Outcomes of antiretroviral therapy in a northern Indian urban clinic

Abstract

Problem

Antiretroviral therapy (ART) programmes have been successful in several countries. However, whether they would succeed as part of a national programme in a resource-constrained setting such as India is not clear. The outcomes and specific problems encountered in such a setting have not been adequately studied.

Approach

We assessed the efficacy and functioning of India’s national ART programme in a tertiary care centre in northern India. All ART-naive patients started on ART between May 2005 and October 2006 were included in the study and were followed until 31 April 2008. Periodic clinical and laboratory evaluations were carried out in accordance with national guidelines. Changes in CD4+ lymphocyte count, body weight and body mass index were assessed at follow-up, and the operational problems analysed.

Local setting

The setting was a tertiary care centre in northern India with a mixed population of patients, mostly of low socioeconomic status. The centre is reasonably well resourced but faces constraints in health-care delivery, such as lack of adequate human resources and a high patient load.

Relevant changes

The response to ART in the cohort studied was comparable to that reported from other countries. However, the programme had a high attrition rate, possibly due to patient-related factors and operational constraints.

Lessons learnt

A high rate of attrition can affect the overall efficacy and functioning of an ART programme. Addressing the issues causing attrition might improve patient outcomes in India and in other resource-constrained countries.

Introduction

The number of people infected with the human immunodeficiency virus (HIV) worldwide was estimated to be 33.2 million at the end of 2007.¹ The introduction of antiretroviral therapy (ART) has significantly reduced morbidity and mortality in HIV-infected patients in various developed and developing countries.^2–5 However, the outcome of ART in India’s national ART programme has not been reported.

Background

India is a developing nation with approximately 2.4 million people living with HIV and a national prevalence of HIV infection in adults of 0.36%.¹ Until 2004, ART was available only to a select subset of patients through the private sector; most of the HIV-infected population was unable to afford ART. India’s national ART programme was launched on 1 April 2004 under the National AIDS Control Organisation (NACO), as an initiative of the Ministry of Health and Family Welfare of the Government of India. The programme was launched in eight institutions in six states with a high prevalence of HIV infection, and in the National Capital Region of Delhi. By December 2008, 197 ART centres were functioning in 31 states and union territories and more than 193 000 patients were accessing free ART through these centres.⁶

Setting

To ascertain the functioning and efficacy of the national ART programme, we assessed an ART centre that was opened at the All India Institute of Medical Sciences (AIIMS) Hospital, New Delhi, in May 2005.

The AIIMS Hospital provides tertiary care to the population of Delhi and its neighbouring states, and most of its patients come from the lower socioeconomic strata. Patients with HIV infection tend to present in advanced stages of acquired immunodeficiency syndrome (AIDS) and are usually referred to the hospital’s ART centre, which is staffed by a nodal officer, two physicians, a laboratory technician, a pharmacist, a nurse (who also acts as an AIDS educator), an ART counsellor, a data manager and a community health worker. The centre receives financial and logistic support from NACO through the Delhi State AIDS Control Society.

This paper reports the outcomes of ART delivered from the clinic at the AIIMS Hospital and highlights some of the problems encountered in implementing ART.

Methods

To evaluate the effectiveness of the national ART programme at the AIIMS Hospital, we undertook a prospective observational study involving ART-naive patients who were started on ART between May 2005 and October 2006. ART was offered to these patients in accordance with NACO guidelines.⁷ The regimen consisted of two nucleoside reverse transcriptase inhibitors and one non-nucleoside reverse transcriptase inhibitor. The available drugs included efavirenz, lamivudine, nevirapine and zidovudine. The medications were dispensed directly to the patients or their authorized representatives.

