The Effect of the Same Day Initiation of Antiretroviral Treatment (ART) on Viral Load Suppression among Adults &gt;15yrs. People Living with HIV in public health facilities in Addis Ababa

doi:10.21203/rs.3.rs-3727450/v1

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Research Article

The Effect of the Same Day Initiation of Antiretroviral Treatment (ART) on Viral Load Suppression among Adults >15yrs. People Living with HIV in public health facilities in Addis Ababa

https://doi.org/10.21203/rs.3.rs-3727450/v1

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Background: The same day initiation of antiretroviral treatment among PLHIV with age greater or equal to 15, regardless of their CD4 count can reduce morbidity, mortality, HIV transmission and eventually the incidence of new HIV infection. However, the effect of the same day ART initiation on viral suppression remains contradicting.

Objective: The aim of this study was to determine the effects of the same day ART initiation on viral suppression; and identify predicators of viral suppression in the era of test and treat strategy.

Methods: A quantitative multicenter retrospective cohort study was conducted using routinely collected data in ART clinics during the initial and follow-up visits of clients in 18 public health facilities in Addis Ababa, Ethiopia.

Results: The viral suppression rates at 12^th month among those who started ART on the same day and after seven days diagnosed with HIV were 94.3% with 95% CI: 92.3-96.4 and 90.3 % with 95% CI: 87.1-93.3 respectively. The difference between the two groups was statistically significant (P-value: 0.033) with RR of 1.044 (95% CI: RR: 1.001-1.090). The TDF-based regimen, working functional status, and alive and on ART follow-up status were found to be predicators of viral suppression.

Conclusion & recommendation: The viral load suppression rate among the same day ART started was higher compared to those started ART after seven days, and is consistent with previous studies in other countries. TDF- based regimen, alive and on ART follow-up status, and working functional status were predicators of viral suppression in this study. Strengthening the same day ART initiation with TDF based regimen is critical for prevention of HIV through viral suppression. Improving the quality of ART data is also essential to generate evidence and inform the practice.

Since the occurrence of human immune-deficiency virus/ acquired immunodeficiency syndrome (HIV/AIDS) in 1984, about 40.1 million people have lost their lives and it remains the public health problem. At the end of 2021, about 38.4 million people are estimated to live with HIV. Two thirds of the people who are estimated to live with HIV at the end of 2021 (25.6 million) are in Africa (1). The Eastern and Southern Africa is most affected HIV region in the world with 54 percent of estimated people living with HIV (31).

There was about 1.5 million new HIV infection in 2021, with a declining global trend but less likely to meet United Nations program on HIV/AIDS (UNAIDS) 2030 target of less than 200,000 new infection per year. In the same year, 85% of people living with HIV (PLHIV) know their status and among those who knew their status, 88% accessed anti-retro-viral treatment (ART) treatment. About 92% of people who were on ART virally suppressed(2) . Although large number of people who are living with HIV have been on ART, still there is a significant percentage of PLHIV are not on treatment(3). In 2021, an estimated number of 610,000 people are living with HIV in Ethiopia, with a prevalence of 0.96 %(4). In the continuum of HIV care, 84% knew their status, 78% are on ART and 75% are virally suppressed(5). Currently 480,264 PLHIV are receiving antiretroviral treatment in Ethiopia (6).

Since 2016 world health organization (WHO) recommended countries to adopt the rapid ART initiation strategy, initiating ART within seven days after diagnosed with HIV. Rapid ART initiation could potentially lead to earlier viral suppression through increasing uptake to care, adherence to treatment and retention to care(7). Ethiopia adopted this strategy in all health facilities with ART sites since February 2017(8). However, recent study showed that the magnitude of the same day ART initiation in Ethiopia is as low as 41.9%(9).

Viral load monitoring for adults PLHIV recommended to be done at 6 and 12 months and then annually after initiation of ART(10). According to a study conducted in Tanzania, the prevalence of viral load suppression among adults was 79% at 12 months(11). In Ethiopia, a recent study showed that the overall viral load suppression at 12 months was 91.09% but more than 50% of cases with high viral load during the first viral load test defaulted the antiretroviral treatment and didn’t take the second viral load test(12). Studies conducted in the United states of America, San Francisco, and in Uganda revealed that rapid ART initiation resulted in faster viral load suppression compared to those who initiated ART seven days later diagnosed with HIV(13),(14),(15).

Contrary to these findings, studies conducted in low income settings such as Nigeria, Rwanda and Ethiopia showed that lower rate of viral load suppression at 12^th month among those who started ART on the same day diagnosed with HIV compared to late initiators(16),(17),(18). Factors like adherence to treatment, fear of disclosure, acceptance to ART, baseline test result availability before initiating treatment, care provider’s skill, facility’s infrastructure can negatively influence rapid ART initiation program(19).

In a randomized controlled trial study conducted in Haiti, the viral load suppression among the same day ART initiated was higher (61.1%) compared to those lately initiated ART (after 7 days) which was 51.7% with P value: 0.012(20). In another systemic review of comparative studies in different settings, the viral load suppression was greater at 12 months among those who initiated the antiretroviral treatment on the same day diagnosed with HIV (RR: 1.18, CI 95%: 1.10 - 1.27) compared to those started ART after seven days diagnosed with HIV(9). Contrary to these findings, a study conducted in North West Ethiopia showed that the viral load suppression was suboptimal among the same day initiators of ART (73.4%) compared to those started ART after seven days HIV was diagnosed (83.7%) with adjusted difference of 8% (95% CI: 4.9% to 15.8%)(18). In another study conducted in Rwanda, there was no difference in viral load suppression rates between those who started ART on the same day and those who started ART seven days after HIV diagnosed (adjusted prevalence ratio: 0.98, 95% CI: 0.94-1.03)(17).

