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close this bookCote d'Ivoire Ministry of Health - UNAIDS HIV/AIDS Drug Access Initiative - Preliminary Report (UNAIDS, 2000, 22 p.)
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View the documentIntroduction
View the documentObjectives - Program evaluation
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Results

1. Description of sociodemographic and health status characteristics of all patients evaluated for eligibility to participate in the UNAIDS/MOH Drug Access Initiative.

1.1 - Socio demographic characteristics

1.1.1 Number of patients accessing the eligibility screening

As of March 31, 2000, 2144 patients presented to the accredited centers for eligibility screening. The number of patients attending the accredited centers for the first time since the beginning of the initiative is summarized in Fig 1. This number includes patients who were already on ARV therapy prior to the UNAIDS/MOH initiative but who joined the initiative because of drug price reduction; 270 drug-experienced patients joined the Initiative of whom 222 were taking ARV therapy at the time of this evaluation. An average of 113 new patients presented to the clinics each month. However, in December 1998, a relatively small number of patients attended the clinics. In contrast, the number of attendees exceeded 150 both in April and May 1999.

1.1.2 Clinics accessed and basic demographics

Men have been marginally in excess among those accessing the initiative. Most have been Ivorian citizens residing in Abidjan (see table1).


Fig 1. Number of patients attending the eligibility screening in the UNAIDS/MOH Drug Access Initiative in Cd'Ivoire, as of March 2000

Table 1. Number of patients (N=2144) by center and their characteristics

Characteristics

N

Percent

Female

1038

(48)




Clinics




TB clinic Adjame

807

(37)


Infectious Diseases Department

585

(27)


USAC clinic

379

(18)


CIRBA clinic

183

(9)


Military Hospital

99

(5)


Pediatrics (Yopougon)

91

(4)

Ivoirian citizenship

1883

(87)

Residing in Abidjan

1638

(76)




1.1.3 Age

Overall distribution by age group is shown in Fig 2: the majority of patients have been between 20 and 49 years old. Of those 20 years of age or older, the mean age was 36 years (range 20-83). The percent of patients under 20 years of age is approximately 5%: and among them, 20% were less than 5 years old. Of those under 20 years of age, the mean age was 7 (range 1 month-19).


Fig 2: Age group distribution among patients accessing the UNAIDS/MOH Drug Access. Initiative in Cd'Ivoire, August 1998-March 2000 (N=2144)

1.1.4 Economic and professional characteristics

There are a number of characteristics that may indirectly indicate economic status of patients, such as the household daily food expenditure. Approximately 55% of patients spend between 2 and 5 US dollars daily for the food of the entire household.

The chart below represents the distribution of salary or monthly income of patients presenting for eligibility screening. Of these patients, 40% have no income and approximately 45% have an income between 50 and 400 US dollars.

Approximately 35% of patients were the financial providers for more than 4 adult persons and at least 3 children in their household.


Fig 4: Monthly income of patients presenting for eligibility screening in the Initiative - Cd'Ivoire

A high percentage of patients had no professional activity. Approximately 31% of patients accessing the Initiative have been manual laborers, 26% salaried staff and 10% self employed (Fig 5).


Fig 5. Professional activity of patients accessing the Initiative as of March 31,2000 - Cd'Ivoire

1.2. Health status

1.2.1 Medical characteristics

Table 2 below shows the HIV serostatus, CD4 counts, and clinical status of patients accessing the UNAIDS/MOH Drug Access Initiative. Of all patients attending the eligibility screening, 90% were infected with HIV-1, more than 50% had a CD4 count of less than 200/µl, 55% met the 1993 CDC expanded AIDS case definition, and 35% were taking chemoprophylaxis for opportunistic infections, principally cotrimoxazole.

Table 2. Medical characteristics of patients presenting for eligibility screening in the Initiative - Cd'Ivoire (N=2144)

Characteristics

N

Percent

HIV status




HIV-1

1930

(90)


HIV-2

55

(3)


HIV-D

116

(5)




CD4 count (Fl)




0 - 199

1192

(55)


200 - 499

636

(30)


>500

314

(15)

CDC AIDS case definition

1178

(55)

OI prophylactic regimen

752

(35)

As shown in Table 3, few patients attending the eligibility screening had abnormal biochemistry values using the ACTG (AIDS Clinical Trial Group) classification scheme and a national evaluation scheme established by the School of Pharmacy of University of Cd'Ivoire. Very few abnormal values (grade 3 and 4) were recorded in the eligibility screening specimen of the three different categories of patients. Among ARV-na patients, drug-experienced patients receiving ARV, and drug-experienced patients not currently taking ARV, the prevalence of severe anemia was 8%, 3% and 5% respectively. Regarding the other biochemical parameters, fewer than 3% of patients in any group had abnormal values.

