Descriptive and retrospective investigation into clinical health outcomes of HIV patients on AZT-based regimens
Abstract
The number of people living with human immunodeficiency virus / acquired immune deficiency syndrome (HIV/AIDS) in South Africa keeps growing, those succumbing to the virus adding up to almost a third of all deaths in South Africa. This dissertation aimed to improve the clinical knowledge of zidovudine-based antiretroviral therapy (ART) and to contribute supportive evidence of the implementation of ART by different types of health care providers in different facilities in the City of Matlosana as part of Dr Kenneth Kaunda distrct in the North West province.
Antiretroviral therapy for the treatment of HIV is therefore a major priority for all health care systems worldwide. Initially, ART programmes in South Africa followed a physician-initiated and managed model. However, the limited number of physicians in the public sector forced a task-shifting approach from physicians to nurses to respond to the challenge to deliver ART programmes to a greater number of people. This led to the implementation of revised treatment guidelines, enabling nurse-initiated management of antiretroviral therapy (NIMART) in primary health care settings. Zidovudine (AZT), a nucleoside reverse transcriptase inhibitor, is widely used as part of second line regimens to treat HIV. Haematological disorders such as anaemia can occur within 4-12 weeks after AZT initiation and it mainly presents as macrocytosis but can also present as leukopenia or neutropenia. The monitoring of haematologic parameters is crucial for AZT-based regimens and full blood counts are currently advised at baseline, month 3, 6 and then 12 monthly thereafter.
HIV disease progression markers (CD4 cell counts & viral load (VL)), haematological markers (haemoglobin (Hb) & mean corpuscular volume (MCV)) and possible associated risk factors of disease progression (body mass index (BMI), hospital admissions & frequency of opportunistic infections(OIs)) were retrospectively extracted over a 12-month period from health records of adult patients on AZT-based treatment in a hospital clinic (n = 100) and NIMART cohort (n = 100) in the sub-district of City of Matlosana, North West province, in order to compare these two approaches. Other primary health outcomes variables such as time to undetectable VL suppression, time from enrolment to death, time since HIV diagnosis, total time spent on ART and AZT were also included. One hospital clinic, two primary health care clinics and one community health centre clinic were included. Ethics approval was obtained from the Human Research Ethics Committee (HREC), North-West University (NW-00362-15-A1), Wits HREC medical (M160267), PPRM&E directorate (North West Department of Health), the CEO of Tshepong-Klerksdorp hospital complex and the acting PHC manager. Descriptive statistics were used to present the demographic results of the two cohorts. Linear mixed models which adjusted for age, total duration on ART and duration since HIV diagnosis were incorporated to analyse disease progression marker (CD4 cell count), haematological parameters (Hb & MCV) and BMI as an associated risk factor for disease progression. Kaplan-Meier survival analysis was used to determine the effect of time on undetectable VL suppression in both cohorts over time.
The mean (SD) age for hospital, clinic and NIMART patients was 42.4 (± 8.92) and 50.30 (± 1.82) years respectively, with females comprising the biggest proportion of patients in both cohorts (59% and 69% respectively). Both OIs and hospital admissions occurred more frequently for the hospital clinic cohort.
After adjusting for the three confounding covariates, CD4 cell count increased significantly overall in both cohorts, but indicated no significant differences (p > 0.05) over time (p = 0.562, 𝐹 = 0.582), between the cohorts (p = 0.091, 𝐹 = 2.899) or for the time*cohort interaction (p=0.927, 𝐹 = 0.076). Haemoglobin for both groups also reacted similarly and relatively unchanged over time with no interaction (time*cohort; p = 0.835, 𝐹 = 0.180) to report, thus not achieving anaemic status (< 8 g/dL) after 12 months on AZT-based regimen. The MCV, however, increased significantly over time (p = 0.009, 𝐹 = 5.255), more specifically between baseline and month 12 (p = 0.008), but showed no statistical differences between the cohorts (p = 0.227, 𝐹 = 1.476) or indicated an interaction between time*cohort (p = 0.128, 𝐹 = 2.152). Macrocytosis was already evident in the NIMART group at baseline and continued up to 12 months compared to being present only at 6 and 12 months in the hospital clinic cohort. Macrocytic anaemia (macrocytosis and Hb < 8 g/dL) was only observed in 1% (one in each cohort) of the study population. Body mass index values were almost unchanged over the first year on AZT-based therapy for both cohorts and did not differ significantly between the two cohorts.
In total, 58% of all patients (both cohorts) achieved successful viral suppression, although NIMART patients (80%) were considerably more successful in achieving VL suppression compared to the hospital clinic patients (36%) possibly due to the median baseline VL already < 20 copies/ml in 44% of the NIMART cohort. It is important to emphasise that although the two survival curves were not equivalent they followed the same trend for both cohorts at 6 and 12 months of analysis. The estimate mean time for NIMART subjects to have reached VL suppression (5.7 ± 5.4 months) were almost twice as fast compared to hospital clinic subjects (10.4 ± 3.6 months).
Both cohorts showed improved clinical treatment outcomes with significantly elevated CD4 cell counts and viral suppression 12 months after AZT-based initiation. The parameters (CD4, Hb, MCV, BMI) measured were similar between the two cohorts over the 12-month period however the NIMART cohort reached VL suppression quicker compared to the hospital clinic cohort possibly due to better VL suppression at baseline. Based on these results we conclude that NIMART was non-inferior to physician-managed ART in this study setting. There is a need for more comparative research studies where these approaches can be measured and investigated. Considering the most recent change in HIV treatment guidelines, enabling the initiation of all HIV positive patients on ART irrespective of their CD4 cell count and considering the immense burden this places on the public health care systems and human resources, this study contributed to the existing knowledge of implementing NIMART especially where second line regimens are concerned
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