The virological status of people living with HIV can be affected by socio-demographic, care seeking behavioral clinical and environmental factors. Sex, Age, Education, Marital status, CD4 count, Body Mass Index (BMI), WHO Clinical Stage, Regimen type, Adherence to treatment, Duration on treatment, and Time ART initiated after HIV diagnosis are factors commonly reported to be associated with viral load suppression(25)(See figure 1.). In a study conducted in Democratic Republic of Congo, the mean viral load was significantly higher in males compared to females. It was also significantly higher in patients with older age, poor adherence and comorbidities, having no severe opportunistic infection, and good adherence to treatment were significantly associated with viral load suppression(13). Whereas, WHO clinical stage and duration on ART was not statistically significant(26). Other similar research works in Ethiopia indicated that being female(27), having a baseline CD4 > 350 cells/mm3, good adherence to treatment and having no recurrent opportunistic infection are independent predicators of viral load suppression(10)(27).

Given contradicting findings on the effects of the same day ART initiation on HIV treatment outcomes and insufficient information on the determinant factors of viral suppression in the test and treat era. Therefore, it was essential to conduct this research in a different setting, public health facilities in Addis Ababa, where the test and treat strategy has been implemented since 2017. We modified the conceptual framework developed by Cochrane collaboration (9) for HIV continuum of care so as to suite the objectives of this research work.

This study tried to answer the following research questions:

Dose the same day ART initiation increases viral suppression rate at 12 months among adult >15 yrs. PLHIV compared to those Started ART after seven days HIV diagnosis confirmed?
What are the factors that affect viral load suppression rate in the era of test and treat strategy?

Research Objectives

Main objective: The primary objective of this study was to determine the effect of the same day ART initiation on viral load suppression among adult >15yrs. PLHIV, and to identify factors associated viral load suppression in test and treat strategy era.

Specific objectives:

To determine whether the same day ART initiation increases viral load suppression rate at 12 months among adults >15yrs. PLHIV compared to those started ART after seven days HIV was diagnosed.
To identify factors associated with viral load suppression at 12 months among adults >15yrs. PLHIV who started ART during test and treat era.

Study Setting፡ Addis Ababa is an administrative and economic capital of Ethiopia, and home for an estimated population of 5.2 million. It has 11 sub-cities and more than 115 functional public health facilities (13 public hospitals and 102 health centers) that provide healthcare services for the public. The aggregate data from district health information system (DHIS2) showed that there are 78 Health centers and 11 public hospitals which are providing ART services. These ART sites compile and sent monthly report to the Addis Ababa Regional Health bureau on a regular base. Including the public health facilities, 114 ART sites use an Enhanced Electronic Medical Record- ART database system (EMR-ART system) developed by ICAP (International Center for AIDS care and treatment Program)- Ethiopia, to collect and manage individual level ART data(29). The study collected the database backup data from 18 public health facilities in Addis Ababa. The list of public facility sites from where the database backup file collected were eight public hospitals: Zewditu Memorial, ALERT, Black Lion, St.Paul, St. Peter, Yekatit-12, Ras Desta Memorial and Gandhi Memorial hospital, and ten public health centers: Efoita, Feres, Hiwotamba, JagemaKelo, Keraneyo, Kirkose, kolfe, Lideta, Mikilayland, and Kolfe Woreda 9 health center. All clients receive ART services in these public facilities free of charge.

Study design

We conducted a multicenter retrospective cohort analysis of the effect of the same day ART initiation on virological outcome among adults ≥ 15yrs of age PLHIV who started ART from 2017 to 2021 in Addis Ababa. We took individuals who started ART within five years of duration as sample size wouldn’t be enough when the exclusion criteria applied. The study used secondary extracted from enhanced standalone EMR- ART database backup files from 18 public health facilities, and merged to a single database.

Study population

Adults with age ≥ 15 years at time of ART enrolment and started ART from January 2017 to February 2021 who were on treatment for a minimum of 12 months, and with at least one documented viral load status at 12th month of treatment were included in this study.

We excluded those transferred in, pregnant, TB and cryptoccocal meningitis cases, and those who were transferred out before 12 months of treatment from the study.

Sample size

To achieve representative sample size of the population who started ART on the same day and after seven days ART initiation for viral load suppression at 12 months, we considered the proportions of the viral suppression at 12 months in North West Ethiopia as estimates 73.4 percent for p1 (the proportion of viral suppression among clients who started ART on the same day diagnosed with HIV), and 83.7 percent p2 (for those who started ART after seven days diagnosed with HIV). With 95% confidence interval, and 80% study power, the sample size calculated using Epiinfo version 7.2.5.0 software. With additional 15 percent to compensate missing records, the total sample size was 616.

