Adopting Azidothymidine (AZT) Therapy For Treating HIV In Indigenous Population Of Australia: Critical Appraisal Of Research Articles

Literature search

Discuss about the Research Literacy for Health Practice.

Azidothymidine (AZT) or Zidovudine (ZDV) is an antiretroviral medication that is used for the treatment and prevention of AIDS/HIV. It helps in the treatment by reducing the viral replication that brings improvement in the blood tests and symptoms. It is also used in the prevention of transmission of HIV from the mother to the child. Although AZT slows the progression of AIDS in the patients by reducing the replication of HIV, it does not stop it completely (Kanters et al., 2016). The HIV becomes AZT-resistant with the progress of time and therefore, it is used in conjunction with the other medications of anti-HIV in the form of a combination therapy known as highly active antiretroviral therapy. The treatment of AIDS has undergone a drastic change in the past twenty years as the treatment options and knowledge has increased drastically. The combination therapy of antiretroviral medications delays the progression of AIDS but do possess substantial adverse effects and complications (Arts & Hazuda, 2012). WHO has laid down guidelines for the AZT therapy for delivering comprehensive HIV care in the public health approach. The guidelines are focused on maximizing the survival of the population by standardized sequencing of the therapy delivered by simplified approaches and is supported by basic laboratory and clinical monitoring (World Health Organization, 2013). This assignment is aimed at providing recommendations for the funding of a health intervention of adopting AZT therapy for the HIV treatment for the indigenous population of Australia through critical appraisal of research articles. The tools used for the purpose are CASP tool and the Onemda Critical Appraisal Tool for critically appraising the articles.

The literature search was carried out for the peer-reviewed journals and research articles on the topic of adopting AZT therapy for the treatment of HIV. The quality of the searched articles was determined by their ability to reflect on the research topic and the critical appraisal was compared with other similar articles to gain a broader knowledge on the research topic. Five academic databases were employed for the literature search that included Pubmed, EMBASE, CINAHL, PsycINFO and Cochrane Library. Only the empirical research papers that were published in English were selected for the study to recognize the international debate on the topic. The search period included for the study included recent articles from the last six years and the data collection tool for the inclusion and exclusion criteria was PRISMA tool. The search terms used for the study were Azidothymidine (AZT) therapy, HIV and indigenous population. The exclusion criteria included articles that were not within the study period, not focused on the research topic and not in English.

Antiretroviral treatment use

The first article used for the literature review was ‘Antiretroviral treatment use, co-morbidities and clinical outcomes among Aboriginal participants in the Australian HIV Observational Database (AHOD)’ by Templeton et al. (2015). The researchers provided a clear statement about the aims of the research and since there was a dearth of publications regarding the co-morbidities and clinical outcomes of the Indigenous Australians suffering from HIV, the authors carried out this study. The study described the use of antiretroviral medications like AZT among the HIV patients of the indigenous population of Australia and compared the outcomes with the non-indigenous participants with the consideration of the demographic factors. A prospective cohort study was carried out at 27 AHOD (Australian HIV Observation Database) sites that included sexual health clinics, general practice clinics and tertiary referral centers. The patients were selected in a non-random manner and it ruled out the chances of biases. Ethical approval was obtained from the human research ethics committee of Australia and the relevant review boards. Development of study procedures was done in accordance with the Helsinki Declaration. Although it did not include the ethical approval of the Aboriginal and Torres Strait Islander, the researchers had the written informed consent from the participating patients. Quantitative research design was employed for the study and it was appropriate as it gave an accurate outcome of the use of cART (combination Antiretroviral Therapy) with medications like AZT and the comparative results were appropriately derived. 3894 participants were recruited to the study by March 2013 and included 20 sites of AHOD.

The Indigenous status was present for 2197 participants. This recruitment strategy was appropriate to support the aims of the research as it aimed to study the use of the cART among the indigenous and non-indigenous populations. Data collection was carried prior to and during the research study. Clinical and demographic data were collected during enrolment and the various laboratory data were collected during the study to demonstrate the efficacy of the treatment. Data collection method was appropriate enough to address the research topic during the post-cART initiation for 24 months. However, in the study, the relationship between the participants and the researcher was not adequately considered. This was practically not possible considering the huge number of participants from both the indigenous and non-indigenous communities.

The data analysis was sufficiently rigorous considering the fact that descriptive statistics was employed for comparing the clinical information and patient demographics between the non-indigenous and indigenous AHOD participants. Apart from these, chi-square tests and t-tests were done for the categorical and continuous variables. This signifies the depth of the analysis carried out by the researchers for understanding the effect of the cART on both the types of participants. The statement of findings was stated in the discussion part and the clinical outcomes from the result were elaborated. Virological suppression was considered the most effective measure for the successful response to the applied cART. From the study, it was found that virological suppression was found in more than 80% of the participants who were treated with cART like AZT. This research was valuable for several reasons. This is because the study not only reflected good care engagement in care from its successful virological suppression, but also demonstrated the fact that there were very little or no differences in results between the indigenous and non-indigenous populations. This suggests that cART can be successfully utilized for the treatment of indigenous population of Australia suffering from HIV infections. However, the researchers have also pointed an important fact that adherence is the most important predictor that plays a crucial role in the virological suppression among the patients of HIV. Poor adherence can lead to reduce the durability of the regimen by causing drug resistance. These important findings from this study that has to be kept in consideration while designing the AZT therapy for the indigenous population in Australia.