Table 3. Percentage of abnormal values in eligibility screening specimens of patients presenting for the Initiative

ACTG classification (grade 3 and/or 4)

ARV-na (n=1874)

Drug-experienced receiving ARV (n=222)

Drug-experienced not taking ARV (n=48)

Hemoglobin

8

3

5

Neutrophils

0

0

0

Platelets

1

1

0

Urea

0.5

0

2

Serum creatinine

1.5

0

3

SGOT

2

2

1

SGPT

0

0

0

Alkaline phosphatase

1

1

0

Amylase

0

0

0

Glycemia

0

0

0

1.2.2 Functional status

The major presenting symptoms were wasting, cough and fever. Figure 6 below shows the functional status of patients at the time of eligibility screening.


Fig 6. Functional status of patients presenting for eligibility screening in the Initiative - Cd'Ivoire

Although 72% were symptomatic, the majority had a normal activity.

1.2.3 Clinical signs and symptoms
Upon physical examination, the most frequent clinical findings were the following:

Leucoplakia

208 (10%)

Cachexia

227 (10%)

Polyadenopathy

461 (21%)

Dermatitis

496 (23%)

Candidiasis

971 (45%)

2- Assessment of non-prescription and prescription of ARV therapy

The second objective of this program evaluation is to identify reasons why some patients who presented for the eligibility evaluation did not receive ARV therapy. On Figure 7 is a flow chart with the status of na patients with or without follow-up and prescription of therapy.


Fig 7: ARV-naive patients acessing the UNAIDS/MOH Drug Access Initiative - Cote d'Ivoire, August 1998-March 2000

In this flow chart, 1874 na patients underwent the eligibility screening. Of these, 794 (40%) did not return to the clinics to obtain the results of the screening. An evaluation of the reasons for non-return to the clinics is planned for later this year. Patients will be contacted either by their care provider or social worker to document the reasons for non-return to the clinics.

Of the 1874 ARV-na patients presenting for initial screening, 1080 (60%) returned to the clinics for further evaluation. Of these, 422 received ARV therapy and 658 did not. At the initial screening, an additional 270 ARV drug- experienced patients have also presented. Of them, 48 had a history of ARV therapy but were not currently taking ARV drugs. These patients are not represented in Figure 7.

The reasons for non-prescription of ARV therapy among na patients who returned for further evaluation after initial screening have been the following:

Decision for subsidy pending

255 (39%)

Abnormal serum chemistry

217 (33%)

Serum chemistry to be rechecked

136 (21%)

Data missing

96 (14.%)

Viral load <4 log10 copies and/or CD4>500/µl

90 (14%)

The pending decision for subsidy accounts for the most important reason of non-prescription. As of March 31, 2000, 255 patients were still waiting to receive a decision on their application for subsidy. Of those, 86% have been awaiting the decision for more than 2 months (Figure 8).

Subsidy in the UNAIDS/MOH Drug Access Initiative is allocated by a National Committee and ranges from 50% to 95%. The table below compares characteristics of patients paying full price for their ARV drugs and those who obtained their drugs at a subsidized price.

Table 4. Characteristics of patients by subsidy category at initiation of therapy in the Initiative (n=649)

Characteristics

Paid full price

50% subsidy

75% subsidy

95 % subsidy

Income <$200

72

75

80

83

CDC AIDS case definition

62

52

54

50

CD4 count < 200/µl (baseline)

71

73

57

62

Viral load > 10,000 copies/ml

52

72

70

69

Patients who paid the full price were marginally less likely to have an income below US $200 compared with patients who received subsidies.

3. Follow-up of patients for whom ARVs are prescribed

As of March 31, 2000, 649 patients have been prescribed therapy through the UNAIDS Drug Access Initiative. Of these, 422 were ARV-na at the time of initial screening.

Based on an average enrollment rate of 32 patients per month, it is expected that 1152 patients would have started ARV therapy by August 2001.