Sampling procedure

We collected database back-up files from 8 public hospitals and 10 health centers. The database backup files were collected from each health facility starting from July 2022 to January 2023 at various time during EMR-ART system upgrading task performed by ICAP. Using a database tool known as Microsoft SQL (Structured Query Language) 2019 Express Management Studio, the database backup file for each facility was restored to a separate instance of database, and merged to a single database by querying the different tables and views. During this procedure, we deliberately removed the individual’s full name and phone number from the merged database and inserted Health Facility name to make records confidential and allow analysis by facility type respectively. Then, we further extracted records of individuals who started ART from January 2017 to February 2021. As next step, we created different cascaded views by removing deprecated records, and records of individuals on ART and who were under 15 yrs. of age, transfer in, pregnant, TB and Cryptococci meningitis case at time of ART initiation.

Before the final extraction of the data from Microsoft SQL 2019 express, functional status code was translated, Months on ART, Months Viral Load performed after ART initiation, and number of days elapsed after HIV diagnosis were computed. Using Microsoft Excel 2013, the data set was extracted from SQL database to Microsoft excel. Using add-in tool of MS Excel, ‘Ablebits’, we trans-positioned the individual’s follow up records, and created a single row individual’s longitudinal records.

Data collection tools & procedures

The source of this research data was enhanced Electronic Medical Recording System–ART software. This software upgraded and deployed to a total of 99 public and non-governmental ART service providing sites in Addis Ababa by ICAP in 2018. It was initially developed and deployed by Tulane University in 2015 to ART sites in Ethiopia. Using free version of Microsoft SQL 2019 Express, we were able to restore each database file of 18 public health facilities and merged to a single database instance.

Data quality

Those deprecated (not usable any more) records were removed from the merged database. Unique ART number and Follow-up date were used to remove the duplicated initial and follow-up records. Since there was no time to correct records with invalid data with the paper register (taking it as a reference), we removed a total of 236 individual records before transferring the final dataset to SPSS version 20 statistical software. To understand the volume of data completeness or extent of the missing values to each independent variable, we applied multiple imputation pattern analysis technique using SPSS.

Study Variables

The same day ART initiation was the exposure variable and computed as the difference between the dates by which ART was initiated and the individual was diagnosed to have HIV (Date HIV diagnoses confirmed). For analysis purpose, we categorized ART initiation date of the participant into two groups, those participants who started ART on the same day, and those who started ART after seven days diagnosed to have HIV. The study outcome variable was viral load status at 12th month. The viral load status was recorded as ‘suppressed or ‘undetectable’ in the EMR database if viral load count was less or equal to 1000 copies per one milliliter (ml) of blood. Whereas, the viral load status was labeled as ‘unsuppressed’ or detectable’ when the viral load count was greater than 1000 copies per 1 ml of blood. The viral load count was not recorded for all individuals along with the viral load status in the database, and thus couldn’t further categorize the level of viral load status among the study participants. The independent variables included in the study were sex, age at enrollment, educational level, marital status, baseline CD4 count, Body Mass Index (BMI), WHO Clinical Stage, Functional status, ART regimen, Adherence, and Months on ART. For the dependent variable of the 12th month viral load status, we included those records with documented viral load status at 10th, 11th 12th, 13th, 14th and 15th months after starting ART. We categorized the values of the dependent and independent variables to the appropriate group for analysis and comparison with other studies.

Data Analysis

Data were extracted form enhanced EMR-ART and merged to a single database on Microsoft SQL 2019 Express. The data was imported to Microsoft 2013 excel for further data cleaning and transposed the follow-up records to create the longitudinal record for each individual case on ART treatment. After importing the data to SPSS version 20, we transformed the data to be ready for analysis. Descriptive statistics were used to characterize the dependent and independent variables of the two groups. We conducted bivariate analysis to examine whether there was an association between each independent variable of the study with viral load status. In addition, multi-variables logistic regressions analysis was conducted to adjust for potential confounders of the predicators of viral load suppression. Comparisons of the proportion of viral load suppression between the same day and after 7 days ART initiators were achieved using Pearson’s chi-square test.

To conduct the data analysis for the secondary objective, we examined the pattern of missing values among the independent variables using the multiple imputation analysis technique, and decided which variable to include or exclude from the multivariable analysis. As a result, we found that the baseline CD4 count variable had missing value of 88.7 percent (721/812), and occupation had 88.1%( 716/812) of missing values. The missing values for initial WHO clinical stage was 37.9 (308/812). Initial BMI with 33% (268/812), Initial functional status with 27.3% (222/812), Education with 13.1%( 111/812), Marital status with 11.3% (92/812) and religion with 7.6 Percent (62/812) of the records had missing values. The other independent variables Sex, Age, Regimen, and Facility type had no missing values. Therefore, we excluded those variables with missing values more than 30 percent from the multi-variable analysis.

Operational definitions

Based on the nature of the data and the World Health Organization (WHO) standards, we defined the exposure and the outcome variables as follows

Viral suppression at 12th month: In this research work, the viral load suppression is achieved if a viral load count is 1000 or lower copies per ml at 12th after initiation of ART. Because of the viral load test service availability and accessibility in Ethiopia, especially prior to COVID 19 era, it was difficult to get documented viral load test result exactly at 12 month. Thus, we considered test results document at 10th, 11th, 12th, 13th, 14th and 15th month of antiretroviral treatment as Viral load test at 12th month.
The same day ART initiation: When PLHIV starts ART on the day he or she is diagnosed to have HIV infection.