Improving treatment outcomes

Another study was carried out by Dempsey et al. (2015) titled ‘Improving treatment outcomes for HIV-positive Aboriginal and Torres Strait Islander people at Cairns Sexual Health using the treatment cascade as a model’ and reflected on the activities of the multidisciplinary team of the health professionals of the Aboriginals and the Torres Strait Islanders for improving their treatment outcomes. The study had a clear statement of the aim of the research as it targeted to implement the treatment cascade as the model for gauging the success for the improvement of the outcomes of health of the indigenous patients suffering from HIV. The researchers focused on meeting adequately the client needs regarding service engagement, initiation, followed by adherence to ART (Antiretroviral Therapy). Qualitative methodology was used for carrying out this study as the intern pharmacists of the clinic carried out an audit by carrying out interviews of the indigenous HIV patients visiting the clinic. The interview process helped in getting clear idea of the engagement of the HIV patients with the ART like AZT or non-adherence of the patients with the therapy. The research design was appropriate to address the aim of the research since the study had limited number of cases and qualitative studies are the best possible method for providing the individual case information. The study included 25 patients from the clinic who were HIV positive and belonged to the indigenous community.

The recruitment strategy was appropriate for the study as it aimed at improving the treatment outcomes of the indigenous HIV patients and recruited the patients on the basis of the fact that 22 patients received ART, 20 engaged in cure and 16 cases were undetectable. Data collection was conducted for a period of 12 months and towards the end of the study, the study population rose to 29 patients with 27 males and 2 females. Data collection from the patient interview gave essential feedback from the patients that reflected on the facilitators and barriers of the treatment, especially with the use of the ART. Therefore, it addressed the research issue significantly as it helped to identify the treatment shortfalls and provided remedies for overcoming them. However, in the study, the relationship between the researcher and the participants has been considered as it helped them to conduct the interview and collect the data. Ethical approval was obtained from the ethics committee of Cairns Hospital and Health Services. The data analysis was sufficiently rigorous as it interpreted comparative results between the patients of the clinic and Australia wide prevalence of the factors like % engaged in care, % undetectable and % on ART. It also demonstrated the study progress over the time for the similar variables to represent the improvement in treatment outcome from the study. The statement of findings clearly stated that those patients who needed the maximum care for the treatment of HIV remained in ART for better outcomes. This makes the research valuable as it pointed out the fact that ART with AZT can be valuable in the treatment of HIV for the indigenous patients and adherence to the treatment is essential to improve the treatment outcomes.

Similar studies

To support the findings from both these studies, there are several other articles which demonstrated similar traits. Cohen et al. (2016) carried out a study titled ‘Antiretroviral therapy for the prevention of HIV-1 transmission’ where ART (with AZT) was offered to the patients who suffered from HIV-1 infection. The study assigned 1763 participants from nine countries where the couples were assigned randomly to two study groups. Statistical analysis was carried to analyze the study findings. From the recent reports, it is obvious that early initiation of the AZT therapy or ART can help to reduce the HIV-1 complications and preserve the immune function. From the study, it was found that apart from these advantages, ART helped to provide health benefits to the study participants on whom the treatment was applied. This study was important from the aspect that it gave a detailed account of the application of ART on the HIV patients on the patients of several countries of the world. ART was found to have public health benefits in the treatment of HIV. To provide momentum to the results of the study, univariate and multivariate analysis of the collected data was also carried out along with the baseline study. This in-depth analysis ensured the fact that ART can be successfully used for the treatment of HIV. Another opinion study was carried out by Laskey & Siliciano (2014) ‘A mechanistic theory to explain the efficacy of antiretroviral therapy’ for proposing a fundamental theory for explaining the mechanistic basis of the cART (with AZT). The study provided an in-depth knowledge of the cART and the theory of its efficacy with respect to the dose-response relationship. From the study, it has been found that the greatest obstacle is drug resistance for the treatment of HIV-1. The study have argued that the median effect model is the best fit method for the description of the dose-response relationship of the ART as the efficacy of ART gets reflected from the slope parameter. This study has been of importance for the fact that it not only provided the importance of ART in the treatment of HIV but it also focused on the resistance mutations which is of utmost importance for framing the treatment regime for HIV. Adherence to the treatment is important to prevent drug resistance with antiretroviral therapy. Broder (2010) conducted a similar study titled ‘The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic’ that is aimed at providing public health benefit with ART (with AZT). The researcher has extensively reviewed the studies since the era of the appearance of HIV-1 when it was considered untreatable. Since then, there have been significant changes in the treatment of the disease and ART is now no more limited to the resource-rich countries but also have it in the medical care of the resource poor countries. The researcher has also predicted the future of the treatment of HIV-1 with ART and has recommended that much research is required to transfer the knowledge from the laboratory to clinical practice for making the treatment more efficient without adverse effects. This article has also been important from the fact that it has focused not only on the treatment of HIV-1 but also considered the arenas of genetic diversity and viral drug resistance that are important from the perspectives of ART. Paradigm shifts has been proposed by the author against the host restriction factors and new viral targets or both of them that are essential while considering the treatment options with ART.