3.1 Description of therapies prescribed
3.1.1 Medication classes of antiretroviral therapy available

Reverse transcriptase inhibitors (RTI)

-Nucleoside RTI (NRTI)
-Non Nucleoside RTI (NNRTI)

Protease inhibitors (PI)
Other adjuvants

-Hydroxyurea (HU)

3.1.2 Definitions

For the purpose of this evaluation, the following definitions will be used. Note that the following definitions are widely used and serve as the reference for antiretroviral therapy.

1- Highly Active Antiretroviral Therapy (HAART)

The intent of this type of therapy is to provide maximal suppression of plasma viral load. It includes:

· 2 NRTI+ NNRTI or
· 2 NRTI+ PI or
· 3 NRTI (if includes Abacavir)

2- 2NRTI usually referred to as "dual therapy"

The intent of this type of therapy is to suppress plasma viral load though the suppression may not be maximal. It includes:

· 2 NRTI+/- HU

3.1.3 Regimen prescribed

Figure 10 below is a pie charts presenting the regimen prescribed among na patients.

3.1.4 Characteristics of patients receiving ARV therapy


Fig 10: ARV regimens prescribed for naive patients

Na and drug-experienced patients beginning therapy under the initiative were compared regarding sociodemographic and clinical characteristics (see Table 5). Na patients were more likely to have a monthly income of less than US$ 200, lower CD4 counts at baseline, and were less likely to be on prophylaxis for opportunistic infection than drug-experienced patients.

Table 5. Comparison among characteristics of na and drug-experienced patients

Characteristics

Na (n=422)

Drug-experienced (n=222)

Mean age (years)

34

35

Female

41%

45%

Monthly income <US$ 200

68%

42%

Secondary education or lower

72%

69%

Median viral load at baseline (log10 copies/ml)

5.5

4.3

Median CD4 count at baseline (cells/µl)

89

192

Met CDC AIDS case definition

69%

33%

Taking OI prophylaxis

33%

45%

3.2 Evaluation of virological and immunological response to ARV therapy.

Patients enrolled in the UNAIDS Drug Access Initiative have been followed over time and evaluated biologically every 3 months. Patients have undergone biochemistry evaluation, CD4 count and viral load testing. Response for ARV-na patients will be the major focus in this chapter.

The assessment of virological and immunological response to ARV therapy response will be presented in the following fashion:

Therapy information was categorized as 2NRTIs, HAART and other. The analysis was conducted in two ways. Firstly, the response to therapy was assessed in an as-treated analysis and then in an intent to treat analysis. The latter is presented in the appendices 3 and 5. For both analyses, estimated response to antiretroviral therapy at selected times (days) after initiation of treatment was computed using the scatter plot smoother in S-PLUS software called "super smoother". This method was used to be able to assess response to therapy among patients who did not adhere to follow-up visits. This method uses regression splines to fit a continuous curve to the data by piecing together local fits to different portions of the data. The super smoother uses a cross-validation method to choose the span of data used for each fit. Laboratory measurements are assumed to be independent.

3.2.1. ARV-na patients
3.2.1.1. As treated

This type of analysis is based on the effective time patients have contributed to a specific type of therapy. Therefore, this analysis takes into account any change from one type of therapy to another.


Fig 13: Changes from baseline in viral load among ARV-naive patients (n=422) (As treated)


Fig 14: Percent of ARV-naive patients with undetectable viral load (n=422) (As treated)


Fig 16: Changes from baseline in CD4 count among ARV-naive patients (n=422) (As treated)

3.3 Clinical response to ARV therapy

3.3.1 Occurrence of opportunistic infections (OI)

In general, patients accessing the UNAIDS/MOH Drug Access Initiative were at an advanced stage of HIV infection upon accessing ARV therapy. This analysis presents the occurrence of opportunistic infections over time after initiating therapy. Figure 17 shows the time interval between initiation of therapy to the time patients present with the first symptom of the category B of the 1993 CDC expanded AIDS case definition. However, there are a number of limitations to this approach since it was neither possible to determine whether these patients had a previous history of AIDS nor to document it. Therefore, patients with an AIDS indicator disease at initiation of therapy were excluded and the clinical status used was based on the clinical examination on the day of initiation of therapy. At 6 months, 11% of patients had experienced at least one episode of opportunistic infection and this number increased to 18% at 1 year. This analysis did not reveal any difference in the different therapy groups. However, due to the limited number drug-experienced patients it was not possible to conduct this analysis by history of ARV therapy.