Ethical considerations

Ethical clearance was obtained from Addis Continental Institute of Public health and shared with Addis Ababa Regional Health Bureau. The individual identifiers were masked or de-identified before data extraction and manipulation started.

A total 4,375 records of individuals with extracted from enhanced EMR-ART databases of the public health facilities. However, significant number of the individual’s follow up records were either deprecated (marked as not for use) or duplicated (more than one follow up records with the same follow-up date and unique ART number). In addition, there were records with default system date (missing value) for HIV diagnosis date confirmed. As a result, we removed all those anomalies from the dataset and identified 2,292 unique individual’s records. Since the primary objective of this study was to compare the viral suppression rate among the two groups: those who started ART on the same day and those who started ART after seven days HIV was diagnosed, we removed those records of individuals who started ART in the first week (1–7 days) after they had been diagnosed to HIV in their blood. As a result, we identified 1,701 records who started ART either on the same day or after 7 days diagnosed with HIV. Finally, we included 812 individual records with documented viral load status 12 months in the study and become ready for analysis (see Fig. 2).

Socio-demographic characteristics

Those who started ART on the same day they were diagnosed to have HIV constituted 54% (439/812) of the study participants, and the rest (46%) were those who started ART after seven days diagnosed with HIV. Out of the total 812 study participants, 63.1 percent (512) and 36.9 percent (300) were from public hospitals and health centers respectively. In both study groups, females constituted 58.3 percent of those who started ART on the same day diagnosed with HIV, and 51.7 percent of those study participants who started ART seven days after diagnosed with HIV. The median age of the study participants at enrollment to HIV care for those who started ART on the same day and after seven days were 36 yrs. and 38 yrs. respectively.

In both study groups, the majority of the study participants had a ‘working’ functional status at the time of ART initiation which was 91.9% for those who started ART on the same day, and 86.5% for those who started ART after seven days. Ambulatory and Bedridden functional status at enrollment constituted 6.8% and 4.6% for those who started ART on the same day, and 8.9% and 1.3% for those who started ART after seven days. Individuals who were never married or widowed or divorced (Single) constituted 52 and 51.2 percent of those study participants in the two groups, who started ART on the same day and after seven days, respectively.

The majority (85.9% and 88.3%) of both study groups were literate i.e. either completed tertiary or secondary or primary school. The remaining 14.1 and 11.7 percent of the participants who started ART same day and after 7 days respectively, had received no education. In addition, almost 91% of the study participants in both groups were Christian by religion. The remaining 9 percent of the participants in both groups were Muslims by religion. About 70 percent of those who started ART on the same day, and 66.7 percent of those started after seven days were either self- employed or employees of governmental or non-governmental organizations. The remaining 30 and 33.3 percent of the two groups were unemployed (see table.1). Facility type and functional status were significantly associated with initiation of ART on the same day.

Clinical characteristics of the study participants

Excluding those records with missing values, 68.8% of those who started ART on the same day and 46.8% of those started ART after seven days were at Stage 1 of the disease when they started ART (based on the WHO clinical Staging). Among those study participants with recorded WHO clinical stage at time of initiation of ART, 2.9 and 18 percent of those who started ART on the same day and after seven days of HIV diagnosis were at WHO Clinical Stage 4 of the disease respectively.

Table 1

Sociodemographic characteristics of the study participants who started ART from Jan. 2017 to Feb.2021 in Addis Ababa by exposure group
Variable	The same day ART Started (n = 439)		ART started after 7 days (n = 373)
Variable	Frequency	Percentage (95% CI)	Frequency	Percentage (95% CI)	P-value
Facility type					0.001
Hospital	253	57.6(52.9–62.2)	259	69.4(63.9–74.3)
Health center	186	42.4(37.8–47.1)	114	30.6(25.7–36.1)
Sex					0.061
Female	256	58.3(54-63.5)	193	51.7(46.7–57)
Male	183	41.7(36.5–46)	180	48.3(43-53.3)
Age (median)		36 (35–38)		38 ( 37–40)
Functional Status					0.029
Working	285	91.9 (88.8–94.7)	243	86.5(82.2–90.4)
Ambulatory	21	6.8(4.2–10)	25	8.9(5.7–12.8)
Bedridden	4	1.3(0.3–2.6)	13	4.6(2.1–7.3)
Marital Status					0.824
Single	196	52 (47.2–57)	176	51.2 (45.1–56.4)
Married	181	48 (43-52.8)	168	48.8 (43.6–54.9)
Education					0.352
Literate	324	85.9(82.2–89.1)	287	88.3(84.4–92)
No education	53	14.1(10.9–17.8)	38	11.7(8.0-15.6)
Religion					0.937
Christian	365	91(87.7–93.5)	318	90.9 (87.8–93.6)
Muslim	36	9(6.5–12.3)	32	9.1(6.4–12.2)
Occupation					0.729
Employed	28	70 (55.0-82.5)	38	66.7(54.4–78.9)
Unemployed	12	30(17.5–45.0)	19	33.3(21.1–45.6)

The majority of the study participants, 59.1 percent of those who started ART on the same day and 60.2 percent of those who started ART after seven days, had normal body mass index. The rest had BMI either categorized as underweight or overweight in both study groups. Among those study participants with a recorded baseline CD4 count, 25 and 18 percent of those who started the same day and after seven days had 350 or greater CD4 cells per ml at time of enrollment respectively. In both groups, smaller proportion of the study participants (16 percent of the same day, and 21.4 percent of those started ART after seven days) had CD4 count less than 200 cells per ml. In both study groups, majority of them were receiving Tenofovir (TDF) - based regimen followed by Zidovudine- AZT based antiretroviral regimen. More than 94 percent of individuals who started ART on the same day, and 91 percent of those who started ART after seven days were initiated with first line regimen that contains combination of TDF (Tenofovir), 3TC (Lamivudine) and DTG (Dolutegravir) drugs (see Table 2). In both groups, less than 10 percent of the participants were initiated with antiretroviral combination of either ABC (Abacavir) based or other first line antiretroviral regimens.

