SITUATION OF ANITRETROVIRAL DRUG USE IN NIGERIA FMOH IN COLLABORATION WITH WHO NOVEMBER 2003

Transcription

1 SITUATION OF ANITRETROVIRAL DRUG USE IN NIGERIA by FMOH IN COLLABORATION WITH WHO NOVEMBER

2 ACKNOWLEDGEMENTS... 3 GLOSSARY... 4 EXECUTIVE SUMMARY... 5 COUNTRY BAKGROUND... 8 Nigeria : demographic information... 8 HIV/AIDS in Nigeria... 8 ART program in Nigeria... 9 INTRODUCTION TO THE STUDY Study Objective...11 METHODOLOGY Structural and Process Indicators Drug Management and Rational Use of Drugs Access Rational Use Quality Scope and Limitations RESULTS National Level Structures and Processes Regulatory status of ARVs in Nigeria Essential Medicine List ARV supply system ARV financing Access to ARVs...15 Rational use of ARVs Intellectual property rights Facility Level Structures and Processes Personnel Patients Treatment and testing Methods of payment Monitoring and reporting Outcomes Access Affordability of the Triple Combination (Stavudine, Lamivudine and Nevirapine) Affordability of laboratory services Rational Use of ARVs Quality DISCUSSIONS National Structures and processes Facility structures and processes Access and quality Rational use of drugs RECOMMENDATIONS ANNEXES ANNEX 1. ARV Treatment Centres in Nigeria ANNEX 2 : National structures and processes for ARVs ANNEX 3: Facility Structures and Processes ANNEX 4: Outcome Indicators ANNEX 5: Reporting Format for Data Collectors

3 ACKNOWLEDGEMENTS We wish to thank the Federal Ministry of Health and indeed the Honourable Minister of Health for the opportunity to carry out this the study. Special thanks go to Dr Mohamed Belhocine, the WHO Representative for Nigeria for his support and technical input into the document. The Directors of Food and Drug Services Mr. R. K. Omotayo and the Director of Public Health Dr. Edugie A. Abebe for their support. Our sincere appreciation goes to the World Health Organisation at all levels with special reference to Mrs. Helen Tata of the Drug Action Program (DAP), Dr. Ogori Taylor, the Essential Drugs National Professional Officer for Nigeria and Dr. Niyi Ogundiran, the National Professional Officer for HIV for their immense technical support leading to the success of the study. We are grateful to Mr. O. G. Amosun, Deputy Director Food and Drug Services, Dr. Levi Uzono, National AIDS and STD Control Program and Dr. Catherine Adegoke, for their contributions in the realisation of this project. Special mention goes to the pharmacists in Food and Drug Services Department of the Federal Ministry of Health, Mrs. Eno A. Ubok-Udom, Mr. O. O. Omoyele, Mrs. A. O. Akinbisehin, Mrs. O. Idowu, Mr. E. O. Okibe, Mr. Y. O. Oloyede, Mr. Linus Odemena, Mr. T. T. Tile, MR. B. B. Otohabru, Mr. L. Fagbemiro, Mr. N. J. Joseph, and Mr. U. O. Ndukwe who collected data in all the treatment centres. 3

4 GLOSSARY ARVs ADRs AIDS ART CMS EDL FMOH HIV LDC NACA NAFDAC NASCP NEACA NGOs NIMR PLWHA PMTCT R&D STG TRIPS WHO Antiretrovirals Adverse Drug Reactions Acquired Immunodeficiency Syndrome Antiretroviral Therapy Central Medical Stores Essential Drugs List Federal Ministry of Health Human Immunodeficiency Virus Least Developed Countries National Action Committee on AIDS National Agency for Food And Drugs Administration and Control National AIDS and STD Control Programme National Expert Advisory Committee on AIDS Non governmental Organisations National Institute for Medical Research People Living with HIV/AIDS Prevention of Mother to child Transmission Research and Development Standard Treatment Guidelines Trade Related Aspects of Intellectual Property Rights World Health Organisation 4

5 EXECUTIVE SUMMARY Nigeria currently has an estimated 3.5 million People Living With HIV/AIDS (PLWHAs) and HIV seroprevalence level of 5.0%.. In January 2002, the Nigerian government commenced a programme to provide antiretroviral (ARV) drugs, at a subsidized rate, to ten thousand (10,000) People Living with HIV/AIDS, annually. The objective of this study was to conduct a rapid assessment of the use and management of ARV drugs in the treatment centres. The assessment was aimed at identifying pressing issues in program management that could hinder the achievement of ensuring the uninterrupted supply of good quality ARVs. In essence, the result of the study was to form the basis for management decision-making and re-engineering of the ARV drug programme. Using questionnaires as a tool for measuring indicators (structural, process and outcome indicators), data was collected from designated treatment centres in public health facilities. Patients and health managers were also interviewed at the 25 treatment centres established by the government. At the time the assessment was conducted in November 2003, a total of 11,435 persons were reported to be on the government program and 2,249 on other initiatives implemented at seven centres with drugs procured from the private sector. Eighty percent (80%) of the facilities had the three drugs - Nevirapine, Stavudine and Lamivudine - in stock. Forty four percent (44%) of the facilities did not have adequate stock balance of the three ARVs and eight (8) facilities had experienced stock out for periods ranging from one to three months. Expired ARVs were found in 64% of the facilities with the loss due to expiry estimated at $146,717 or 1 N19,953,510. One of the five consignments of ARVs received at the Central Medical Store had a shelf life of five months. 1 1 USD was equivalent to 136 naira at the time the study was conducted 5

