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J Exp Clin Med 2012;4(4):239e244

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Journal of Experimental and Clinical Medicine

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ORIGINAL ARTICLE

Highly Active Antiretroviral Therapy Reduces Mortality and Morbidity in Patientswith AIDS in Sungai Buloh Hospital

Rozaini Mat Shah 1, Awang Bulgiba 2, Christopher K.C. Lee 3, Jamaiyah Haniff 4*, Mariana Mohamad Ali 4

1 Southern Seberang Perai District Health Office, Nibong Tebal, Seberang Perai Selatan, Pulau Pinang, Malaysia2 Julius Centre UM, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia3 Infectious Disease Unit, Department of Medicine, Sungai Buloh Hospital, Selangor, Malaysia4Clinical Research Centre, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia

a r t i c l e i n f o

Article history:Received: Mar 8, 2012Accepted: Mar 15, 2012

KEY WORDS:AIDS;AIDS-mortality rate;highly active antiretroviral therapy;human immunodeficiency virus;Malaysia

* Corresponding author. Jamaiyah Haniff, DermatLumpur, 50586 Jalan Pahang, Kuala Lumpur, Malaysia

E-mail: J. Haniff <jamaiyah@crc.gov.my>

1878-3317/$ e see front matter Copyright � 2012, Tahttp://dx.doi.org/10.1016/j.jecm.2012.06.011

Background: Highly active antiretroviral therapy (HAART) was introduced in Malaysia in 1997, but itseffectiveness has never been evaluated.Methods: This 12-year retrospective cohort study is the first attempt at evaluating the effectiveness ofHAART in Malaysia. Records from Infectious Diseases Clinic, Hospital Sungai Buloh, from 1997 to 2008,were matched with the National Registration Department Death Records 1997e2008 and Selangor StateHIV/AIDS/Death Surveillance database 1997e2008.Results: The median survival time was 134 (95% confidence interval: 97.93e170.07) months. Those onHAART lived significantly longer. The HAART group had a lower all-cause mortality rate (almost 30 timesfewer than those not on HAART,) and AIDS-defining events (at least 3 times less than those not onHAART).Conclusion: The mortality and morbidity of our patients were significantly lower with than withoutHAART. HAART should therefore be made accessible to all AIDS patients.

Copyright � 2012, Taipei Medical University. Published by Elsevier Taiwan LLC. All rights reserved.

1. Introduction

The discovery of antiretroviral therapy has been one of the mostdramatic advances in the history of medicine. The introduction ofthe first nucleoside reverse transcriptase inhibitor (NRTI), zidovu-dine, in the late 1980s marked the first therapeutic advances in thefield of human immunodeficiency virus (HIV) infection. This wassupported by randomized controlled trials (RCTs) documentingprolonged survival.1 Following this, later-licensed NRTIs, (didano-sine, zalcitabine and stavudine) for patients treated with zidovu-dine, and subsequent combination therapy of two NRTIs furtherdemonstrated their capacity to improve clinical prognosis.1

Another breakthrough was the discovery of a new drug class,protease inhibitors (PIs) targeting another point of HIV replication.Patients on PI therapy have a large turnover rate of HIV virions andinfected CD4-receptor-positive T lymphocyte cells (CD4 cells), aswell as a high mutation rate of HIV.2 RCT testing of such PI-containing combination therapy found improved survival rate, aswell as decreased HIV RNA and increased CD4 cell count; the latter

ology Block, Hospital Kuala.

ipei Medical University. Published

two being established predictive factors for clinical progression.3

Promising results in western trials led to the concept of highlyactive antiretroviral therapy (HAART), a regimen of two NRTIs anda PI or a non-nucleoside reverse transcriptase inhibitor (NNRTI),being introduced in Malaysia in 1997.

HAART has led to amarked reduction inmortality andmorbidityamong HIV-infected patients. This has been well documented inRCTs3,4 and later proven in large observational studies with long-term follow-up.5,6 However, most of these studies were from thewest. To the best of our knowledge, no such study has ever beencarried out in Malaysia, hence the present study was performed toestablish the efficacy of HAART in Malaysia.