Table 2

Clinical characteristics of the study participants who started ART from Jan. 2017 to Feb.2021 in Addis Ababa by exposure group
Variable	The same day ART Started (n = 439)			ART started after 7 days (n = 373)
Variable	Frequency	Percentage		Frequency	Percentage
WHO Stage(initial)							< 0.001
Stage 1		187	68.8(63-74.3)		109	46.8(40.5–52.8)
Stage 2		35	12.9(9.6–16.9)		26	11.2(7.3–15.0)
Stage 3		42	15.4(11.4–20.5)		56	24(19.0-29.6)
Stage 4		8	2.9(1.1–5.1)		42	18(13.0-23.2)
BMI (Initial)							0.886
Normal(18.5–24.9)		165	59.1(54.3–65.5)		160	60.2(54.1–65.8)
Underweight (< 18.5)		58	20.8(16.3–25.5)		57	21.4(16.2–26.2)
Overweight(Greater 24.9)		56	20.1(15.4–23.7)		49	18.4(13.9–22.9)
CD4(Baseline)							0.729
<200 cells per ml		8	16(6–26)		9	21.4(9.5–34.9)
200–349 cells per ml		17	34(20.7–48.0)		15	35.7(21.4–50.0)
> 350 cells per ml		25	50(36–62)		18	42.9(28.6–57.1)
ART Regimen							0.066
TDF based		416	94.8(92.9–96.8)		341	91.4(88.3–94.1)
AZT based		14	3.2(1.6–4.8)		16	4.3(2.4–6.6)
ABC based		3	0.7(0.0-1.6		6	1.6(0.5–3.2)
Other		6	1.4(0.5–2.5)		10	2.7(1.3–4.6)
Adherence (last visit)							0.075
Good		347	79(74.9–82.7)		316	84.7(81.1–88.7)
Fair		2	0.5(0.0-1.1)		1	0.3(0.0-1.1)
Poor		90	20.5(17.1–24.5)		56	15(11.1–18.7)
Follow-Up (last visit)							0.732
Alive & on ART		434	98.9(97.7–99.7)		370	99.2(98.1–100)
Lost or Restart		5	1.1(0.3–2.3)		3	0.8(0.0-1.9)
Viral suppression at 12 month							0.033
Suppressed		414	94.3(92.0-96.4)		337	90.3(87.1–93.0)
Unsuppressed		25	5.7(3.6-8.0)		36	9.7(7.0-12.9)

Among those study participants who started ART on the same day, the adherence status at 12 month (last visit) was ‘Good’ for 79 percent of them followed by 20% ‘Poor’ and 0.5 percent ‘Fair’. Similarly, majority of the last visit adherence status of those who started ART after 7 days was ‘Good’ (84.7 percent). The follow up status (of those who started ART on the same day and after seven days) was ‘Alive and on ART’ for 99 percent of the participants in both groups. Only 1.1 and 0.8 percent of those who started ART on the same day and after seven days, respectively had recorded follow up status of either ‘Lost’ or ‘Restart’ (See Table 2). WHO clinical staging (P-value: <0.001) and viral suppuration rate at 12th month (p-value: 0.033) were significantly associated with initiation of ART on the same day.

Viral load suppression proportions

The primary objective of this study was to test whether the viral suppression proportion of individuals who started ART on the same day had statistically significance difference compared to the viral suppression proportion of individuals who started ART after seven days.

The null and alternate hypotheses in this study tested were:

H₀: There is no viral load suppression proportions difference at 12 months between those individuals who started ART on the same day and after seven days diagnosed with HIV.

H_A: There is a difference in viral load suppression proportions at 12 months between individuals who started ART the same day or seven days after diagnosed with HIV.

Out of the total records with viral load status documented at 12 months, 51.1percent (439/812) were those who started antiretroviral treatment on the same day diagnosed with HIV (exposed group). Whereas the rest 48.9 percent (373/812) were those who started ART after seven days diagnosed with HIV (unexposed group).

Table 3

Viral suppression proportions at 12 months among exposed and unexposed groups
Variable	Same day (n = 439)				P-value
	Frequency	Percentage	Frequency	Percentage
Viral load status at 12 month					0.033
Suppressed	414	94.3(92.3–96.4)	337	90.3(87.1–93.3)
Unsuppressed	25	5.7(3.6–7.7)	36	9.7(6.7–12.9)

Among the exposed group, the viral suppression proportion at 12 month was 94.3 percent (414/439) with 95% CI: 92.3–96.4 percent, and the remaining 5.7 percent (25/439) were not virally suppressed (with 95% CI: 3.6–7.7 percent). For the unexposed group, 90.3 percent (337/373) with 95% CI: 87.1–93.3 percent had viral suppression at 12 months of treatment whereas 9.7% (36/373) with 95% CI: 6.7–12.9 percent were not virally suppressed (See Table 3).