6 Storage of ARVs was generally satisfactory in all the centres as 84% and 92% scored above the 50% required for adequacy of storage in the dispensary and the facility store, respectively. Only three centres provided drugs free of charge to patients; others recovered the full costs with or without including other administrative charges. The cost of a month s supply of an adult dose of the recommended triple combination of ARVs from the government program ranged from N1000 to N1,500 ($7.8 to $11.7) while an equivalent regimen from the other initiatives ranged from N 7,000 to N 14,000 ($54.7 $109.4). A person earning the minimum wage in Nigeria would work for 0 to 6 days to procure the stated regimen from the government initiative while (s)he would work for 30 to 90 days for the same month s supply of ARVs from the other initiative. Initiation of therapy at all the centres was done using a combination of clinical parameters, lymphocyte counts and CD4 counts. Services for measuring the CD4 count was available in all the centres but the cost varied from N600 to N 4,000 ($4.4 $29.4) per test and the frequency of determination varied from two to four times a year per patient. Affordability of tests was cited as a limiting factor to achieving the monitoring goals set by the facilities. While most of the facilities claimed to have monitored and reported adverse drug reactions, tracking of defaults and monitoring of resistance were hardly undertaken. Twenty six percent (26%) of the patients had experienced adverse drug reactions. Seventy-seven percent (77%) of the centres had the Standard Treatment Guidelines (STG) for ARVs but none had the recently reviewed National Essential Drugs List (EDL). Sampled prescriptions showed total adherence to the recommended triple therapy in all the centres. Eighty six percent (86%) of the labels on patients medications provided inadequate information but 97% of patients had adequate knowledge of how to take their drugs. Only 3% of patients experienced difficulties in following the treatment course. 6

7 It can, therefore, be concluded that the main barrier to accessing ARVs is financial. This, thus, necessitates the development of appropriate strategies to make the drugs more affordable since ARVs are funded mostly out-ofpocket. The strategies would include tax exemptions, a more realistic pricing policy, promotion of local production, exploring public private partnerships and other relevant global initiatives. Other areas requiring improvement include information management practices. This would ensure improved accountability for patients, drugs and testing kits as well as provision of relevant information needed for optimisation of program management. Procedures for HIV tests, confirmatory tests and measurement of CD4 counts were well established in the centres; but issues of affordability and harmonisation of testing policies still need to be addressed. The goal of an ART program, which is to provide uninterrupted drug supply to treatment centres and to patients in a timely manner, while minimising drug expiry, was not achieved. In fact, the study revealed poor management of drug supply. There is, thus, the need to evolve effective drug procurement, distribution, financing and ARV information management systems to improve access and affordability of ARVs. To further promote the rational use of drugs, ARV STGs need to be reviewed, printed and, together with the revised 2003 EDL, made available to relevant health facilities. To minimise adverse drug reactions and development of resistance, health professionals in the centres need to be trained on rational use of ARVs, as well as appropriate ARV dispensing techniques; especially with respect to labelling and rational patient enrolment practices. 7

8 *Ado Ekiti Anambra State *Owerri *Enugu COUNTRY BAKGROUND Nigeria : demographic information Nigeria is the 10 th most populous country in the world and the most populous country in sub-saharan Africa. The last official census conducted in 1991 put the population at about 88.9 million. Projections indicate that by the year 2003, there would be about 126 million people living in Nigeria. With a land area of 923,768 square kilometres, the population density is about 96.3 persons per square kilometre. Nigeria s growth rate is estimated to be 2.8% per annum. HIV/AIDS in Nigeria MAP OF NIGERIA SHOWING STATE TO STATE PREVALENCE HIV Prevalence per State end of 2003 and States with ARV Centers *Abeokuta *Ibadan 4.7% *Ikeja *Birnin Kebbi Sokoto State 4.5% *Sokoto Kebbi State 2.5% Kwara State 2.7% Oyo State 3.9% 1.5% Ogun State * Lagos State *Ilorin *Gusau Zamfara State Niger State 7.0% 3.3% *Minna *Lokoja *Osogbo Ekiti State 5.7% 1.2% 2.0% Kogi Osun State State *Akure 2.2% Edo Ondo State 4.9% State 4.3% 3.3% Enugu State *Benin *Asaba City 5.0% Delta State *Yenagoa 4.0% Rivers Bayelsa State State 6.6% *Port Harcourt Katsina State *Awka 3.1% IAbia Imo State State *Katsina 2.5% *Kano Kano State 4.1% *Kaduna Kaduna State 6.0% ** ** FCT 8.4% Nasarawa State 6.5% 3.7 % *Lafia 7.2% *Uyo Akwa Ibom State *Makurdi Benue State Jigawa State *Jos 12% Cross River State *Calabar 2.0% *Dutse Bauchi State 4.3% 6.3% Plateau State 9.3% *Bauchi Taraba State Ebonyi State Yobe State Gombe State 6.8% *Gombe *Jalingo 6.0% 3.3% *Damaturu *Yola Borno State Adamawa State 7.6% 3.2% *Maiduguri < 5% 5-7% 7-12% + 7.2% ARV Centers * ** Lagos Has 3 ARV Centers Abuja Has 7 ARV Centers MO-ARVS NASCP FMOH 15th June 2004 Since 1986 when the first AIDS case was reported in Nigeria, the disease has since grown to epidemic levels with rapidly increasing prevalence rates of 1.8% in 1993, 3.8% in 1994, 4.5% in 1996, 5.4% in 1999, 5.8% in 2001 and 5% in 2003 based on HIV/Syphilis sero-prevalence sentinel surveys among women attending antenatal clinics. It is estimated that about 3.5 million Nigerians are infected with HIV/AIDS. 8

