Treatment of Human Immunodeficiency Virus with Zidovudine and Tenofovir Regimen in India: A Comparative Effectiveness Study.
Sowmyanarayanan, Thuppal.
2015
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Abstract: Human
Immunodeficiency Virus (HIV) is one of the leading causes of death among infectious
diseases. The adult HIV prevalence in India is around 0.27%. Combination anti-retroviral
therapy (ART) with tenofovir as a component is considered to be the most efficient drug
regimen along with emtricitabine and efavirenz. However in resource limited settings,
this combination is not preferred ... read moresince it is considered very expensive. Inspite of
higher rates of drug related toxicities zidovudine containing regimen with lamivudine
and nevirapine is considered the first-line treatment of choice in resource limited
settings, since they are less expensive. Comparative effectiveness studies from resource
sufficient settings show that tenofovir containing regimen is the better treatment for
HIV. But country specific studies are required to compare these two regimens and
identify the best treatment for that setting. Hence the objective of this PhD
dissertation is to compare the economic, clinical and quality of life outcomes in
patients living with HIV on treatment with zidovudine (along with lamivudine and
nevirapine) and tenofovir (emtricitabine and efavirenz) regimens from an infectious
disease clinic, at a private tertiary care hospital in southern India. To achieve this
objective we conducted four different projects: The first project documented the
toxicities and the cost of treatment for six months in patients living with HIV,
initiated on the current first-line zidovudine containing regimen. The study showed that
approximately 30% of the patients experienced drug related toxicity. Overall costs spent
on treatment for a period of six months excluding antiretroviral drugs (antiretroviral
drugs are provided free of costs to patients by the government) was Indian Rupees (INR)
7,157, which was one-third the average income earned by the patients during the study
period. Exploratory analysis comparing treatment costs, including both direct and
indirect costs showed that, patients with drug related toxicities had to spend
significantly more than patients without drug related toxicities, imposing an additional
significant economic burden to the patients. In the second project we compared the data
collected from patients initiated on both the regimens prior to implementation of the
government sponsored free antiretroviral therapy program. Patients who could afford to
pay opted for the expensive tenofovir containing regimen, while those who could not
afford opted for a less expensive zidovudine containing regimen. Since our study was
observational and ability to pay may have been associated with both selection of
treatment regimen and other characteristics potentially influencing health, we used
propensity score (PS) analysis to mitigate the potential confounding. Compared to
patients receiving zidovudine regimen, patients receiving tenofovir regimen had fewer
adverse drug reactions (47% vs. 11%, p-value: <0.01), requiring fewer regimen changes
(36% vs. 3%, p-value <0.01). With PS, zidovudine regimen had 8 times more adverse
drug reactions (p-value: <0.01). Opportunistic infections were similar between
regimens without PS, while zidovudine regimen had 1.2 times (p-value: 0.63) more
opportunistic infections with PS. Patients on tenofovir regimen gained more body mass
index. Increase in CD4 levels and treatment adherence (>95%) was similar across
regimens. Patients on a tenofovir regimen had better clinical outcomes with improved
general health than patients on zidovudine regimen. The third project was a pragmatic
randomized clinical trial comparing treatment naïve HIV positive patients started
on zidovudine and tenofovir containing regimens based on costs, clinical and quality of
life outcomes. Compared to patients on the zidovudine regimen patients on the tenofovir
regimen had significantly fewer adverse drug reactions (89% vs 45%, p-value: <0.01)
and required fewer regimen changes (35% vs 7%, p-value: <0.01). The proportion of
patients on zidovudine regimen experiencing opportunistic infections exceeded the
corresponding proportion for patients on the tenofovir regimen (46% vs 31%, p-value:
0.22). Patients on the tenofovir regimen tend to have better quality of life and
improved CD4 values than patients on the zidovudine regimen. Overall treatment costs did
not differ between the two regimens, however the cost of treatment in patients with
adverse drug reactions or opportunistic infections or both was greater in patients
receiving zidovudine regimen compared to those receiving tenofovir regimen. The study
findings suggest that compared to zidovudine regimen, the tenofovir regimen has fewer
adverse drug reactions and opportunistic infections with greater improvement in CD4
levels and quality of life. Fourth project was a cost effectiveness analysis between
zidovudine vs. tenofovir regimens. Model parameters including median costs, quality
adjusted life years from SF6D and EQ5D questionnaires, and transitional probabilities
were obtained from the pragmatic randomized study (project 3). A decision tree analysis
was performed to estimate the cost effectiveness for a period of one year. A Markov
decision model was performed for calculating the long term incremental costs and quality
adjusted life years. From payer perspective the tenofovir-containing regimen cost 8,091
Indian Rupees and conferred a health benefit of 0.02 QALYs compared to the
zidovudine-containing regimen, yielding a cost-effectiveness ratio of 404,550 INR (6,525
USD) per QALY. The Markov model projected an incremental cost of 1,768,298 INR (USD
28,521) and an incremental health gain of 0.08 QALYs. From the patient perspective, the
tenofovir-containing regimen reduced costs and improved health (decision tree analysis:
4,596 INR saved and 0.01 QALYs gained; Markov model: 44,413 INR saved and 0.08 QALYs
gained). Based on the WHO-CHOICE criteria for cost effectiveness analysis,
tenofovir-containing regimen was not cost effective with payer perspective, however was
cost effective with patient perspective. In conclusion, this PhD dissertation comparing
zidovudine and tenofovir containing regimens for HIV in India suggest that: Fewer
proportions of patients on the tenofovir regimen had adverse drug reactions and
opportunistic infections compared to zidovudine regimen. Cost of treatment due to
adverse drug reactions and opportunistic infections and the necessity for regimen change
due to adverse drug reactions were higher in patients receiving zidovudine regimen than
those patients receiving tenofovir regimen. From patient perspective
tenofovir-containing regimen saved costs and improved health in patient living with HIV.
Hence steps should be taken to reduce the procurement costs for the tenofovir-containing
regimen and to implement the tenofovir-containing regimen as the first-line treatment
regimen for patients living with HIV in
India.
Thesis (Ph.D.)--Tufts University, 2015.
Submitted to the Dept. of Clinical & Translational Science.
Advisor: Christine Wanke.
Committee: Joshua Cohen, Farzad Noubary, Mkaya Mwamburi, and Jayaprakash Muliyil.
Keywords: Public health, and Epidemiology.read less - ID:
- sf268h08d
- Component ID:
- tufts:20569
- To Cite:
- TARC Citation Guide EndNote