The absolute difference of viral load supersession proportions between the same day and after 7 days groups was 4 percent. The relative risk of viral suppression of those individuals who started antiretroviral treatment on the same day HIV diagnosed (RR) was 1.044 (95% CI: 1.001–1.090) (with p-value: 0.033) higher compared to those who started ART after seven days HIV was diagnosed. The relative risk of viral load un-suppression among those who started ART on the same day was 0.59 with 95% CI: 0.34–0.99, which was 41% lower compared to those started ART the seven days after diagnosed with HIV.

The observed difference in the viral load suppression between the exposed and unexposed group was statistically significant. The risk difference between those who started ART (0.94) on the same day and those who started ART after seven days (0.90) was 0.04, implying that there was 4 percent excess chance of being virally suppressed compared to those who started ART after seven days diagnosed with HIV. This study showed that 4.15% of virally suppressed PLHIV were attributable to initiation of ART on the same day HIV was diagnosed.

Factors associated with viral suppression at 12th month

A total of 812 records found with documented viral load status at 12th month, of which 92.5 percent (751) of they were virally suppressed or have HIV RNA (Ribonucleic Acid) copies less or equal to 1000 copies per ml in their blood. The proportion of viral load non-suppression among all the study participants was 7.5 percent (61/812). The majority of the participants in both groups, virally suppressed and unsuppressed, were from hospitals (62.6 and 68.9 percent).

Table 4

Characteristics of independent variables for viral suppression
Variable	VL ≤ 1000 copies/ml (n = 751)	VL > 1000 copies/ml (n = 61)	P-Value
	n( row%)	n(row%)
Facility Type			0.329
Hospital	470(62.6)	42(68.9)
Health center	281(37.4)	19(31.1)
Sex			0.643
Female	417(55.5)	32(52.5)
Male	334(44.5)	29947.5)
Age at enrollment			0.404
40 and plus	270(38.5)	17(32.7)
15–39 yrs.	431(61.5)	35(67.3)
Marital Status			0.029
Single	337(50.4)	35(66)
Married	331(49.6)	18(34)
Education			0.486
Literate	565(86.8)	46(90.2)
No education	86(13.2)	5(9.8)
Religion			0.146
Christian	630(90.5)	53(96.40
Muslim	66(9.5)	2(3.6)
Functional Status			0.004
Working	497(90.4)	31(75.6)
Ambulatory	40(7.3)	6(14.6)
Bedridden	13(2.4)	4(9.8)
WHO Stage(initial)			0.254
Stage 1	278(59.9)	18(43.9)
Stage 2	54(11.6)	7(17.1)
Stage 3	87(18.8)	11(26.8)
Stage 4	45(9.70	5(12.2)
BMI (Initial)			0.297
Normal	304(60.1)	21(53.8)
Underweight	103(20.4)	12(30.8)
Overweight	99(19.6)	6(15.4)
CD4(Baseline)			0.133
<200 cells per ml	15(17)	2(50)
200–349 cells per ml	32(36.4)
> 350 cells per ml	41(46.6)	2(50)
ART Regimen			< 0.001
TDF based	714(95.1)	43(70.5)
AZT based	14(1,9)	16(26.2)
ABC based	7(0.9)	2(3.3)
Other	16(2.1)
Adherence (last visit)			0.517
Good	616(82)	47(77)
Fair	3(0.4)
Poor	132(17.6)	14(23)
Follow up (last Visit)			0.001
Alive and OnART	746(99.3)	58(95.1)
Lost or Restart	5(0.7)	3(4.9)

Females were majority in both groups of the study with documented viral load status, 55.5% of those virally suppressed group and 52.5% of unsuppressed group. In both groups, majority of the participants were in the age group between 15 and 39 yrs. at enrollment. Almost half of the study participants among the group with viral load suppressed at 12 months, had marital status of single and married. However, majority had single marital status among the group whose viral load was not suppressed at 12 months. Majority of the study participants (> 86%) were literate in both groups. Christianity and working functional status were the dominant faith and functional status of the study participants in both groups. In both groups, majority were in Stage 1 of the disease at enrollment followed by Stage 3, 2 and 4. Similarly, body mass index of normal range (18.5–24.9), CD4 count 350 or greater, and TDF based ART regimen were majority in both groups. ‘Good’ adherence and ‘alive and on ART’ were the dominant adherence and follow up status of the study participants in both groups in their last follow up visits (See Table 4).

We conducted a bivariate analysis using binary logistic regression to explore whether there was an association between each independent variable with viral load suppression. The result showed that Sex, Age, Education level, WHO clinical Stage (initial visit), Baseline CD4 count, initial Body Mass Index and Adherence to ART at 12 months were not associated with the viral load suppression among the study participants (see Table 4). Whereas, single marital status with RR 1.91 95% CI: 1.06–3.44 (P-value: 0.31), Working functional status with RR 0.20 95% CI: 0.06–0.66 (P-value: 0.008), TDF based regimen with RR: 0.124 95% CI: 0.07–0.24 (P-value: <0.000), and Alive and on ART follow up status with RR: 0.13 95% CI: 0.03–0.56 ( P-value: 0.006) had statically significant association with viral load suppression in the test and treat era.