9 The most common modes of transmission are heterosexual intercourse, mother-to-child transmission and through contaminated blood and blood products. The epidemic has grown beyond the high-risk groups to the general population. Although some parts of the country are more affected than others, all states record more than 1% prevalence. In 2003, prevalence rates ranged from 1.2% in Osun State to 12% State in Cross River State. Nationally, prevalence is higher in urban than in the rural populations. Persons between the ages of are the most affected although in the South-south and South-west zones, the prevalence is highest among the age group. In 1987, the National Expert Advisory Committee on AIDS (NEACA) was inaugurated as the health response to the report of the first AIDS case in By 1988, the National AIDS and STDs Control Program (NASCP) was established with the mandate to coordinate all HIV/AIDS activities at national and state levels. In 1997, a Presidential committee on AIDS - the National Action Committee on AIDS (NACA) was established to implement the multisectoral response to the epidemic. Thus, Nigeria has passed through several phases in its response to the epidemic; starting from initial denial to a health sector response focusing primarily on prevention, and finally to a multisectoral approach. ART program in Nigeria Service delivery commenced in January 2002 in 25 tertiary health facilities (annex 1) distributed all over the country. From each of the sites, personnel including doctors, pharmacists and laboratory staff were trained to manage and monitor ARV treatment in the country. The centres commenced with a standard regimen of Stavudine, Lamivudine and Nevirapine with the aim of treating 10,000 adults and 5,000 children yearly. The Federal Government obtained a negotiated price of $350 for the triple therapy from Cipla. At the start of the program, the Federal Government procured the recommended triple regimen to treat 8,000 persons in the first year. The centres registered 25 patients each between February and June 2002; except 9

10 the National Institute for Medical Research (NIMR) that registered 50 patients. The program was later expanded to accommodate more patients ( an additional 100 to 500) based on the capacity of the individual centres to care for more PLWHAs. 10

11 INTRODUCTION TO THE STUDY Study Objective The objectives of the study are: To assess structures and processes available in Nigeria to enhance access to ARVs To evaluate management of antiretroviral drugs in the treatment centres To assess rational use of antiretroviral drugs in the treatment centres To determine pressing operational/technical issues that would impact on the goal of ensuring uninterrupted supply of good quality ARVs and adherence to the drugs. To formulate evidence based interventions to improve ARV use and management METHODOLOGY Structural and Process Indicators Two (2) structured questionnaires (annexes 2 & 3) were utilised to measure national and health facility structures and processes that would ensure access to good quality, affordable, safe antiretroviral drugs and kits. The national indicator questionnaires were administered to the national authorities namely the National Agency for Food and Drugs Administration and Control (NAFDAC), the Department of Food and Drug Services and the Federal Ministry of Commerce. The facility questionnaires were completed by the clinicians in charge of the ART programs, where they were available, or others in the program. Drug Management and Rational Use of Drugs The following indicators were measured in the 25 treatment centres. Access Percentage availability of ARVs listed in the treatment guideline Average stock out duration Affordability of ARVs Affordability of laboratory services Pricing and financing of ARVs 11

12 Rational Use Percentage of facilities with STG Percentage of facilities with EDL Percentage of drugs adequately labelled Percentage of patients who have adequate knowledge of how to take their ARVs Percentage of patients with adverse drug reactions Percentage of patients that have switched therapy Percentage of prescriptions according to national treatment guidelines Quality Adequacy of storage Percentage of expired drugs The data collectors received a briefing on the HIV/AIDS situation in Nigeria and were trained on data collection techniques. The instruments were pretested in two of the facilities located in Abuja. The tools were discussed and necessary modifications made. Thirteen (13) pharmacists working at the Food and Drugs Department of the FMOH carried out the facility level assessment. The facilities were grouped into zones and pairs of data collectors were assigned to collect data between November 10 and November 24, Twenty-five tertiary facilities implementing the government program were included in the assessment. Introductory letters from the FMOH were sent to each of the targeted facilities explaining the purpose of the assessment and enlisting their commitment to the study project. Data was compiled from facility records, prescriptions, stock cards and from interviews with program managers and patients. The data was entered in a spreadsheet and frequencies were manually calculated. Scope and Limitations The findings of this study are indicator-based and provide a cursory appraisal of the system; not a detailed evaluation. 12

13 Some of the officers responsible for the programs were not actively involved in the day to day management of PLWHAs and these were sometimes respondents to the questionnaires. Supplier performance records were not kept and it was therefore difficult to ascertain the validity of causes of stock-outs indicated by managers. It was difficult to distinguish between expiry caused by poor stock management from those caused by near expiry drug supply. Information about type and management of adverse drug reactions was elicited from one clinician per centre who responded to the questionnaires. More detailed information would require further investigations. It is doubtful if respondents fully comprehended the meaning of medication profile, resistance monitoring and default tracking. In addition, claims of keeping them were not backed by records. Data on number of health personnel who treat PLWHAs was not used to establish health worker/patient ratio since it was difficult to determine health workers who manage patients during clinic days. RESULTS National Level Structures and Processes Regulatory status of ARVs in Nigeria NAFDAC, which is the national drug regulatory authority in Nigeria, commenced listing of ARVs in To date, there are a total of 25 ARVs listed; 9 are innovation products and 16 are generics (annex 4). ARV registration, including its fast tracking, falls under the general guidelines governing registration of ethical medicines. It costs N 250,000 ($1,953) to register and to renew the registration of an ARV. The NAFDAC laboratories in the country are well equipped to undertake analysis of ARVs. Essential Medicine List The Essential Medicines List for Nigeria was updated in 2003 to include 8 antiretroviral drugs Didanosine, Lamivudine, Stavudine, Zidovudine, 13