Antiretroviral (ARV) agents entered Malaysia in stages; zido-vudinewas available in 1989 andwas followed in the early 1990s bydidanosine and zalcitabine. In the mid 1990s, stavudine and lam-ivudine were introduced.7 In 1997, HAART was introduced inMalaysia with the entry of the first PI, indinavir. Unfortunately,although HAARTwas technically available then, the prohibitive costprevented widespread use of these drugs.7

In 1996, the Ministry of Health ARV policy was to supportHAART through a “shared burden, shared responsibility” model.8

Only patients who fulfilled the selection criteria would be startedon HAART and provided one ARV agent for free. Selection criteriaincluded the ability to tolerate and complywith drug combinations,

by Elsevier Taiwan LLC. All rights reserved.

R. Mat Shah et al.240

comorbidity, stage of disease, and financial status (i.e., able topurchase the other two drugs by themselves).8 In June 2004, afterthe introduction of generic ARVs in Malaysia, the ARV policy wasthen upgraded to a two-drug subsidy policy.8

In Malaysia, HAART can be accessed through the medical clinicsof all general hospitals and some district hospitals (i.e., those withspecialist physicians).7 Some local university hospitals also provideARV treatment. All HIV clinics are run by specialist physicians, whohave had some training in HIV medicine, and are supported bynurse counselors, who have undergone attachments at the Infec-tious Diseases Clinic in Hospital Kuala Lumpur. The frequency ofthese clinics varies from once in 2 weeks to every day.7

To date, as far as we are aware, there has never been any localstudy of the effect of HAART in our setting. Against this backgroundof single (1997e2004) and two drug subsidy (2004 onwards)policy, we set out to study the effect (defined as death and AIDS-defining event) of HAART on HIV-infected patients under routineclinical care conditions in Hospital Sungai Buloh from 1997onwards. Local effectiveness evidencewould create local awarenessand later advocate changes in policy and clinical practice, so thateventually more patients can benefit from the usage of HAART.

In this study, we aimed to compare the median survival time,all-cause mortality rate in AIDS patients, and the incidence rate ofAIDS-defining events (ADEs) in two groups of patients (HAART vs.no HAART), and to identify the factors associated with clinicalprogression.

2. Methods

2.1. Study design

This was a hospital-based 12-year retrospective observationalcohort study of HIV/AIDS patients seen at the Infectious DiseaseClinic Hospital Sungai Buloh, Malaysia. As HAART has been provenelsewhere to be effective in treating HIV/AIDS patients, conductinga randomized, placebo-controlled trial is unethical. Thus, if oneintends to re-examine the effectiveness of HAART in a local context,the next best choice is the cohort study design. Hospital SungaiBuloh was chosen as the study site because it is the referral centerfor adult patients with HIV and AIDS for the West Central regionand is one of the major sites for HAART provision in Malaysia. Thissite is located in the state of Selangor. Selangor had the highest 3-year average of new HIV cases reported in the country followedby Kelantan and Johor in the years 2003, 2006 and 2009.9

We reviewed all case notes of patients attending the InfectiousDisease Clinic from 1997 to 2008. Inclusion criteria were: (1) adultsaged �18 years at the time of diagnosis with HIV; (2) HIV infectiondocumented by enzyme-linked immunosorbent assay and particleagglutination test; (3) AIDS defined as the presence of opportu-nistic illnesses or malignancies diagnostic of AIDS, and/or CD4 cellcount <200 cells/mL; or (4) individuals who met the US Centers forDisease Control and Prevention (CDC) definition.10 We excludedpatients who were: (1) infected perinatally; (2) �13 years of age atthe time of HIV diagnosis (because progression of HIV disease insuch individuals differs from that in adults)11; (3) hospitalized; or(4) receiving salvage therapy.