Fig 17: Time from initiation of therapy to the occurrence of the first opportunistic infection among patients without O1 at initiation of therapy (n=254)

3.3.2 Tolerance of ARV

At the eligibility screening, patients had a serum sample drawn for serum chemistry. The biochemistry evaluation is also performed on each patient at each follow-up visit. This chapter refers to adverse events for patients on ARV therapy. The severity grading is presented in the table below. At initiation of therapy, very few patients had abnormal biochemistry results as shown in the following table.

Table 6: Adverse events for patients on ARV therapy

Biochemistry

% with grade 3 or 4

Hemoglobin

4

Neutrophils

0

Platelets

1

Urea

0

Serum creatinine

0

SGOT

1

SGPT

0

Alkaline Phosphatase

1

Amylase

0

Glycemia

0

A Kaplan-Meier analysis was conducted to assess the time from the initiation of ARV therapy to the occurrence of the first adverse event (grade 3 or 4). Patients were censored at last visit or loss to follow up, and the analysis was restricted to persons with follow-up, laboratory values (more than 1 record per patient), excluding patients with adverse events at baseline. Approximately 18% of patients had an adverse event within 12 months.


Fig 19: Time from initiation of therapy to the occurrence of the first adverse event using ACTG classification scheme (n=454)

3.3.3 Adherence
Adherence to therapy in the UNAIDS Drug Access Initiative will be evaluated later this year.

3.3.4 Sustainability of therapy
Status of patients receiving therapy was determined as of March 31, 2000 and patients were classified into three major groups:

Patients active on ARV therapy:
patients who had an initial visit or a follow up visit in the 120 days prior to March 31, 2000, were considered active on ARV therapy.

Patients known to have died:
deaths are usually reported by a family member or next-of kin

Patients considered lost to follow-up:
if they did not have any visit in the 120 days prior to March 31, 2000.

The results among the 649 patients who were receiving therapy through the Drug Access Initiative are presented in the Figure 20 below. Patients who are known to be alive and who stopped ARV therapy as of last visit represent 2%. This number does not include patients who stopped and then resumed ARV therapy.

The probability of a patient staying in care, who is active taking ARV therapy was calculated by considering the patients who are known to have stopped ARV therapy or those who are lost to follow-up. This probability is 74% at 6 months and 62% at 12 months. Patients who had died were considered to have been actively on ARV therapy until their last visit and therefore were censored in this analysis.


Fig 20: Status of patients enrolled and receiving ARV therapy in the UNAIDS Drug Access Initiative as of March 31, 2000 -Cd'Ivoire

3.3.6 Causes of death

As of March 31, 2000, 44 patients were known to have died. There has been no possibility to document the causes of death. The deaths were usually reported by a family member or ascertained by a social worker when trying to invite patients who are late for their follow-up visit to return to the clinic. Therefore, there is possibility that the number of deaths reported may have been underestimated.

3.4 Survival

Analysis of survival was conducted and results were divided into two major components. The first analysis considers only patients known to have died. The outcome event in this type of analysis was the death. All the other categories of patients including those who stopped ARV therapy or were lost to follow-up during this period were considered to be alive up to the last visit.

3.4.1 Overall survival

The overall survival has been 93% at 6 months, 90% at 12 months, and 86% at 18 months. This effect is however not likely to reflect the reality because deaths are passively reported to the care providers by the family members.


Fig 21: Overall survival among patients receiving therapy (n=649)

3.4.2 Survival and remaining in care

The next survival curve presents a worse case scenario where patients who are lost to follow-up are considered to have died immediately after their last visit. This situation is more likely to depict the reality and to represent persons remaining in care in doctor's practice. In this curve, survival is 75% at 6 months and 64% at 12 months. The 18-month survival is approximately 55%.


Fig 22: Survival and remaining in care -UNAIDS Drug Access Initiative

4. Laboratory cost

Projet RETRO-CI has provided logistic and laboratory technical assistance in support of this initiative at its own expense during the 2-year pilot phase of this evaluation. Results have routinely been forwarded to the treating physician who decides whether to start ARV treatment. As set out in the original protocol, RETRO-CI support of this initiative has been intended for the purpose of evaluation and was not intended to be sustained beyond the period of the evaluation.

