotherTo-Child Transmission of HIV (PMTCT) programme The Medicines Control Council (MCC) had approved NVP for the reduction of vertical transmission of HIV from mother to child Zidovudine (AZT) protocol at that time had been approved by the Food and Drug Administration (FDA) and was being used by several developed countries This proved to be challenging, particularly for developing countries, because of the duration of treatment and infusion of the injectable form of AZT during labour and delivery In the Eastern Cape Province, two clinics were selected: the urban Cecilia Makiwane and the rural Umzimkhulu Clinics, as pilot sites to implement the PMTCT programme following the NVP protocol In the landmark case between the South African National Department of Health and the Treatment Action Campaign (TAC), the court ruled that the government should provide Nevirapine to HIV-positive pregnant mothers beyond the pilot sites The South African Cabinet then decided to extend the programme, to prevent transmission of HIV from mother to child in all health facilities that had an appropriate infrastructure The treatment was provided to all who needed it beyond the current experimental (pilot) sites It was therefore crucial for the Human Sciences Research Council (HSRC) to study the obstacles to effective implementation of this intervention and suggest ways of removing these barriers The HSRC has been conducting research in the area of PMTCT in three provinces: Western Cape, Eastern Cape and Gauteng The research began in January 2000, and some of its findings have been used to amend or modify the PMTCT approach in several clinical settings In the Eastern Cape the study was conducted in region E, Qaukeni District The communities in region E are rated among the most economically disadvantaged, with relatively poor access to services and less than 50 per cent having access to basic water supply and sanitation Many derive their household income from the migrant labour and pension grant systems, and there is a high rate of unemployment (48.5 per cent) The predominant housing type is a traditional mud-and-stick hut, with people living in dispersed homesteads It has a population density of 39 persons per square kilometre, far below that of Gauteng (385 per square kilometre) and KwaZulu-Natal (100 per square kilometre) The poverty rate (percentage of population in poverty) is 63.3 per cent, the second highest in the country The Human Development Index for the Eastern Cape was 0.51 in 1999 This is far lower than the rest of South Africa, with the exception of the Limpopo Province (Mahlalela, Rohde, Meidany, Hutchinson & Bennett 2001:3–5; RSA National Treasury 2001:2–3) In the study area, two hospitals, Holy Cross and St Elizabeth, render maternal health services They have five fixed clinics and a few mobile points 1.1 HIV prevalence in the Eastern Cape Province Data from the annual antenatal survey conducted by the Health Department, show high levels of infection among pregnant women attending antenatal clinics (ANC) in the Eastern Cape, and especially in region E where this study was being conducted The overall HIV prevalence among antenatal care attendees for the Eastern Cape, had risen from 21.5 per cent in 1998 to 22.0 per cent in 1999 and 24.0 per cent in 2000 to ©HSRC 2005 The Practicalities of Using Nevirapine for PMTCT in Under-resourced Settings 27.1 per cent in 2003 (Department of Health 2004) These figures are important for this study since they provide an indication of the number of women who need PMTCT services Region E has the highest levels of infection in the Eastern Cape, and the prevalence of HIV infection is increasing by more than one per cent annually In an HSRC baseline study in the Qaukeni district, data was collected on 534 pregnant women recruited at initial ANC visits in five PMTCT clinics (n=936), and 598 women from the community around the five clinics prior to ANC in the Flagstaff region (Peltzer et al., 2004) The study found the following: 1) Access to healthcare for pregnant women in most healthcare facilities was restricted by distance Only one in ten women was able to access hospital services within 30 minutes from where they lived Clinics were slightly more accessible than hospitals More than one in five women were able to access clinics services within 30 minutes from their homes However, two-thirds of the pregnant women took more than one hour to get to the nearest hospital, and almost one-third spent more than an hour getting to the nearest clinic (see Table 1.1) 2) Further evidence of lack of access to health services was that 42 per cent of those women who had delivered before (n=995) delivered at home (see Table 1.2), and that one in four women delivered at home without the services of a healthcare provider or a traditional birth attendant (TBA) Table 1.1: Access to healthcare facility for pregnant women in the Flagstaff district, Eastern Cape Time spent to get to nearest hospital Number of pregnant women Percentage 30 minutes and less 156 10.1 > 30 minutes to hour 370 24.1 > hour to hour 295 19.2 >2 hour 653 42.6 474 100.0 30 minutes and less 367 23.9 > 30 minutes to hour 624 40.7 > hour to hour 194 12.6 > hour 273 17.8 458 100.0 Total Time spent to get to nearest clinic Total Some of the findings of this study show that almost 60 per cent of the women deliver in the hospital, but it is of concern when more than 35 per cent of the women deliver at home, as shown in Table 1.2 The majority of the women live far away from the hospital, which is the only place where child delivery routinely takes place with a full PMTCT programme in place Most of the clinics not have delivery services ©HSRC 2005 Research questions regarding the interface of prevention of peri-natal HIV transmission, antiretroviral drug resistance, and antiretroviral treatment differ between resource-rich and resource-limited settings In resource-rich settings, a critical question is whether antiretroviral resistance among treatment-experienced pregnant women and increasing rates of resistance among antiretroviral-naive pregnant women, will result in higher rates of peri-natal transmission, reversing the currently successful peri-natal HIV prevention efforts In resource-limited settings, where antiretroviral therapy may become more available in the near future, critical questions revolve around whether widespread use of antiretrovirals such as NVP, ZDV, and Lamivudine (3TC) for PMTCT will lead to increased risk of treatment failure among women and infants who become infected despite prophylaxis, both of whom may later require antiretroviral drugs for their own healthcare The lack of data to address these questions has contributed to increased tension between treatment and peri-natal prevention advocates (Fowler et al., 2003) 2.1 NVP registration and use for PMTCT in South