14 Efavirenz, Nevirapine, Indinavir, Nelfinavir and fixed dose combination of Lamivudine, Stavudine and Nevirapine. ARV supply system While there are many importers of ARVs in the country, only Cipla and Ranbaxy have supplied ARVs to the public sector. ARVs are centrally procured by the government and warehoused at the Central Medical Store at Oshodi, Lagos. Initially, courier companies were utilised for the distribution of ARVs to treatment centres. However, due to non-availability of funds to pay the courier companies, the health facilities were then directed to collect their allocations of ARVs from the Central medical stores in Lagos. Suppliers were able to fulfil government orders. An error in the 2003 budgeting process led to delays in the release of funds for the procurement of ARVs. Seven (7) centres also procure medicines from private sector suppliers to dispense to patients that are not on the government program. ARV financing Procurement of ARVs has been solely financed by the government. The sum of about N1 billion ($7.6 Million) was spent on ARVs from ; and N1.5 billion ($11.4 million) had been budgeted for the procurement of ARVs in ARVs are subsidised for patients on the government program. Patients are charged a fixed rate of N1,000 or $7.8 for the triple therapy per month. Since the national health insurance scheme is not yet fully operational, the status of ARVs in the scheme cannot be ascertained. Imported ARVs are taxed like any other pharmaceutical. A total of about 30% tax is levied on imported ARVs destined for the private sector (including NGOs), while government procures ARV supplies are tax-free. Like other pharmaceuticals in the country, there is no pricing policy guiding sale of ARVs in the public sector, private sector and NGOs, and which sets maximum wholesale mark-up and maximum retail mark-up. 14

15 Access to ARVs Although ARVs are widely available in private drug distribution channels, no national indicator study has been carried out on access to ARVs. The extent to which health facilities in the private sector are involved in the delivery of ARVs is unknown. Rational use of ARVs A national standard treatment guideline for ARVs was first produced in 2001 and plans are underway to review it. There is also a treatment guideline for tuberculosis but there is none for other opportunistic infections. There are independently funded and obligatory continuing education programs for health professionals; but ARV use is not yet included in these curricula. There have been no public education campaigns in rational use of ARVs by either the FMOH or NGOs. Non-commercially funded national drug information centres that provide unbiased ARV information to health professionals, counsellors and consumers, do not exist Intellectual property rights Nigeria, like other members of the World Trade Organisation is currently reviewing her intellectual property laws. Since Nigeria is not classified among the Least Developed Countries (LDC), the Trade Related Aspects of Intellectual Property Rights (TRIPS) agreement comes into effect in The appropriate laws, which would incorporate recommendations of the TRIPS agreement and safeguards, in line with Doha declaration, are currently being discussed in the different arms of the legislative system, before they are passed into law. Facility Level Structures and Processes All the centres included in the study were public health facilities operated and funded by the government. ARVs were initiated through a government program which combines Stavudine, Lamivudine and Nevirapine procured and supplied to the facilities at a subsidised rate. These are then dispensed to a specified quota of patients per centre. Twenty eight percent (28%) of the 15

16 centres also procure drugs from the private sector notably Ranbaxy and Cipla - at a much higher price than that offered to the government to cater for patients who cannot be accommodated on the government program. The initial supplies of ARVs for the national program were made from the Central Medical Stores to the facilities by means of courier services. Subsequently, the facilities have been responsible for transporting their supplies from the Lagos depot. Personnel Recruitment of personnel was not made specifically for the purpose of the care of HIV/AIDS patients. However, certain full time staff already working in the facilities were dedicated to the care of HIV/AIDS patients. Most of the facilities also have special clinic days dedicated to PLWHAs. Continuing education has been provided to 57% of the doctors, 54% of nurses, 45% of pharmacists, and 53% of counsellors involved in the provision of ART in the centres. Patients A total of 11,435 persons were reported to be on the government program, while about 2,249 were on other initiatives whereby the facilities provided unsubsidised ARVs to patients. The sex profile of patients on the government program indicated that 49% were males and 51% females. Only 47% of the facilities were able to report on the age distribution of current and transferred patients. Fifty six percent (56%) of the facilities could provide information on the number of patients that had discontinued treatment due to death in the 12 months preceding the study. However, only 28% were aware of those who discontinued due to lack of financial resources and only 16% could make a statement on patient discontinuation of therapy due to lack of stock at the health facility. 16

17 Treatment and testing All the centres reported initiating treatment based on clinical parameters, CD4 and lymphocytes counts. Only four centres initiated treatment based on viral load in addition to CD4 and lymphocyte counts. All the facilities had laboratories for measuring CD4 counts but only two facilities had laboratories for viral load determination. In 17% of the facilities, CD4 count results were obtainable in less than 24 hours. In 67% of facilities, results could be obtained between 24 and 48 hours while in another 17% of facilities, results could take up to seven days. Results of viral load counts were obtainable within seven days in two centres, within 21 days in another centre and 30 days in yet another centre. Sixty one percent (61%) of the facilities had a policy of carrying out CD4 counts four times in a year, 17% of facilities did this three times a year and 22% twice a year. The main constraint to achieving these set targets was affordability as reported by all the centres. A few identified the additional constraint of unreliability of results (two centres) and lack of reagents (one centre). Methods of payment In 22 out of the 25 centres, patients paid for ARVs and other HIV/AIDSrelated medicines out-of -pocket. Monitoring and reporting Ninety four percent (94%) of the centres claimed to be monitoring side effects of ARVs, while 72% claimed to be reporting side effects. While 60% of the centres claimed to be monitoring resistance, 38% claimed to be reporting such observations. Eighty nine percent (89%) said they maintained medication profiles of patients on ARVs while 11% admitted not keeping such records. 82% of the facilities claimed to have instituted a method for recording defaults while the rest reported not having such a system. Only about 29% reported tracking defaulting patients. 17