Patients were seen 2 weeks after the start of ART and thereafter on a monthly basis. During each visit, patients were evaluated for drug toxicity, clinical improvement and opportunistic infections. Adherence was assessed during each visit by pill count, and, through counselling, patients were motivated to adhere to therapy. Patients who failed to turn up within a week of the scheduled visit were contacted by telephone. The CD4+ lymphocyte (CD4) count (cells/µl) was estimated at baseline and at 6-month intervals during follow-up. Prophylaxis and treatment of opportunistic infections were in accordance with NACO guidelines. Anti-tuberculosis treatment was administered according to the Revised National Tuberculosis Control Programme guidelines.⁸

Results

Between 1 May 2005 and 31 October 2006, 1325 patients were enrolled in the ART clinic. Of these patients, 631 treatment-naive adolescents and adults were eligible for the study. Baseline characteristics for those enrolled in the study are provided in Table 1. Patients had a mean age of 36 years (standard deviation, SD: 8.69); a mean weight of 54 kg in males (SD: ±10.03) and of 44 kg in females (SD: ±8.68); a mean body mass index of 19.25 kg/m² (SD: ±3.19); a mean haemoglobin of 11 g/dl (SD: ±2.38) and a median CD4 count of 110 (interquartile range: 59–159). All patients were followed until 31 April 2008; the median follow-up period was 21 months (range: 0–36 months). At the end of 36 months, 344 of the 631 patients (55%) were still being followed; 139 (22%) had been lost to follow-up, 77 (12%) had died and 71 (11%) had been transferred to other NACO-sponsored ART centres. Among those lost to follow-up, 60% were lost during the first 3 months and 84% by one year.

Table 1. Baseline characteristics of patients in a study of antiretroviral therapy outcomes in a tertiary care centre in northern India, 2005–2006.

Characteristic	Value					Characteristic	Value
	No.		%				No.		%
Total study population (n = 631)						Occupation
Malesa	502		80			Unemployed	218		34
Females	129		20			Unskilled worker	131		21
Age (years)						Semi-skilled worker	104		17
15–20	8		1			Skilled worker	52		8
21–30	187		30			Clerk/shop owner/farm owner	93		15
31–40	297		47			Semiprofessional	14		2
41–50	99		16			Professional	19		3
> 50	40		6			Mode of transmission
Malnourishedb	219		44			Blood transfusion	37		6
Education						Heterosexual	542		86
Illiterate	113		18			Homosexual	5		1
Primary school	132		21			Professional needlestick	1		0.2
Middle school	87		14			Surgical	2		0.3
High school	120		19			Unknown	27		4
Intermediate schoolc	78		12			Unsafe injection	12		2
Bachelor’s degree	78		12			WHO clinical stagee
Professional/post-graduate degree	23		4			1	84		13
Monthly income (Indian rupees)d						2	33		5
< 40	4		1			3	320		51
40–119	9		1			4	194		31
120–199	17		3			Anaemiaf
200–299	52		8			Male	296		77
300–399	97		15			Female	91		82
400–799	224		36			TB at the start of ART	177		28
≥ 800	228		36			Initial ART regimen
Smoker	63		10			Stavudine + lamivudine + nevirapine	312		49
Alcohol consumer	22		4			Stavudine + lamivudine + efavirenz	99		16
						Zidovudine + lamivudine + nevirapine	153		24
						Zidovudine + lamivudine + efavirenz	67		11

ART, antiretroviral therapy; TB, tuberculosis; WHO, World Health Organization.
^a The national data show a male to female ratio among the HIV-infected population of 61:39.^9
b Malnutrition was defined by a body mass index (BMI) (kg/m²) < 18.5.
^c Intermediate school refers to the two years of education after high school in the 10 + 2 pattern of school education.
^d One United States dollar was equivalent to about 47 Indian rupees in May 2009.
^e Stages 3 and 4 are advanced stages of HIV infection.
^f For males, blood haemoglobin < 13 g/dl; for females, < 12 g/dl.

There was a consistent increase in the median CD4 count over the study period (Fig. 1). The CD4 count at 6 months was greater than the baseline value in 421 of 440 patients (96%). In total, 61% of patients gained weight, from a median of 50 kg at baseline to 57.5 kg at 36 months. Similarly, body mass index increased from a median of 19.2 at baseline to 21.6 at 36 months.

Fig. 1.

Changes in median CD4+ lymphocyte count over 36 months in a study of antiretroviral therapy outcomes in a tertiary care centre in northern India, 2005–2006

Survival analysis showed that 90% of the patients were alive at 6 months, 87% at 12 months and 84% at the end of 36 months. The overall mortality rate was 8.5 per 100 patient–years and the post-90-day mortality rate was 5.8 per 100 patient–years. There was no significant difference in survival between patients with and without tuberculosis (TB) (P = 0.623). A total of 192 patients (30%) required a change in their first-line medication. The most common reasons for this were initiation of anti-tuberculosis treatment (127 patients, 66%), adverse drug reactions (57 patients, 30%) and treatment failure (8 patients, 4%).