A multi-variable logistic regression analysis was conducted on selected variables using the multinomial regression model. The result showed that working functional status with adjusted RR: 7.58 95% CI: 1.80-31.88 ( p-value = 0.006), TDF based regimen with adjusted RR: 11.02 95% CI: 4.59–26.45 (P-value: <0.001) and Alive and on ART follow up status at 12 month with adjusted RR: 10.11 95% CI: 1.43–71.60 (p-value: 0.021) were significantly associated with viral load suppression of individuals at 12 month of treatment (see Table 5).


Variable	Viral suppression n(439)	Crude OR(95% CI)	p-Value	Adjusted OR(85% CI)	p-Value
Facility Type
Hospital	470(62.6%)	0.76 (0.43–1.33)	0.331	0.49(0.186–1.31)	0.155
Health Center	281(37.4%)	Ref
Sex
Female	417 (55.5%)	0.88 (0.52–1.49)	0.643	0.85(0.36–1.99)	0.703
Male	334(44.5%)	Ref
Age Group
15 to 39 yrs	431(61.5%)	0.78(0.43–1.41)	0.405	0.71(0.30–1.65)	0.42
40yrs and plus	270(38.5%)	Ref
Marital Status
Single	337(50.4%)	0.52 (0.29–0.94)	0.031	0.72(0.31–1.63)	0.42
Married	331(49.5%)	Ref
Functional Status
Working	497(90.4%)	0.20(0.06–0.66)	0.008	7.58(1.80-31.88)	0.006
Ambulatory	40(7.3%)	0.49(0.12-2.0)	0.318	5.09(0.85–30.66)	0.076
Bedridden	13(2.4%)	Ref
ART Regimen
TDF based	714(95.1)	0.12(0.07–0.24)	< 0.001	11.02(4.59–26.45)	< 0.001
Other	37(4.9%)	Ref
Adherence
Good	616(82%)	0.74 (0.39–1.38)	0.336	1.40(0.53–3.67)	0.494
Fair or Poor	135(18%)	Ref
Follow-up Status
Alive and On ART	746(99.3%)	0.13(0.03–0.56)	0.006	10.11(1.43–71.60)	0.021
Lost or Restart	5(0.7%)

Providing antiretroviral treatment to HIV diagnosed individuals and achieving viral suppression as early as possible in the course of the treatment is one of preventive strategies for HIV/AIDS. The aim of this study was to determine the effect of same day ART initiation on the viral load status at 12 months on treatment. To achieve this, we compared the proportions of the viral load suppression at 12th months between the two groups: those who started ART on the same day and those who started ART after seven days. To meet the second objective, we analyzed the data using binary and multiple variable logistic regression models and identified predicators of viral load suppression in this study population group.

The proportion of viral load suppression at 12th month among those who started HIV on the same day was significantly higher compared to those started ART after seven days (P-value: 0.033). Tenofovir base treatment regimen, ‘Working’ functional status of individuals at enrollment to care, and ‘Alive and on ART’ follow up status were found to be predicators of viral load suppression in this study group.

Viral load suppression at 12th month among those who started ART on the same day HIV diagnosed was significantly higher compared to the viral suppression among those who started after seven days. The risk of being virally suppressed among those individuals who started ART on the same day was 1.044 times higher compared to those started ART seven days after diagnosed to have HIV (RR: 1.044 95% CI: 1.003–1.09). This finding goes with a randomized clinical trial conducted in Haiti and a systematic review of the effects of Rapid ART initiation on treatment outcomes.

On the other hand, the study finding was not consistent with the result of previous similar study conducted in Northwest Ethiopia, South Africa (31) and Rwanda. This might be due to difference in study period in relation to the time when the test and treat strategy implementation launched in the respective countries. For example in Ethiopia, the test and treat strategy was launched in 2017 which could affect the study population type included in the study as it was too early to convince the health care providers to adopt the strategy and apply to all patients eligible for the same day treatment.

Currently, the proportion of individuals who started ART on the same day reached to 65 percent in Ethiopia (33). In addition, the introduction of a new initiative called Appointment Spacing Model (ASM) could have contributed to better viral load monitoring due to efficient utilization of available resources. The variation of the study settings in many ways could have contributed for the contradicting findings.

However, in this study the statistical significance of the difference of the proportions of viral load suppression between the two groups was not strong with RR: 1.044 (95% CI: 1.001–1.090) compared to systematic review of other studies (RR: 1.18, CI 95%: 1.10–1.27). This could be due to relatively low uptake of the same day ART initiation strategy and limited viral load monitoring practice by the public health facilities due to the shift of viral load testing sites to COVID testing center during COVID 19 era. Despite the deployment electronic data exchange interoperability platform for viral load test requesting and result exchange between ART sites and testing laboratory, the actual viral load count was not properly recorded in the database and we couldn’t analyzed the actual count of RNA copies per ml for each study participant.

In this study, the viral load suppression proportion at 12th month (92.5%) was similar to another study conducted in Ethiopia (12). However, this finding was higher compared to the viral suppression rate reported by a similar study in Tanzania (11). The implementation of the same day ART initiation strategy and change in ART regimen could be explanation for the observed difference.

