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Research Article

# Cost-Effectiveness of Highly Active Antiretroviral Therapy in South Africa

Affiliation: Department of Medicine, Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa

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• Affiliation: Department of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa

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• Affiliations: NPMS-HHC Coordination and Analytic Centre, Chelsea and Westminster Hospital, London, United Kingdom, Department of Medicine, Imperial College, Chelsea and Westminster Hospital, London, United Kingdom

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• Affiliation: Department of Medicine, Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa

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• Affiliation: Division of Clinical Epidemiology, McGill University Health Centre, Montreal, Quebec, Canada

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• Affiliation: Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada

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• equal contributor Contributed equally to this work with: Robin Wood, Eduard J Beck

Affiliation: Department of Medicine, Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa

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• equal contributor Contributed equally to this work with: Robin Wood, Eduard J Beck

Affiliations: NPMS-HHC Coordination and Analytic Centre, Chelsea and Westminster Hospital, London, United Kingdom, Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada

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• Published: December 06, 2005
• DOI: 10.1371/journal.pmed.0030004

## Abstract

### Background

Little information exists on the impact of highly active antiretroviral therapy (HAART) on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices.

### Methods and Findings

Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3) and 27 with AIDS (WHO stage 4) receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group). Costs of service provision (January 2004 prices, US$1 = 7.6 Rand) included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of$730 per patient-year (PPY), whereas scenario 2 was based on the anticipated public-sector price for locally manufactured drug of $181 PPY. All analyses are presented in terms of patients without AIDS and patients with AIDS. For patients without AIDS, the mean number of inpatient days PPY was 1.08 (95% confidence interval [CI]: 0.97–1.19) for the HAART group versus 3.73 (95% CI: 3.55–3.97) for the No-ART group, and 8.71 (95% CI: 8.40–9.03) versus 4.35 (95% CI: 4.12–5.61), respectively, for mean number of outpatient visits PPY. Average service provision PPY was$950 for the No-ART group versus $1,342 and$793 PPY for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per life-year gained (LYG) was $1,622 for scenario 1 and$675 for scenario 2. For patients with AIDS, mean inpatients days PPY was 2.04 (95% CI: 1.63–2.52) for the HAART versus 15.36 (95% CI: 13.97–16.85) for the No-ART group. Mean outpatient visits PPY was 7.62 (95% CI: 6.81–8.49) compared with 6.60 (95% CI: 5.69–7.62) respectively. Average service provision PPY was $3,520 for the No-ART group versus$1,513 and $964 for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per LYG was cost saving for both scenarios. In a sensitivity analysis based on the lower (25%) and upper (75%) interquartile range survival percentiles, the incremental cost per LYG ranged from$1,557 to $1,772 for the group without AIDS and from cost saving to$111 for patients with AIDS.

### Conclusion

HAART is a cost-effective intervention in South Africa, and cost saving when HAART prices are further reduced. Our estimates, however, were based on direct costs, and as such the actual cost saving might have been underestimated if indirect costs were also included.

### Introduction

South Africa is experiencing an HIV epidemic with enormous social and economic consequences. Recent estimates suggest that between 4.5 and 6.2 million of the 43 million South Africans are infected with HIV-1 [1]. There were 370,000 AIDS deaths during 2003 [1], and the cumulative projected AIDS mortality for 2010 is 4–7 million in absence of a highly active antiretroviral therapy (HAART) programme [2]. The largest impact of HIV on the public health sector lies in the hospital sector [3]. In the year 2000, HIV-related admissions amounted to 24% of all public hospital admissions [4] and 12.5% of the total public health budget [5]. Cost of inpatient and ambulatory health care of both private and public health-care sectors is expected to rise rapidly [5].

#### Cost of LYG by WHO Stage of HIV Infection

Progression times were calculated from date of entry into non-AIDS (WHO stage 1, 2, or 3) to date of progression to AIDS (WHO stage 4) or death, and from initial diagnosis of AIDS (WHO stage 4) to death for AIDS patients. Patients not known to have progressed during follow-up were censored at either the most recent visit to the clinic or when lost to follow-up. Median progression times were estimated using the product-limit Kaplan-Meier survival method, and these were compared for the HAART and No-ART groups using log-rank test. Due to the small number of individuals who progressed during the follow-up period, median and interquartile ranges (IQR) for time to progression to AIDS or death were extrapolated from the product-limit time to failure estimates using the maximum likelihood least squares method. The progression-free times for non-AIDS and AIDS patients for each group were multiplied by the average PPY cost of service provision, and the additional life years gained of non-AIDS and AIDS groups was calculated as the incremental cost per LYG, based on the difference in the estimated median progression times of the two groups [27].

Because discounting health benefits remains controversial [35], only non-discounted estimates are presented. However, given the relatively short time in each WHO stage, it is unlikely that an analysis with a non-zero discount rate would yield qualitatively different results than those presented here.

#### Sensitivity Analysis

Robustness of results was assessed in a sensitivity analysis; accounting for variances associated with treatment effects and total cost of service provision. IQRs between the lower (25%) and upper (75%) progression-free times percentiles of the non-AIDS and AIDS patients were multiplied by the average and 95% CI of the cost of service provision, and the incremental cost per LYG was calculated.