18 Outcomes Access Table 1: ARV Drugs Stock Assessment Drug Manufacturer (Generic) In stock Appropriate Stock Balance Expired Qty expired No % of No % of No % of No % of No (by 60s) facilities facilities facilities facilities NEVIRAPINE ,188 STAVUDINE ,934 LAMIVUDINE ,553 At the time of assessment (November 2003), 80% of facilities had the three ARVs in stock. Eighty-eight percent (88%) had both Nevirapine and Stavudine in stock, while 92% had Lamivudine in stock. Stock management was inadequate, as 44% did not have accurate stock balance and 60% of these facilities had expired drugs. A total of 7,188 packets of Nevirapine were found expired in 60% of the facilities, 2934 packets of Stavudine in 28% of the facilities and 6,553 packets of Lamivudine in 40% of the facilities. Nevirapine was the most affected and Stavudine the least. These represent a total loss of $146,717 or 2 N19,953,510 due to expiry. 2 1 USD is equivalent to 136 naira 18

19 Figure 1: Stock out Duration of Antiretroviral Drugs STOCK OUT DURATION 4.5 NUMBER OF FACILITIES Nevirapine Stavudine Lamivudine < 30 DAYS DAYS DAYS > 90 DAYS Eight (8) facilities (32%) had suffered stock out of some or all of the three ARVs since the inception of the program. Stock out duration for the three ARVs ranged from less than one month to more than three months. The main reason for stock outs was inadequate supply of drugs from the program. During the stock out period, patients were asked to procure drugs from other sources such as the private sector (profit and non-profit) or they were offered drugs from the parallel program, where such programmes existed. Affordability of the Triple Combination (Stavudine, Lamivudine and Nevirapine) Table 2a: Cost of ARV Drugs to Patients (Government Initiative) Total Cost to patient per 0 N1-N999 N1000 >N >N1250 TOTAL visit per month N1250 Adults %age of facilities 12% 0% 64% 20% 4% 100% Table 2b: Cost of ARV Drugs to Patients (Other Initiative) Total Cost to patient 0 N1001 N1250 N1501 N7,000 >N10,000 N/A 3 Total per visit per month N1250 N1500 N6999 N10,000 Adults % age of facilities 0% 0% 0% 0% 20% 8% 72% 100% 3 Centres that have only the government program 19

20 From the assessments, 16 (64%) of the centres supplied the patients the triple combination of ARVs at N1,000 under the government-funded program. With the added costs of hospital cards, and consultation fees in some cases, five centres (20%) supplied the drugs at costs ranging between N1,030 and N1,250 ($7.8 $11.7). While one of the centres recorded a 50% mark up on the price, twelve percent (3) provided ARVs free of charge to patients. Supply of ARVs to children was almost non-existent as 21 (84%) centres had no supply system for children. Of those that provided ARVs to children, none gave them free of charge. The centres provided ARVs to children at prices ranging from N600 to N1,250 per month. The Prevention of Mother-to-Child Transmission (PMTCT) was offered in 10 of the 25 centres. Of these, six (60%) gave Nevirapine free of charge, while the rest charged between N1000 and N1250 ($7.8 $9.2). Of the 7 centres offering other drug initiatives to adults, the cost of these drugs was between N7,000 N10,000 ($54.7 $73.5) in 5 (81%) centres, and greater than N10,000 ($73.5) in the 2 (21%) others. For children, the cost was between N1,500 and N7,000 in 57% of centres offering other initiatives. In the absence of supplies of ARVs for children on the government initiative, some centres prepared ARV syrups extemporaneously, using the available tablets. It is doubtful whether this practice is appropriate for ARVs. Table 2c: Affordability of ARV Drugs to Patients (Government Initiative) Number of Days >7.0 TOTAL Work Adults % age of facilities 12% 0% 72% 12% 4% 100% Table 2d: Affordability of ARV Drugs to Patients (Other Initiatives) Number of Days >90 Total work Adults % age of facilities 0% 0% 0% 0% 0% 0% 71% 29% 0% 100% Of 464 patients, 443 (95%) obtained their drugs out-of-pocket, while 21 (5%) obtained their drugs at no cost to them. A person earning the minimum wage 20