Study variables included demographic characteristics, HIV andAIDS diagnosis at any time during follow-up, CD4 cell count whenfirst diagnosed as AIDS, viral load when first diagnosed as AIDS,hemoglobin level when first diagnosed as AIDS, hepatitis B and Cstatus, ARV regimen initiated, and clinical outcomes. There werethree clinical outcomes of interest: (1) ADEs that were defined asdiagnosis of clinical category C conditions, based on the 1993 CDCclassification,10 and were measured by counting each new orrecurrent ADE as one event; (2) all-cause mortality; and (3) AIDS

survival time, which was defined as the time from first diagnosis ofAIDS to death.12 The patients records were matched with theNational Registration Department, Death Registration 1997e2008and the Selangor State Health Department HIV/AIDS/DeathSurveillance 1997e2008 databases to trace patients’ outcome event(death). Matching was done using names and National RegistrationIdentity Card number using exact and probabilistic matching soft-ware Quality Stage for the former and manual exact match for thelatter.

In 2006, antiretroviral drugs available in Malaysia were of threecategories namely NRTI, NNRTI and PI. The list of drugs are asfollows: NRTI [zidovudine (AZT), didonosine (ddI), zalcitabine(ddC), stavudine (d4T), lamiduvine (3TC) and AZT þ 3TC], NNRTI(efavirenz and nevirapine) and PI (indinavir, ritonavir, saquinavir,lopinavir and nelfinavir).13 Since February 2004, the three specificdrugs endorsed as “government use order” supplying all govern-ment hospitals are zidovudine, didanosine, and the combination oflamivudine zidovudine.9 For this study, patients were divided intotwo groups on the basis of whether they received HAART or not.The HAART group was defined as those who received at least threeARV drugs: two NRTIs and one PI or one NNRTI for at least 12months duration. The second group was those who did not receiveany HAART or received HAART for <12 months. The study protocolwas approved by the Medical Ethics Committee, University MalayaMedical Center, and the Medical Research and Ethical Committee,Ministry of Health, Malaysia.

2.2. Statistical analysis

Data analysis was carried out using PASW version 18.0. Descriptivestatistics were presented using frequencies with percentage andmean with standard deviation where appropriate. The univariateanalysis of demographic and clinical differences between the twogroups (survived or dead) was carried out using log-rank test(when the independent variables were categorical) and univariateCox regression (when the independent variables were numerical).This was followed with Cox proportional hazard regression to testthe independent variables simultaneously.

Survival time analysis was carried out to determine the riskfactors towards outcome. The survival time of the study wascomputed from the start date, defined as the date of diagnosis, anda common study end date at December 31, 2008. The AIDS survivaltime of both groups was assessed using the KaplaneMeier and Coxregression analysis. To compare the survival between those withHAART and non-HAART we applied the KaplaneMeier (log rank)test. The mortality incidence rate formula used is number of death/total number at risk * 1,000.

For continuous variables, univariate Cox proportional hazardregression, which is a semiparametric model, was used. Coxregression analysis was also used to determine important riskfactors towards outcome. Hazard ratio (HR) was defined as thechance of events occurring in the HAART group over the chance ofevents occurring in the non-HAART group. We considered p < 0.05as statistically significant.

3. Results

3.1. Description of sample

There were 2,444 HIV-infected patients being followed up at theSungai Buloh Infectious Disease Clinic during the study period. Atotal of 965 were dropped (901 because they did not fulfill theinclusion criteria and 64 because they met the exclusion criteria).Thus, the final analysis dataset consisted of 1,479 patients, of which592 were in the control group and 887 in the HAART group.

Table 2 Clinical characteristics of patients with advanced HIV-1 disease (AIDS and/or a CD4 cell count <200 cells/mL) by death status, independent of treat-ment, 1997e2008, Sungai Buloh Hospital

Variable Survived Dead Total

mean (SD) mean (SD) mean (SD)

HIV exposure categoryHomosexual 79 (7.0) 4 (1.3) 83 (5.8)Heterosexual 658 (58.1) 107 (34.9) 765 (53.1)IDU 235 (20.7) 131 (42.7) 366 (25.4)Heterosexual þ IDU 116 (10.2) 56 (18.2) 172 (11.9)Others 45 (4.0) 9 (2.9) 54 (3.8)

Ever had AIDS-defining eventNo 509 (43.9) 85 (26.6) 594 (40.2)Yes 650 (56.1) 235 (73.4) 885 (59.8)