We explored factors associated with viral load suppression at 12th month after ART started among those individuals with documented viral load status. The bivariate analysis result showed that individuals with single marital status, a working functional status at enrollment, Tenofovir based antiretroviral regimen, and alive and on ART follow-up status were associated with higher proportion of viral load suppression in the study population.

However, with multivariable analysis using multinomial logistic regression model, it showed that single marital status was not associated with viral load suppression with adjusted RR: 0.72(0.31–1.63) and P-value: 0.42. However, the working functional status, Tenofovir based regimen and alive and on ART follow up status were found to predicators of viral load suppression at 12 month of antiretroviral treatment. Tenofovir based antiretroviral regimen has better efficacy compared to Zidovudine based regimens (34). This finding was comparable with a study conducted in Lesotho that showed higher rate of viral suppression for patients who were on Tenofovir –based ART regimen (32). We couldn’t include BMI, occupation, religion, education level, CD4 count and WHO Clinical staging due to high volume of missing values.

Limitations and strength of the study

This study provides valuable findings to inform policy makers, and HIV programs on the test and treat strategy to prevent HIV infection through achieving viral suppression among people living with HIV at 12 month. We also demonstrated how to use routinely collected ART data with electronic format for research purpose. However, since the study design was retrospective cohort, we relied on available data on electronic format. Data completeness of baseline clinical, sociodemographic and follow up data was challenging to explore those independent variables as the data set had high volume of missing data and we were unable to include in multivariable logistic regression to determine the predicators of viral suppression as it negatively influence the model and its outcomes. Thus, supervision on the data quality is critical.

Viral load suppression among the same day ART started individuals was significantly higher compared to those who started ART after seven days diagnosed with HIV and this finding was consistent with other randomized clinical trials and evidence generated by WHO. Furthermore, this study showed that Tenofovir–based ART regimen, working functional status and alive and on ART functional status were found to be predicators of viral load suppression in test and treat era. However, the quality of routine ART data was low- with high percentage (> 25% missing values) for WHO clinical stage, CD4 count, educational level, marital status and occupation. Thus, we couldn’t include them in the multivariate logistic regression model for multi variable analysis.

Recommendations

Since the same day ART initiation increased viral suppression at 12^th months or at least it is not inferior in this study population compared to those started ART after seven days, it is critical to work towards strengthening the implementation of the same day ART initiation by health care providers in all the public health facilities improving the current coverage of 65% towards achieving the UNAIDS the three 95% targets. TDF-based regimen is one of predicator of viral suppression. Therefore, it is important to further study on how the first line to be selected in order to achieve viral suppression with minimal adverse effects. Generating enough evidence is critical for MOH to shift patient from other regimen to Tenofovir-based regimen to bring viral load suppression within a year of antiretroviral treatment. Initial working and alive and on ART functional and follow up status (respectively) PLHIV who are on ART were predicators of viral load suppression. Thus, we recommend MOH to track and monitor test and treat strategic intervention to reach to the 95% target by initiating ART as early as the same day in all public health facilities that provide ART services. Despite the digitization of ART service in public health facilities, data completeness the medical records was very low-reaching to 88% of missing values for some sociodemographic and clinical variables. The data quality issues with the routine ART data which were collected during the initial and follow up visits of patients to ART clinic made the evidence generation task difficult. Thus, we recommend the MOH and Addis Ababa Regional Health bureau to give adequate emphasis on data completeness of the medical records of PLHIV who are on ART in the public health facilities.

3TC	Lamivudine
AIDS	Acquired Immuno- Deficiency Syndrome
ART	Antiretroviral Treatment
AZT	Zidovudine
BMI	Body Mass Index
CI	Confidence Interval
DHIS2	Digital Health Information Software
TDF	Tenofovir
EFV	Efavirnez
EMR	Electronic Medical Record
FMOH	Ministry of Health
HIV	Human immuno- deficiency Virus
ICAP	International Center for AIDS Care and Treatment Programs
PLHIV	People Living with HIV
RR	Relative Risk
SQL	Structured Query Language
TB	Tuberculosis
TDF	Tenofovir
WHO	World Health Organization

Acknowledgement

First and for most I would like to thank Addis Continental Institute of Public Health and the IRB for the opportunity and ethical clearance to collect data and conduct this research work. I am also grateful to my Advisors Dr. Semira Abdelmenan and Dr. Ismael Ahmed for their meticulously reviewing my research work from the time of title selection till the completion of my final work. I am also thankful to Addis Ababa Regional Health Bureau and Public Health Facilities for allowing me access to extract data for my research work. I also appreciate ICAP staff, especially Fekade Zebere for his support during ART data collection. I am also very grateful for my lovely wife Mrs. Genet Getachew from FMOH HIV Prevention and Control Lead Executive Office, Care and Treatment Program for her technical assistance during ART data analysis. Last but not least, I would like to thank my son Aaron Girma and my daughter Soliana Girma for their lovely and encouraging words during my research work.

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No competing interests reported.

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The Effect of the Same Day Initiation of Antiretroviral Treatment (ART) on Viral Load Suppression among Adults >15yrs. People Living with HIV in public health facilities in Addis Ababa

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Abstract

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Introduction

Research Objectives

Methods

Result

Socio-demographic characteristics

Clinical characteristics of the study participants

Viral load suppression proportions

Factors associated with viral suppression at 12th month

Discussion

Limitations and strength of the study

Conclusion

Recommendations

Abbreviations

Declarations

References

Additional Declarations

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