Discussion

This study confirms that ART delivery through a national programme in a resource-constrained setting can be effective. Most of the patients in the study showed a good clinical response to therapy, as indicated by significant weight gain and improvement in CD4 count. Around 82% of them had reached an advanced stage of illness (World Health Organization stage 3 or 4) at presentation, highlighting the need for early diagnosis and treatment. The overall mortality rate in our study was higher than reported from other developed and developing countries.^10,11 Nevertheless, the post-90-day mortality rate was similar to the rate observed in another study.¹⁰

In line with previous studies, we found no significant association between TB and mortality.^5,12 In a study from Uganda, TB was associated with increased mortality only in HIV patients with a CD4 count > 200 cells/µl.¹² It may be that TB facilitates HIV viral replication to a greater extent in the earlier stages of HIV infection than during advanced illness, when viral replication is already at its peak. In our study, patients with TB had a mean baseline CD4 count of 109 cells/µl, indicative of advanced disease; this may explain why TB was not significantly associated with mortality. In addition, treatment for TB was rigorously supervised under the directly observed treatment strategy of the Revised National Tuberculosis Control Programme.

A major limitation of this study is that the causes of mortality were unknown; most deaths occurred at home and their exact causes could not be ascertained by telephone. Another limitation was the high number of patients lost to follow-up. This group requires special attention because it tends to have higher mortality, as shown in a recent review.¹³ The high loss to follow-up may have been linked to poverty (all patients had a monthly income of < 17 United States dollars), unemployment (34%) and a poor literacy rate (53% patients had not completed high school), coupled with poor awareness of AIDS and social stigma about the disease, as revealed by a similar study from India.¹⁴ Other deterrents to patient follow-up may have included initial improvement in health, adverse drug reactions and difficulties with transport (most patients came from distant areas with poor transport facilities). Currently, the only mechanism in the programme for retrieving patients lost to a treatment facility is to telephone them – an approach that is inadequate because of poor patient response or incorrect or outdated telephone numbers. Loss to follow-up during transfer of patients to other health-care facilities was another weak area in patient care.

The setting we studied had reasonable resources and was favourably located in an urban area. Nevertheless, we encountered difficulties such as limited human resources for handling the high patient load; lack of adequate space in the clinic for counselling, examination and investigations; difficulty in maintaining confidentiality due to lack of separate rooms; and lack of availability of second-line ART.

Potential solutions to the issues raised here include better education and motivation of patients, early referral for diagnosis and treatment, decentralization of the ART programme, institution of home visits, an increase in human resources and provision of adequate space in clinics, and greater availability of second-line ART for non-responders. Creating social support groups and a vibrant patient education programme, not only in the hospital but also in the communities near patients’ residences, would help dispel the misconceptions and stigma associated with HIV infection. Decentralizing the programme and providing travel reimbursement would undoubtedly increase attendance, and strengthening communication among local ART centres would enhance continuity in patient care. And while greater involvement on the part of nongovernmental organizations in HIV care and treatment would obviously be beneficial, it requires good audit and accountability systems to prevent the misuse of resources.

We feel that better treatment outcomes would be achieved by strengthening human resources in the centre, improving the infrastructure, diverting stable patients to peripheral ART centres and providing second-line ART for non-responders. Prioritizing sick HIV-infected patients for hospitalization may also lead to improved outcomes.

Box 1 summarizes the lessons learnt in this study.

Box 1. Summary of main lessons learnt.

• Treatment outcomes observed in our study are comparable to those reported in previous studies in other settings and show that antiretroviral therapy (ART) delivery through a national programme in a resource-constrained setting can be effective.

• A high attrition rate can affect the overall efficacy and functioning of an ART programme.

• Addressing the issues causing attrition may improve patient outcomes in India and in countries with similar resource-constrained settings.

Conclusion

The treatment outcomes observed in our study are comparable to those reported in previous studies. Although the results are based on a limited number of patients and arriving at definitive conclusions may be premature, the results draw attention to certain important constraints that an ART centre would face in the Indian subcontinent. Such sociocultural and operational constraints need to be properly addressed, besides provision of free ART, to derive the complete benefit of ART through such a national programme. ■