HCV serology statusNegative 628 (66.6) 89 (33.6) 717 (59.4)Positive 315 (33.4) 176 (66.4) 491 (40.6)

HBV surface antigen statusNegative 923 (91.3) 231 (88.5) 1154 (90.7)Positive 88 (8.7) 30 (11.5) 118 (9.3)

CD4 cell count (cells/mL)�50 427 (36.8) 154 (48.1) 581 (39.3)51e200 594 (51.3) 110 (34.4) 704 (47.6)�200 138 (11.9) 56 (17.5) 194 (13.1)

Viral load(copies/mL)<10,000 198 (26.8) 13 (11.9) 211 (24.9)10,000e100,000 145 (19.6) 21 (19.3) 166 (19.6)>100,000 395 (53.5) 75 (68.8) 470 (55.5)

Hemoglobin concentration (g/dL) 12.42 (2.2) 11.36 (2.2) 12.20 (2.2)

ARV regimenNo ARV agent 329 (28.4) 264 (82.5) 592 (40.0)2 NRTIs þ 1 NNRTI 785 (67.7) 51 (15.9) 837 (56.6)2 NRTIs þ 1 PI 45 (3.9) 5 (1.6) 50 (3.4)

HAART statusNon-HAART 328 (28.3) 264 (82.5) 592 (40.0)HAART 831 (71.7) 56 (17.5) 887 (60.0)

All the predictors were significant at p < 0.05 except for HBV surface antigen status(p ¼ 0.141). ARV ¼ antiretroviral; HAART ¼ highly active antiretroviral therapy;HBV ¼ hepatitis B virus; HCV ¼ hepatitis C virus; IDU ¼ intravenous drug user;NNRTI ¼ non-nucleoside reverse transcriptase inhibitor; NRTI ¼ nucleoside reverse

Effectiveness of HAART in a Malaysian setting 241

The mean age of the study population at the time of diagnosis ofAIDSwas 38.27 (standard deviation 9.1) years old. The vast majorityof HIV cases were male (85.9%). There were more Chinese (51.9%)compared to other ethnic groups. The majority (78.1%) had attainedat least secondary education. Median monthly personal incomewas USD 95 (min USD 0, max USD 12,700). Most patients weresingle (56.1%). Eighty-three (5.8%) were probably infected via thehomosexual route; 765 (53.1%) were probably infected by theheterosexual route; 366 (25.4%) had a history of injecting drugs;and 172 (11.9%) had a history of both heterosexual contact andinjecting drug use. Positive hepatitis C virus serology status wasnoted in 40.6% but only 9.3% were positive for hepatitis B virussurface antigen.

The median CD4 cell count when AIDS was first diagnosed was81 cells/mL (range: 0e1,999 cells/mL). Meanwhile, the mediannumber of HIV RNA copies when AIDS was first diagnosed was138,000/mL (range: 0e2,618,890/mL). The mean hemoglobinconcentration when AIDS was first diagnosed was 12.12 g/dL. Themajority were on HAART (60.0%). Of the patients who were startedon HAART, 94.4% were put on the “two NRTIs þ one NNRTI”regimen, and only 5.6% were initiated with the “two NRTIs þ onePI” regimen. Demographic and clinical characteristics of the 1,479patients are summarized in Table 1.

Table 1 shows thatmortality was 82.5% (264/320 patients) in thenon-HAART group died at the end of the study compared to 17.5%(56/320 patients) in the HAARTgroup. However, apart fromHAART,death may also occur because of other predictors such as age, sex,ethnicity, income, marital status, exposure, ADE, viral load, and ARVregimen. To confirm whether HAART independently reducedmortality compared to non-HAART, we adjusted for confounders.The result is shown in Table 2.