At the outset of this Initiative, UNAIDS negotiated reduced prices for certain ARVs through discussions with pharmaceutical companies. The price reductions have come in the form of subsidies from a special solidarity fund that was established by the Ivorian government and seeded with US$1 million. It has been hoped that this fund would be replenished by donations from corporations, donor agencies, as well as special taxes. Eligibility for these subsidies has been determined based on sociodemographic questionnaire data obtained by a social worker and reviewed by a national committee. However, another large part of the cost of sustaining ARV therapy is the costs of providing laboratory support, and the majority of these costs are the kits or diagnostic reagents themselves. As can be see in the Table below presenting the costs to Projet RETRO-CI of the various tests that are used in evaluations and in follow-up of each patient, the costs of reagents and diagnostic kits represent the majority of the laboratory costs.

Table 8: Projet RETRO-CI unit laboratory test costs

Test

Cost of test*

Salary

Over-head

Total

CBC

$3.57

$0.87

$2.66

$7.10

CD4

$23.10

$3.48

$10.65

$37.23

Multipanel

$8.48

$1.39

$4.26

$14.13

HIV-Elisa**

$3.38

$0.70

$2.13

$6.21

HIV-rapid**

$6.30

$1.74

$5.32

$13.36

Viral load

$52.50

$3.31

$10.14

$65.95

*reagents and/or kits; also includes disposables (5% of kit cost)
**two tests plus to confirm indeterminants

As set out in the Table 9 below, conservative calculations of the total costs of the evaluations at RETRO-CI from August 1998 through March 2000 exceeded US$630,000. This represents a cost of almost $300 for every patient presenting to the Initiative.

Table 9: Projet RETRO-CI costs of ARV Initiative activities (August 1998 - March 2000)

No. of Naive Patients

No. of Drug- Experienced Patients

Costs

Initial screening

1874

270

$192,699

Screening evaluation



Receiving treatment - initial

422


$ 57,256

Not receiving treatment but returning

658


$ 19,224

Follow up treatment visits





Units of 1 mo follow up

342

180

$ 76,659


Units of 4 mo follow up

329

173

$ 73,815


Units of 7 mo follow up

300

158

$ 67,199


Units of 10 mo follow up

295

155

$ 66,241


Units of 13 mo follow up

206

109

$ 46,369


Units of 16 mo follow up

145

75

$ 32,184

All evaluations


$ 631,646

Cost per patient presenting to Initiative


$ 295

Whereas UNAIDS has negotiated reduced prices for certain ARVs through discussions with pharmaceutical companies, similar negotiated price reductions for the cost of diagnostic kits and reagents has not yet been achieved. Based on the increasing numbers of patients being followed in this Initiative, consideration should be given to seeking ways of lowering these costs perhaps by working with the major marketers of diagnostic reagents and/or seeking alternative sources of support for future laboratory needs of this Initiative.

Summary

The results of this evaluation can be summarized in three sections related to the initiative procedures and their attendant laboratory costs:

Eligibility screening

· Over 20 months, 2144 patients have presented for the eligibility screening, with an average of 113 patients a month.
· 23% of patients were unemployed and 40% reported having no income.
· 75% were symptomatic: the majority had a normal activity
· 15% had CD4 count above 500 cells/
· Very few laboratory abnormal baseline values are reported

Initiation of therapy

· 42% of patients did not return for evaluation of their screening

· An average of 32 new patients are prescribed ARV therapy a month

· The main reason for non-prescription is the pending decision of the Committee regarding subsidy approval.

· Among na patients, 53% started therapy with a subsidy.

· At the time of enrollment in the Initiative, ARV-na patients have tended to have a lower CD4 count, have a higher baseline viral load, and have been more likely to meet the 1993 CDC expended case definition

· Overall 2 NRTI has been the most prescribed type of therapy, although recently HAART seems the preferred choice of regimen.

Follow-up

· After 20 months of therapy the status of follow-up is as follows: 2 % stopped, 7% died, 19% were lost to follow-up and 71% were active on therapy.

· Viral dynamics indicate that HAART has more promising results than 2NRTIs over time; however, so far there is no effect on morbidity, mortality.

· Very few severe adverse events in biochemistry values were reported.

Laboratory Costs

Projet RETRO-CI laboratory costs have been US $631,646 or almost $1,000 for each of the 644 patients treated in the Initiative. Most of these costs have been the costs of reagents and diagnostic kits.