21 in Nigeria would work for 0 to 6 days to procure one month s supply of drugs from the government initiative while he would work for 30 to 90 days for an equivalent supply of ARVs from the private initiative in the same centre. Affordability of laboratory services 1. Cost of a single HIV TEST 0 <N500 N500-N999 N1000 N1,500 N/A Adults %age of facilities 16% 16% 56% 8% 4% 0% 2. Cost of a single HIV CONFIRMATORY TEST: 0 <N1,000 N1,000-N1,999 N2,000-N2,999 N3,000-N5,000 N/A Adults %age of facilities 20% 12% 20% 12% 16% 20% 3. Cost of a single CD4 COUNT determination: 0 <N1,000 N1,000-N1,999 2,000-2,999 N3,000-N5,000 N/A Adults %age of facilities 4% 4% 0% 44% 48% 0% 4. Cost of a single VIRAL LOAD determination 0 2,500 5,000 N9,000 10,000 20,000 N/A Adults %age of facilities 4% 0% 16% 8% 4% 4% 64% 5. TOTAL ANNUAL COST OF ALL LABORATORY TESTS 0 <N2,000- N5,000- N10,000- N20,000- > N40,000 NA N4,999 N9,999 N19,999 N40,000 Adults %age of facilities 4% 12% 24% 24% 20% 12% 4% There were wide differences in the cost of the various laboratory tests. Annual cost of tests including HIV tests, confirmatory tests, CD4 and viral load counts ranged from 0 to N56,500 ($415.4). One centre offered the tests free of charge, 11 centres charged less than N10,000 ($73.5) while 14 centres charged between N10,000 to N56,500 ($ $415.4). Facilities for measuring CD4 count were available in all the centres but the cost varied from N600 to N 4,000 ($4.4 $29.4) per test. The number of times CD4 counts were carried out also varied from two to four times a year per patient. Facilities to determine viral load were available in only two centres. 21

22 Rational Use of ARVs Figure 2: Patient Care Indicators 120 Percentage of patients Paid out of pocket Adequate label Adequate knowledge 1 Number of tim es treatm ent w as changed Patient has had Adverse drug reactions 3 Patient has found it difficult to follow treatment course Seventy-seven percent (77%) of the centres had the Standard Treatment Guidelines for ARVs. In all the centres assessed, the recommended triple therapy regimen was being prescribed for virtually all patients. Only one centre had a prescription of a non-recommended triple regimen and two had a double regimen. No facility offered a mono-therapy, based on the adult prescription sheets sampled. The recently reviewed EDL was not available in any of the facilities. The labelling of ARV drugs, which should include the name of the ARV, name or code of patient, frequency and duration of administration, was inadequate in 86% of cases. However, most patients (97%) had adequate knowledge of their drug regimen. Only three percent (3%) of the patients had experienced difficulties in following the course of treatment and only 1% of the patients had had cause to change the treatment regimen. Twenty six percent (26%) of the patients had experienced adverse drug reactions (ADRs). A vast majority of the reported cases of ADRs was due to Nevirapine. The most commonly reported adverse drug reactions were rashes and itching; with fewer patients experiencing mild reactions such as boils, yellowish eyes, diarrhoea, nausea, vomiting, loss of appetite, insomnia, swollen face, headache, weakness, 22

23 peeling of the skin, jaundice, goitre-like swelling, ankle swelling. Some patients also experienced severe reactions such as Steven Johnson s syndrome, peripheral neuropathy and jaundice. Management of adverse drug reactions included use of antihistamines in 12 centres, reduction in the dose of Nevirapine in seven centres, use of corticosteroids in two centres, withdrawal of Nevirapine and use of double therapy in three centres. In two centres, patients were counselled that the ADR would subside with time, while in another two centres, Nevirapine was suspended and reintroduced. One centre treated ADRs with dermatological creams. It was in only one centre that the clinician substituted Nevirapine with Efavirenz. Quality Shelf life of Consignments Received Between 2001 and 2003 at the Central Medical Stores, Oshodi. Drug Shelf life (months) Number of consignments Nevirapine Stavudine Lamivudine Although storage of ARVs was generally satisfactory, 84% and 92% of facilities met more than 50% of the requirements in their dispensaries and stores respectively. Only two (8%) had temperature charts in their refrigerators. 11 (44%) of the centres arranged drugs on the floors and 20% of the centres had inadequate storage space. In six centres (24%), drugs were not adequately protected from sunlight. The situation in the dispensing rooms was identical to that in the storage room but drug arrangement was inadequate in addition to the already identified storage requirements. 23

24 Five consignments were received at the CMS between 2001 and 2003; of which one (1) had a shelf life of 5 months. DISCUSSIONS National Structures and processes Processes for regulation, control, rational selection, and supply of ARVs are already in place in the country since ARVs do not need separate structures for such activities. The regulatory authority is however, still listing ARVs. Given the specialised technical knowledge required for clinical trials and bioavailability studies of ARVs, and the danger that supplies of counterfeit ARVs pose to patients, there is an urgent need to build capacity in quality analysis of ARVs. The supply of ARVs is well developed through importation of ARVs from generic and R&D companies into the country. However, ARVs are still unaffordable from the private sector. There is need to explore different approaches such as removal of taxes, evolving a pricing policy and exploring different global initiatives to improve affordability. The government has been the only source of financing for ARV purchase in the public health facilities. However, the capacity to take care of as many patients as possible is limited due to the unavailability of funds to procure ARVs. It is hoped that with the opportunity to access funds from the Global Fund for Malaria, AIDS and Tuberculosis, more PLWHAs would benefit from the program. Since the health insurance scheme in Nigeria is not yet fully operational, and patients are still left to purchase ARVs out-of-pocket, making ARVs from the private sector affordable is still the option for ensuring sustainable supply. Exploring public private partnerships in the provision of ARVs may also yield the desired results. Pharmaceutical suppliers could provide initial stock to the Central Medical Store from where various facilities would purchase needed supplies. These facilities would in turn maintain drug revolving funds to sustain supply of drugs to PLWHAs. 24