3.2. Survival time and probabilities

The crude median survival duration of the non-HAART group was19 months [95% confidence interval (CI): 16e22 months]. Mean-while, there was no median survival duration for patients receivingHAART because the cumulative proportion surviving was still high

Table 1 Sociodemographic characteristics of patients with advanced HIV-1 disease(AIDS and/or a CD4 cell count <200 cells/mL) by death status, independentof treatment, 1997e2008, Sungai Buloh Hospital

Variable Survived Dead Total

mean (SD) mean (SD) mean (SD)

Mean age (yr) at diagnosis 38.03 (9.04) 39.16 (9.13) 38.27 (9.06)

Sex (n)Female 180 (15.5) 28 (08.8) 208 (14.1)Male 979 (84.5) 292 (91.3) 1271 (85.9)

Ethnic group (n)Malay 362 (31.2) 169 (52.8) 531 (35.9)Chinese 670 (57.8) 98 (30.6) 768 (51.9)Indian 109 (9.4) 49 (15.3) 158 (10.7)Others 18 (1.6) 4 (1.3) 22 (1.5)

Education status (n)Primary and less 79 (19.4) 40 (29.4) 119 (21.9)Secondary and above 329 (80.6) 96 (70.6) 425 (78.1)

Income group at diagnosis (n)RM 0e1000 646 (55.8) 249 (77.8) 895 (60.6)RM 1001e3000 294 (25.4) 33 (10.3) 327 (22.1)RM >3000 218(18.8) 38 (11.9) 256 (17.3)

Marital status (n)Single 630 (55.2) 185 (59.3) 815 (56.1)Married 427 (37.4) 78 (25.0) 505 (34.7)Divorced 71 (6.2) 44 (14.1) 115 (7.9)Widowed 14 (1.2) 5 (1.6) 19 (1.3)

transcriptase inhibitor; PI ¼ protease inhibitor.

(78.8 %) at study termination on December 31, 2008 (Figure 1).Three quarters (75%) of the patients on HAART were estimated tolive for up to 11 years. By contrast, for 75% of patients not on HAART,

Figure 1 KaplaneMeier estimates of survival probabilities of non-HAART and onHAART groups, 1997e2008, Sungai Buloh Hospital. HAART ¼ highly active anti-retroviral therapy.

Table 3 Comparison of 1-year, 3-year, 5-year and 10-year survival experience of patients with advanced HIV-1 disease, 1997e2008, Sungai Buloh Hospital by HAART status

Percent survival Survival estimation (yr) (SE) Cumulative survival proportion (%) X2 statistics (df) [p-value]

1 yr 3 yr 5 yr 10 yr

HAART 683.563 (1) [<0.001]75% 11.167 (29.153) 99.4 96.7 91.8 78.8*

50% d

25% d

Non-HAART75% 0.667 (0.744) 63.1 35.4 21.4 7.4y

50% 1.583 (1.404)25% 4.917 (4.872)

Overall 87.4 78.3 71.0 53.4

P value derived using log-rank test. df ¼ degrees of freedom; HAART ¼ highly active antiretroviral therapy; SE ¼ standard error.* Unable to get complete 10 years, followed up until 110 months only.y Unable to get complete 10 years, followed up until 114 months only.

Table 4 Factor associated with all-cause mortality for patients with advanced HIV-1disease, 1997e2008, Sungai Buloh Hospital

Variable Crude HR (95% CI) Adjusted HR (95% CI)

Age at AIDS diagnosis 1.02 (1.00e1.03) 1.03 (1.01e1.05)

CD4 cell count (cells/mL)�50 0.68 (0.50e0.93) 3.03 (1.06e8.69)51e200 0.39 (0.28e0.54) 1.42 (0.49e4.05)>200 1 1

Viral load (copies/mL)<10,000 1 110,000e100,000 2.31 (1.16e4.62) 2.00 (0.96e4.20)>100,000 3.13 (1.73e5.65) 2.46 (1.30e4.65)

Hemoglobin concentration (g/dL) 0.80 (0.76e0.84) 0.84 (0.76e0.93)

HAART statusNon-HAART 19.22 (14.31e25.82) 29.19 (18.59e45.86)HAART 1 1

CI¼ confidence interval; HAART¼ highly active antiretroviral therapy; HR¼ hazardratio.

R. Mat Shah et al.242

the estimated survival time was 8 months. This indicates thatpatients with HAART survived much longer compared to patientswithout HAART.