Africa The MCC is a statutory body that was established in terms of the Medicines and Related Substances Control Act 101 of 1965, to oversee the regulation of medicines in South Africa The MCC was appointed by the Minister of Health and its main purpose is to safeguard and protect the public through ensuring that all medicines that are sold and used in South Africa are safe, therapeutically effective and consistently meet acceptable standards of quality In April 2001, the MCC gave conditional approval status to the use of NVP as monotherapy for the reduction of MTCT of HIV The conditional status made it incumbent upon Boeringer-Ingelheim, the manufacturer of the product (the applicant), to monitor and report on safety, resistance and efficacy Nevirapine monotherapy was subsequently launched in 18 pilot sites in the country, two per province (one rural and one urban) In a case that was brought by the TAC against the government in April 2002 however, the Pretoria High Court ordered that the use of NVP monotherapy was to be expanded beyond the 18 pilot sites and be made available countrywide A clinical trial to determine the efficacy of oral AZT and oral NVP for prevention of vertical transmission of HIV-1 infection in pregnant Ugandan women and their neonates (HIVNET 012), was sponsored by NIH and conducted by investigators from Johns Hopkins University in the USA and Makerere University in Uganda The results provided the basis for MCC’s approval of NVP for that indication Prior to this study, the FDA and the MCC had already approved the use of NVP in combination with other ARVs for the treatment of HIV infection in adults and children The study was started in 1997 and completed in 1999, with the results, published in Lancet, concluding that NVP significantly reduced the risk of HIV transmission from mother to child Following the use of NVP in South Africa, there were concerns, discussions and debates by the MCC and scientists on the degree of its efficacy and the clinical significance of resistance This debate was aggravated by the withdrawal (by the applicant) of a NVP application to the FDA in March 2002, due to non-conformity with FDA regulatory requirements in the collection of primary data during the conduct of the study The MCC engaged the applicant and national and international scientists on the issue of efficacy and resistance in particular, for over a year In July 2004 the MCC concluded that ’the risk-benefit profile of NVP monotherapy has changed and therefore no longer recommends its use for prevention of MTCT of HIV’ It was further stated that ’council decision applies to all monotherapy interventions when used to reduce the risk of transmission of HIV from mother to child during labour Council is of the view that combination therapy should be considered for this indication’ ©HSRC 2005 The Practicalities of Using Nevirapine for PMTCT in Under-resourced Settings International organisations including the World Health Organisation had established the costs, feasibility and practicality of the AZT protocol in reducing vertical transmission of HIV from mother to child, and thus urged governments of developing countries to use NVP instead for this purpose NVP was recommended as a cost-effective, convenient intervention The Health Systems Trust (HST) published interim findings of lessons and recommendations from its study on the 18 national PMTCT pilot sites (McCoy, 2002) It concluded that many of the difficulties and constraints to full and effective implementation were identified as being systemic in nature, and related to the poor functioning of the healthcare system in general The report highlighted challenges regarding human resources, management and physical infrastructure They found tremendous differences in implementation and uptake rates between provinces and sites, and concluded that at the core of these differences were the large inequities in healthcare infrastructure within the country Other findings include the fact that up to as many as 15 per cent of pregnant women currently had access to PMTCT services; that 51 per cent of the pregnant women in the national pilot sites agreed to be tested; and that of those tested 30 per cent were HIVpositive Furthermore, less than one-third of the number of HIV-positive pregnant women identified in the national PMTCT sites had delivered with the administration of NVP to both mother and baby The HST study concluded that the provision of PMTCT could act as a catalyst for the improvement of the healthcare system ©HSRC 2005 The aim of this intervention study The overall purpose of this intervention was to focus on the implementation of the PMTCT protocol A particular area of concern was to ensure that pregnant women and their babies adhered to the NVP administration within the time frame of a dose to the mother during labour and a dose to the baby within 72 hours of birth Specific aims were to: • Design a user-friendly NVP (mother-infant pair) pack; • Evaluate the feasibility of dispensing the pack and successful administration of NVP using the pack; and • Evaluate acceptability by healthcare staff (nurses) and patients ©HSRC 2005 Rationale for designing the Nevirapine Unit Dose Pack In South Africa, the experience of dispensing and administering NVP has produced enormous challenges, especially in the rural areas These challenges relate particularly to patients living far from hospitals and clinics that have drug storage, dispensing and administration resources, as well as the problematic shortage of pharmacists and nurses to accurately dispense the required dose, and carry out monitoring The NVP suspension given to babies is currently only available in a 200ml bottle This makes accurate measuring and withdrawing of the very small dose of 0.6ml or the equivalent of 2mg per kg for each baby very challenging, as it would require approximately 333 withdrawals to finish the entire contents of the 200ml bottle This in turn, might also compromise aseptic techniques Pregnant women are normally supposed to be given a Nevirapine tablet at 28 weeks of gestation per protocol In some cases however, it is given during the first antenatal visit for fear that it may be the only visit prior to delivery Dispensing of NVP early as a single tablet increases the chances of the tablet being lost Due to distances from clinics or hospitals, and also the often hilly terrain, as well as other socio-economic factors, some women are forced to have their babies at home In such rural areas delivery of babies by TBAs is a long-standing tradition A significant number of these cases are unable to take their babies back to the delivery centre for the baby dose, which needs to be given within the stipulated 72 hours Furthermore, in some cases, for cultural reasons, babies can only be taken out of the house after a certain period (