Human immunodeficiency virus (HIV) destroys CD4 cell numbers, raises HIV RNA plasma levels, and causes long-term acquired immunodeficiency syndrome (AIDS) [1], [2]. Worldwide, 37.7 million (30.2–45.1 million) people lived with HIV in 2020, of which 28.2 million were receiving antiretroviral therapy as of June 30, 2021). Of the total of 37.7 million people living with HIV, the majority come from low- and middle-income countries, and sub-Saharan Africa accounts for two-thirds (67%) of people living with HIV [3], but only about 12% of the world's population [2].
The CD4 + count is used as assessing the clinical status of HIV-infected patients in making decisions regarding the initiation of antiretroviral therapy (ART) [4]. Measuring CD4 + count is a strong predictor of progression to Human Immunodeficiency Syndrome (AIDS) as well as a means of monitoring the success of such antiretroviral therapy [5]. The possible increase or decrease in CD4 + counts are directly related to HIV replication. Low CD4 + counts are associated with a greater risk of patients living with HIV developing opportunistic infections, which may then progress to advanced disease and death [4], [5]. In a healthy adult, a normal CD4 + count can vary enormously (by population, age group, etc.), but is typically around 500 to 1500 cells per cubic milliliter of blood (mm3) [6]. When it falls below 200, however, then the disease is technically classified as AIDS.
In ART-stable patients, CD4 cell counts are not required to monitor treatment response when HIV viral load tests are available [7]. However, CD4 remains the best measure of a patient's immune and clinical status, risk of opportunistic infections, and supports diagnostic decision-making, especially in patients with advanced HIV disease[7]. Moreover, the use of combinations of antiretroviral drugs (ART) greatly results in the supervision of virus replication and hence increased levels of CD4 + count. The CD4 + count is also used to decide when to start antiretroviral therapy. Initiation of Highly Active Antiretroviral Therapy (HAART) at higher CD4 + counts has been demonstrated to “the risk of death, opportunistic infections, and non-HIV related comorbidities”[8]. Combined with at least two to three types of antiretroviral therapy, HAART effectively lowers the levels of the virus in the body by increasing the immune system's known CD4 + count.
More previously, limited studies were focused on modeling the CD4 + counts trend over time for patients on ART [2]. However, [9] suggested that the progression of CD4 + T-cells follows a pattern of a long periods of slow decline followed by a rapid decline just before the onset of AIDS. Here, it indicates the need further investigation for the question what happens about the progression after the start of HAART.
In a previous study, HAART brought a significance improvement on CD4 + count and provided further quantitative evidence about aspects of the therapy effect such as the changes in the slope of CD4 + cell count [10]. Moreover, patients who had already experienced an AIDS defining event at the point of initiating HAART were also at higher risk of developing a new event, irrespective of their CD4 + count evolution during treatment [11].
In the previous studies, predictors such as baseline CD4 cell count [12]–[21], follow-up time [12], [14], [16], [18], [21]–[23], regimen d4t-3TC-NVP and AZT-3TC-NVP,[12], initial regimen of AZT + 3TC + EFV[20], but all ART regimens without significance difference that increased mean CD4 count at the study period [13], functional status [17], [22], working functional status [13], [18], [19], baseline age [14], [16], [17], [22], [23], younger age [13], [18], baseline WHO stage [17], [19], [21], [22], baseline WHO clinical stage II [20], [24], marital status [14], [16], [17], sex of patients [16], [21], [23], patients’ level of education [16], tertiary level of education [20] were identified as significant factors that significantly contribute to the changes of patients CD4 cell count.
Even when HIV-infected patients are advised to initiate ART, assessing the improvement in CD4 + counts over time after the patient initiates HAART, and whether the pattern of therapy varies depending on the patient’s characteristics such as gender, age, functional status, and dietary intake, etc. is very crucial. Moreover, since the data is measured on the same subject, repeatedly, taking this correlated data as independent leads to inappropriately estimated standard errors and inefficient estimators. Hence, using linear mixed models is also important to incorporate the random effects of between-subjects variability. This study therefore aimed to examine the progression of CD4 + counts over time and to evaluate the determinants factors from September 11, 2013 to February 8, 2019 in Debre Berhan Referral Hospital.