Considering the recommendations from all the articles that have been critically analyzed, a comparative study can be conducted. Templeton et al. recommended that adherence has been one of the most important and predominant factors for the treatment of HIV-1 and poor adherence can lead to the development of drug resistance and reduce the durability of the regimen for the indigenous Australians. A similar recommendation was put forward by Dempsey et al. who further added the fact that the indigenous people who have newly diagnosed with the disease should remain in care with ART. Consecutively, the studies by Cohen et al., Laskey & Siliciano and Broder had similar views on the treatment of HIV with AZT therapy and discussed the efficacy of the therapy in controlling the pandemic. The recommendations from these studies had a similar view that ART or AZT therapy is highly effective in the treatment of HIV among the indigenous population of Australia and precautions should be taken to continue the therapy without discontinuation.

An extensive literature search was carried out for establishing the efficacy of AZT therapy for the treatment of HIV and has been listed in Appendix – 1. AZT is recommended in combination with the other anti-HIV medications for the treatment of HIV but not for curing it. It has also been found effective in the prevention of the mother to child transmission of HIV during childbirth and pregnancy (Lenzi, Wiens & Pontarolo, 2015). Since monotherapy leads to the development of drug resistance, AZT should be used in combination therapy and it is absolutely safe for the fetus and the pregnant women. Arguably, it can be said that AZT has some severe adverse drug reactions like bone marrow toxicity, anemia, hepatic steatosis and lactic acidosis, it can be prevented by close monitoring of the patients if the symptoms start to appear (Creagh, 2013). Therefore, it is recommended for the government department to fund the health intervention of adopting AZT therapy for the treatment of HIV for the indigenous Australians and the health workers should take initiatives to initiate the intervention in the respective indigenous communities in Australia.

References

Arts, E. J., & Hazuda, D. J. (2012). HIV-1 antiretroviral drug therapy. Cold Spring Harbor perspectives in medicine, 2(4), a007161.

Broder, S. (2010). The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic. Antiviral research, 85(1), 1-18.

Cohen, M. S., Chen, Y. Q., McCauley, M., Gamble, T., Hosseinipour, M. C., Kumarasamy, N., … & Godbole, S. V. (2016). Antiretroviral therapy for the prevention of HIV-1 transmission. New England Journal of Medicine, 375(9), 830-839.

Creagh, T. H. (2013). We can illustrate an ambispective cohort study with our multicenter intensive postmarketing surveillance study which follows a group of patients with advanced human immunodeficiency virus (HIV) disease treated with zidovudine (RETROVIR8, AZT).] In late 1987, we began identifying every patient ever presenting with a diagnosis of HIV. Drug Epidemiology and Post-Marketing Surveillance, 224, 53.

Dempsey, M., Elliott, M., Gorton, C., Leamy, J., Yeganeh, S., & Scott, K. (2015). Improving treatment outcomes for HIV-positive Aboriginal and Torres Strait Islander people at Cairns Sexual Health using the treatment cascade as a model. HIV Australia, 13(3), 36.

Kanters, S., Vitoria, M., Doherty, M., Socias, M. E., Ford, N., Forrest, J. I., … & Mills, E. J. (2016). Comparative efficacy and safety of first-line antiretroviral therapy for the treatment of HIV infection: a systematic review and network meta-analysis. The Lancet HIV.

Laskey, S. B., & Siliciano, R. F. (2014). A mechanistic theory to explain the efficacy of antiretroviral therapy. Nature Reviews Microbiology, 12(11), 772-780.

Lenzi, L., Wiens, A., & Pontarolo, R. (2015). Comparison of antiretroviral schemes used in initial therapy for treatment of HIV/Aids. Acta Biomédica Brasiliensia, 4(1), 67-73.

Templeton, D. J., Wright, S. T., McManus, H., Lawrence, C., Russell, D. B., Law, M. G., & Petoumenos, K. (2015). Antiretroviral treatment use, co-morbidities and clinical outcomes among Aboriginal participants in the Australian HIV Observational Database (AHOD). BMC infectious diseases,15(1), 1.

World Health Organization. (2013). Global update on HIV treatment 2013: results, impact and opportunities.