The 1-year, 3-year, 5-year and 10-year survival probabilitiesclearly showed the survival advantage for those on HAART(Table 3). The cumulative survival proportion decreased for bothHAART and non-HAART patients over the years. However, the ratewas more rapid in non-HAART patients; from 63.1% to 21.4% in 5years compared to the gradual reduction in patients with HAART,which was from 99.4% to 91.8%. This proved that patients withHAART have a higher survival probability. The actual 10-yearcumulative survival proportion could not be computed, thus, thenearest cumulative proportion was chosen. The Pearson c2 statis-tics had a significant difference (p < 0.05). This indicates that thetwo survival curves (HAART vs. non-HAART) differed significantly.The grouping variable (HAART or non-HAART) had a significantinfluence on the survival time.

3.3. All-cause mortality and ADEs

Themortality incidence rate for the non HAARTgroup was 30 timeshigher than the HAART group. The non-HAART group reportedmortality rate of 30.3 per 1,000 person-months whereas the HAARTgroup had 1.4 per 1,000 person-months. The overall incidence ofADEs was at least four times higher among the control group ascompared to those on HAART, with rates of 73.22 per 1,000personemonths and 17.62 per 1,000 personemonths observationsrespectively. Five leading ADEs were Mycobacterium tuberculosis(any site), Pneumocystis carinii pneumonia, cerebral toxoplasmosis,esophageal candidiasis, and cryptococcal meningitis.

3.4. Treatment (HAART vs non-HAART) towards outcome

In the univariate analysis, we identified several predictive factors.Men had an increased risk of death with HR of 1.99 (95% CI:1.36e2.94). When compared to the homosexual route, thoseinfected by injecting drug use (IDU), and heterosexual route withIDU, had increased mortality risk, with HR 9.27 (95% CI:3.43e25.08) and HR 7.50 (95% CI: 2.72e4.77), respectively. As forthe clinical characteristics: patients with higher viral load weremore likely to die compared to those with lower viral load. Usingthe lowest category, that is, those with viral load <10,000 copies/mL as the reference group, the hazard of death for those with viralload 10,000e100,000 copies/mL was higher (HR 2.31, 95% CI:1.16e4.62); and for those with viral load >100,000 copies/mL, HRincreased to 3.13 (95% CI: 1.73e5.65). Similarly, those not treatedwith HAART had a higher risk of dying, with HR 19.22 (95% CI:14.31e25.82), compared to those receiving HAART. In summary, all

the predictors were highly significant with HRs between 1.99 and19.22.

In the final model of multivariate analysis (Table 4), those withCD4 cell count <50 cells/mL and those with viral load >100,000copies/mL had a significantly increased potential risk of dying, withHR 3.03 (95% CI: 1.06e8.69) and HR 2.46 (95% CI: 1.30e4.65),respectively. Our final multivariate model confirmed that thosewho were in the non-HAART group had an increased potential riskof death almost 30 times higher HR 29.19, (95% CI: 18.59e45.86)than that in the non-HAART group.

4. Discussion

Advances in ARV therapy have changed the course of HIV infection.What used to be a disease with early morbidity and mortality isnow a chronic manageable disease. Benefits of HAART have beenreported in many western countries. HAART superiority was againproven in the present study in terms of a reduction in mortality andADEs. 6,14e16

The Ministry of Health Malaysia pledged support to the WorldHealth Organization’s “3 by 5” global campaign in 2003. The focuswas to be on issues related to access to treatment and care forpeople living with HIV/AIDS (PLWHA) in the country.17 This wasdone by improving the availability of treatment and lowering thecost, especially HAART. Since 2006, patients seen at governmenthospitals and clinics have had access to first-line therapiesinvolving NRTIs and NNRTIs at no charge.17 The average cost oftreatment per month per patient has dropped from RM 1,500 in2003 to RM 60e300 in 2007; representing up to 80e96%

Effectiveness of HAART in a Malaysian setting 243

reduction.18 The number of patients who are treated in governmenthospitals and clinics has also increased from 1,500 to 4,000.17 As ofDecember 2008, 8197 patients have benefitted from the policy.19