25 Facility structures and processes The ARV treatment centres have qualified personnel for the delivery of care and support to PLWHAs. However, only half of them benefited from continuing education in the year preceding the study. Yet, training is crucial in ensuring appropriate quality of care of PLWHAs. Determination of HIV tests, confirmatory tests and measurement of CD4 counts were well established in all centres and most of them carried out these tests in a timely manner. There was, however, a wide variation in testing policies and cost of tests from facility to facility. There is room for improvement regarding the affordability of tests and harmonisation of policies. Most of the centres could provide information on the total number of patients in their respective programs but could not disaggregate the data based on variables such as age groups, defaults, transfers, number of patients who could not afford the drugs, number of deaths etc. Information regarding resistance to drugs, adverse drug reactions, recording and tracking of defaults was vague. A well-defined data collection system that would account for patients and medicines and provide information needed for program management is essential. Access and quality The goal in any ART program is to provide uninterrupted drug supply to treatment centres and to patients, in a timely manner while minimising drug expiry. To achieve this, an efficient drug supply management system is required at the centres. Such a system would ensure accurate quantification of drug needs and constant communication between the central supply system and the facilities; to prevent stock outs and ensure redistribution of about-to-expire drugs. The government made a laudable effort in procuring the initial stock needed to treat 10,000 adults but unfortunately, at the time of the study; drug supply had fallen to an undesirable level. This could be attributed mainly to weak drug management structures as well as poor, procurement and patient recruitment practices. 25

26 The drug management system was found to be inadequate, as drug allocation to centres seemed to have followed a push rather than a pull system. Some centre managers complained of receiving drugs which did not meet the needs of their patient loads while program managers observed that the centres recruited a lot more patients than they were authorised to. Overall, there seemed to be lack of communication between the central supply system and the centres, as well as between centres. This was evidenced by the fact that while some centres experienced stock outs, others recorded expiries. It was also observed that the centres still stocked only first line triple therapy despite the fact that second line regimens were available at the central medical store! The storage conditions in the stores and dispensing areas were found to be generally adequate. This may be due to the fact that facilities are located in tertiary health institutions and as such, drug storage is handled in wellestablished pharmacies run by professionals. Data recording is not routinely made in terms of exact age of children in most health facilities. This reduces the usefulness of data gathered. For drugs like ARVs, it not acceptable to dispense to patients without keeping detailed records of transactions such as prescriptions, stock cards, patient data etc. Given the high value of ARVs, it is important that the drugs and other commodities be properly accounted for. Drug procurement at the central level was also not in consonance with drug needs at the centres. Often, release of funds was delayed, especially for subsequent purchases of ARVs, following the initial stock. The shelf lives of all consignments of procured ARVs were shorter than two years. In fact, the shelf life of one consignment was as low as five months. This markedly reduced availability to the patients while accentuating loss due to drug expiry. Also, the recruitment practices in which centres registered patients beyond the allotted quotas further exacerbated the problem of drug availability. 26

27 On the surface, it would seem that the government drug programme requiring a patient on minimum wage to exchange the equivalent of six days pay for a month s supply of drugs, is affordable. But when put into context and bearing in mind the fact that the poorest households in Nigeria spend about 90% of their income on food alone, it is clear that even the government initiative is not affordable. The assumption, in fact is that only one member of the family would receive treatment at a time. The sad reality is that some families have more than one PLWHA and, therefore, more than one recipient of the drug therapy. It is worthy of note that of about 450,000 PLWHAs who need antiretrovirals, about 10,000 persons have access to the government program. The rest of PLWHAs who require ARVs have only one option open to them - procuring from the private sector. Yet, to procure a month s supply of drugs from this sector, a person on the minimum wage would be required to work for more than two months. Rational use of drugs Laudable attempts have been made by managers to follow the triple therapy regime, which is in the standard treatment guideline. However, the STG needs to be reviewed and second line drugs included in it. No centre had the newly reviewed and printed 2003 edition of the EDL that contains ARVs since these are yet to be distributed. Patient recruitment practices showed poor appreciation of rational use of ARVs. If managers understood that once a patient commences therapy, it should not be interrupted, then they will not include and exclude patients at will. Labelling of medicines dispensed to patients was inadequate. In an attempt to maintain anonymity, most dispensers omitted the names of drugs and patients. Use of codes would still have provided both the desired anonymity and conformity to appropriate labelling requirements. Most of the patients had adequate knowledge of their medication. The rate of adverse reactions to ARVs was quite high. Availability of substitutes as well as proper monitoring systems could have reduced the 27

28 rate and severity of some of these reactions. Specific guidelines on management of common ADRs such as itching and rashes was not in place. The occurrence of severe adverse drug reactions such as Steven Johnson s Syndrome accentuates the need for second line drugs in the facilities. Unfortunately, some clinicians resorted to prescribing double therapy regimes in response to ADRs even though the medical stores had stocks of relevant substitutes. The high cost of relevant tests may limit adequate monitoring of therapy. This in turn would impact on areas such as assessment of drug effectiveness and detection of the development of drug resistance. The wide variability in policies and practices such as in the management of adverse drug reactions, drug monitoring practices, and mark up for ARVs may be attributed to the quality of guidelines provided to the centres. Indeed the guidelines are quite rudimentary and lack clear guidance on most of the issues encountered in the day to day implementation of the ART program. It will therefore be needful to undertake a comprehensive review in order to make it more relevant to program implementation needs. RECOMMENDATIONS The following are recommended in order to improve access to antiretroviral drugs to PLWHAs in the treatment centres 1. There is need to build the capacity of staff of drug regulatory authorities in fast track registration and quality analysis. 2. Efficient drug supply and management systems need to be institutionalised to eradicate stock outs and minimise drug loss through expiry. 3. Mechanisms to ensure affordable pricing of drugs and laboratory services need to be explored. Strategies to employ may include price negotiation with pharmaceutical suppliers, pricing information dissemination, local manufacture, regional bulk procurement etc. 28