### Results

#### Study Sample

Of the 1,630 patients in the cohort, 292 patients (265 non-AIDS and 27 with AIDS) received HAART through participation in the clinical trials. The rest of the patients (n = 1,328; 1,093 non-AIDS and 235 with AIDS) did not have access to ART during the study period and comprised the population from which the No-ART comparator group for the 292 patients who received HAART was identified. Baseline CD4 count, WHO stage, age, and socioeconomic status were independently associated with the likelihood of receiving HAART (Table 1), but gender was not, and therefore this variable was not considered in further analyses. Matching was therefore based on WHO stage, CD4 count (<200, 200–350, and >350 cells/μl), age (less than the median age or equal to the median age or greater of the non-AIDS and AIDS groups respectively) and socioeconomic status (low or high socioeconomic status).

HAART drug classes were not independently associated with increased risk of hospitalisation (Table 2) and were therefore analysed as one category. The characteristics of the final study population of the 292 patients who received HAART and the 292 matched No-ART patients are described in Table 3.

#### The Non-AIDS Population (WHO Stage 1, 2, or 3)

The matched non-AIDS group included 265 patients both in the HAART and No-ART group. Approximately one-third of the patients in the two groups had a baseline CD4 count <200 cell/μl and (49.4%) were of low socioeconomic status. Median age at inclusion into study did not differ in the two groups; 32 y, [IQR: 28–39 y] in the HAART group versus 32 y [IQR: 28–40 y] in the No-ART group (median test p = 0.48). Although not matched for, gender distribution did not differ statistically in the two groups (χ2 = 0.07, p = 0.79; Table 3). Median progression time was significantly longer in the HAART group compared with the No-ART group at 4.1 and 3.0 y respectively (log-rank test χ2 = 36.6, p < 0.001; Figure 1).

#### Use and Cost of Services and Cost per LYG

Patients on HAART had 1.08 (95% CI: 0.97–1.19) mean inpatient days, significantly fewer than the 3.75 d (95% CI: 3.55–3.97) of the No-ART group; χ2 = 147, OR = 0.29, 95% CI: 0.23–0.36, p < 0.001; but had significantly more outpatient visits of 8.71 (95% CI: 8.40–9.03) compared with 4.35 (95% CI: 4.12–5.61); χ2 = 145, OR = 2.00, 95% CI: 1.78–2.25, p < 0.0001 (Table 4). The average PPY inpatient cost in the HAART group was significantly less than that for the No-ART group, while the average costs of outpatient visits PPY for the No-ART group were less than those for the HAART group (Table 4).

Based on the two HAART price scenarios, the average cost of service provision PPY for the HAART group ranged from a minimum of $760 to$1,377 PPY, with scenario 2 having the lowest service provision cost (Table 4). The incremental cost per LYG for median progression time was $1,622 (95% CI: 1,607–1,627) for scenario 1 and$675 (95% CI: 659–679) for scenario 2 (Table 5). When a sensitivity analysis was performed based on the IQR of the progression times, the incremental cost per LYG varied between $1,578 (95% CI: 1,557–1,581) and$1,759 (95% CI: 1,748–1,772) for the 25th and 75th percentiles respectively (Table 5).

#### The AIDS Population (WHO Stage 4)

The AIDS population included 27 patients in each group. The majority of patients in the two groups presented with a CD4 count <200 cell/μl (77%), and 40.74% were of low socioeconomic status. Median age did not differ in the two groups; 35 y (IQR: 32–41) in the HAART group versus 37 y (IQR: 33–50) in the No-ART group (median test p = 0.27). Gender distribution, with 63% and 70.4% males in the HAART and No-ART groups respectively, was not significantly different in the two groups (χ2 = 0.33, p = 0.56) (see Table 3). Median progression time was significantly longer in the HAART group compared with the No-ART group; at 3.1 and 1.4 y respectively (log-rank χ2 = 5.28, p = 0.02; Figure 2).

#### Use and Cost of Services and Cost per LYG

Patients on HAART had significantly fewer mean PPY inpatient days at 2.04 d (95% CI: 1.63–2.52) compared with 15.36 d (95% CI: 13.97–16.85) for the No-ART group (χ2 = 1,019, OR = 0.13, 95 CI: 0.11–0.15, p < 0.0001). Mean outpatient visits PPY in the two groups did differ significantly; at 7.62 (95% CI: 6.81–8.49) for the HAART group compared with 6.60 (95% CI: 5.69–7.62) for the No-ART group; χ2 = 7.3, OR = 1.15, 95% CI: 1.04–1.28, p = 0.007, though not as substantially as for the non-AIDS group (see Table 4). The average inpatient cost PPY in the HAART group was significantly less than that for the No-ART group, but the average costs of outpatient visits PPY in the groups were not significantly (see Table 4).

### What Does This Mean?

HAART seems to be a more cost-effective way for South African hospitals to treat HIV infection than simply waiting for patients to come to hospital and then dealing with their symptoms. However, it should be noted that when a person is infected with HIV and becomes ill or dies from AIDS, it is not only hospitals that face costs. The patient, their family, and the country suffer financially. Effective treatment might also lower these “indirect” costs, but this was not an issue examined in this research.