Under the government subsidy scheme, initially all patientswere given zidovudine. However, because of resistance and alsolowering the cost, more drugs were added (i.e., didanosine, zalci-tabine, stavudine and lamivudine). Later, to improve patientcompliance, the government decided to give combination therapy(single tablet). The dosage used during the period of study followedtheMalaysian Clinical Practice Guidelines in HIV/AIDS Treatment inMalaysia. However, despite the availability of ARV treatment atrelatively low cost, obstacles to access continue to exist.17 It issobering to note that out of an estimated 15,000 PLWHA whowould meet the criteria for treatment, less than 7,000 are currentlyreceiving ARV therapy.17

There are many reasons for this low uptake of treatment.20

These include low awareness among patients and health careworkers about (1) the benefits of HAART and (2) the reduction inthe cost of the medication.20 In addition, the number of HIV/AIDSservices centers in the country has also not expanded to keep upwith the growing epidemic.20 Thus, patients still need to travelsignificant distances to access these centers.17 In this country, HIVtransmission is mainly through sharing needles among drug users(75%).8,17 However, access to medical services among IDUs remainslimited.19 In the First Report of the National HIV/AIDS TreatmentRegistry 2003, the proportion of IDUs receiving HAART was only7%.7 Similarly, in this current study, the proportion of IDUs in theHAART group was small (12.8%) as compared to those not receivingHAART (44.5%). The IDUs are less likely to start on HAART becauseof: (1) financial constraints due to their addiction and inability togain and retain employment; (2) their poor compliance to follow-up appointments as a result of their chaotic lifestyle; and (3) thepoor family support often experienced by drug users.7,17

The Ministry of Health has undertaken initiatives to overcomethe issues mentioned earlier. Besides capacity development ofmedical officers at health clinics to manage ARV therapy, theMinistry of Health also has begun to provide ARV treatment withinthe setting of the Drug Rehabilitation Centers owned by theMinistry of Home Affairs.17 Our study has found that the survival ofpeople living with AIDS has improved significantly in thosereceiving HAART as compared to those not receiving HAART. Themedian survival of 19 months for the non-HAART group is consis-tent with previous studies in other parts of the world.21,22 Thisfinding should encourage policy makers to move forward to ach-ieve the “3 by 5” global campaign target. In conclusion, our studyhas established for the first time, in the Malaysian setting, howmuch HAART has made a difference in reducing morbidity andmortality in patients with HIV.

There were several strengths to this study. This is believed to bethe first report on survival of AIDS patients in Malaysia. Ourclinicians could use local data to convince patients about prog-nosis with regards to survival, with and without treatment. Themorbidity and mortality data obtained were of high quality, andused reliable official databases such as the National RegistrationDepartment Malaysia for deaths and the Selangor State HealthDepartment HIV/AIDS/Death surveillance database. Finally,having a large sample size such as in this study contributed to thepower of the study. The advantage of the retrospective cohortdesign was that all the events under study had already occurredand conclusions could therefore be drawn more rapidly. In addi-tion, the cost of the retrospective cohort study was substantiallylower for the same reason.

Limitations were unavoidable, especially those inherent to allretrospective studies using patient case notes. We faced issues suchas missing data (e.g., education status for 935 patients, and viral

load for 632). Another limitation was that we did not factor instaging of disease at enrollment, whichmay have caused bias in theassessment of progression to morbidity and mortality.

Not everyone who fulfils the requirement criteria for HAART inour present system has access to treatment due to its cost andadherence. Thus, with the evidence from one of our local hospitalsshowing a substantial advantage for those on HAART, more of thosewho need HAART should be given the opportunity. Further studiesusing more advanced survival analysis, such as recurrent eventsurvival analysis, as well as studies on barrier issues and ways toimprove access for the disadvantaged subgroups are highlyrecommended.

Acknowledgments

This study was supported by a grant from the PostgraduateResearch Fund, University of Malaya (P0022/2008A and P0027/2008C). We would like to express our gratitude to the DirectorGeneral of Health, Malaysia for permission to conduct this study inthe Ministry of Health.

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