29 4. There is need to review ARV standard treatment guidelines to include second line medicines, drugs for opportunistic infections, drug therapy monitoring and management of ADRs to ensure quality of patient management. 5. Ground rules on recruitment of patients need to be developed and strictly adhered to ensure rational use of ARVs and minimise non-availability of drugs. 6. Rational use of ARVs should be strengthened among professionals involved in the program to enhance appreciation of appropriate ARV use practices. 7. Management Information Systems need to be developed for collection, collation and processing of data for the purpose of program monitoring and decision-making. 29

30 ANNEXES ANNEX 1. ARV Treatment Centres in Nigeria SN CENTRE 1. Ahmadu Bello University Teaching Hospital, Zaria 2. Aminu Kano Teaching Hospital, Kano 3. Aso Rock Clinic, Abuja 4. Central Bank of Nigeria Clinic, Abuja 5. Creek Military Hospital, Lagos 6. Federal Medical Centre, Gombe 7. Federal Medical Centre, Makurdi 8. Federal Medical Centre, Owerri 9. Federal Medical Centre, Uyo 10. Gwagwalada Specialist Hospital, Gwagwalada 11. Jos University Teaching Hospital, Jos 12. Lagos University Teaching Hospital, Lagos 13. National Hospital, Abuja 14. National Institute for Medical Research, Lagos 15. National Institute for Pharmaceutical Research and Development, Idu, Abuja 16. Nnamdi Azikiwe Teaching Hospital, Nnewi 17. State House (DSS) Clinic, Abuja 18. State House (NIA) Clinic Abuja 19. University College Hospital, Ibadan 20. University of Benin Teaching Hospital, Benin City 21. University of Ilorin Teaching Hospital, Ilorin 22. University of Maiduguri Teaching Hospital, Maiduguri 23. University of Nigeria Teaching Hospital, Enugu 24. University of Port Harcourt Teaching Hospital, Port Harcourt 25. Uthman Dan Fodio University Teaching Hospital, Sokoto 30

31 ANNEX 2 : National structures and processes for ARVs Country name: Date: Informant: Position: Contact Details: A. Regulatory status 1. How many ARVs are registered by the national Branded medicines regulatory authority? Please attach a list. 2. How much does it cost to register an ARV? Branded New registration: Renewing registration: 3. Is it possible to analyse the quality of ARVs within the country or is it necessary to send them to an external laboratory? Quality tests done at a national lab: Quality tests done at external lab: Don t Know Don t Know Always/sometimes/never Always/sometimes/never Generic (INN) Generic (INN) Don t Know Don t Know B. Essential Medicines List (EML) 4. a) Has the national essential medicines list (EML) been revised to include ARVs? b) If yes, when was it most recently updated? c) How many ARVs are included on the EML? 5. Which of the following ARVs are included on the EML: Abacavir (ABC): Didanosine (ddi): Lamivudine (3TC): Stavudine (d4t): Ziduvodine (ZDV or AZT): Efavirenz (EFZ): Nevirapine (NVP): Indinavir (IDV): Ritonavir: Lopinavir/low dose Ritonavir (LPV/r): Nelfinavir (NFV): Saquinavir (SQV): Others (please attach a list of other ARVs on the EML): C. Medicines supply system 6. How many suppliers supplied ARVs to the country in the most recent year for which data is available? 7. What is the total national annual budget for medicines and the year of the data? 8. What is the total national annual budget for ARVs and the year of the data? 9. How is national procurement of ARVs financed? Regular government budget: Loan: Global Fund: Other forms of aid: 10. How many ARVs from the WHO prequalification list are procured? Year Branded Branded Year US$ Year US$ Year Don t Know Don t Know Don t Know Generic Generic % % % % Don t Know Don t Know Year Percentage of Don t total cost Know 31

32 11. What is the value of ARVs procured in the most recent year for which data is available? Branded Don t Know Generic Don t Know Year Year 12. Are suppliers able to fill national orders? 13. How often are national orders for ARVs submitted to suppliers? Every months 14. Are ARVs integrated into the public sector medicines supply system? F. Medicines financing 15. Are patients charged a nationally fixed rate for ARVs at public health facilities? If yes, indicate rate in US$, write 0 if free of charge. 16. Health insurance: (Health insurance is any prepayment scheme for health care costs additional to but excluding subsidies funded through the Ministry of Health budget.) Are ARVs covered by health insurance? US$ Public Don t Know Private Emplo yer Provid ed Don t Know Don t Know Of those ARVs covered, what percentage of the cost is covered? % % 17. What are duties, taxes, and levies assessed on imported ARVs? Public Sector % Don t Know Private Sector % Don t Know % NGOs % Don t Know G. Rational use 18. a) Are there national standard treatment guidelines for ARVs? b) If yes, when were they last updated? c) Do the guidelines cover treatment for: Adults: Children: Please attach copies. PMTCT: 19. Within the last 12 months, how many of the following professional participated in a continuing education programme on ARVs (not including commercially-funded programmes): Doctors: Nurses/midwives/paramedical staff: Pharmacists: Pharmacy aides/assistants: Counsellors: 20. Is there a non-commercially-funded national drug information centre that provides information on ARVs on demand to: Prescribers: Dispensers: Counsellors: Consumers: I. Intellectual property rights protection and marketing authorization 21. Are there restrictions on the import of generic ARVs? 22. TRIPS Agreement (Agreement on Trade Related Aspects of Intellectual Property Rights): 32