Increased viral suppression among people on first line antiretroviral treatment in Ethiopia: Meeting the third 90’s

Background Antiretroviral treatment (ART) is aimed for complete suppression of viral replication but it fails for a variety of reasons. The aim of this study was to determine the prevalence and associated factors of treatment failure among people on first line ART in Amhara region, North east Ethiopia. Methods A cross sectional study was conducted from March, 2018 to July, 2018. Questionnaire survey using a pre-structured questionnaire was taken focusing on demographic data and possible risk factors of antiretroviral treatment failure. Clinical history including baseline characteristics was extracted by reviewing medical records using data abstraction sheet and data was analyzed using STATA version 14. Results A total of 640 clients of all age from 16 health facilities were enrolled in the study. The overall antiretroviral treatment failure was 16.45% from which clinical, immunologic and virologic failure were 0.47%, 13.59% and 3.13% respectively. The viral suppression was 91.09%, but more than half, 29 (50.88%) study participants with high first viral load (>1000copies/ml) were defaulted and not tested for the 2 nd viral load testing. Binary and multivariable logistic regression analysis showed significance association of treatment failure with age at treatment initiation (OR, 1.029), duration on ART (OR, 0.87) and adherence (AOR, 4.22). High proportion of treatment failure was also found in females (62.75%) and in those below primary education (76.47%). Conclusions In conclusion increased viral suppression is observed but the rate of default during 3 month of enhanced adherence counseling is high. The overall magnitude of treatment failure in Amhara region is 16.45%. Fair/poor adherence, older age at treatment initiation and shorter duration on ART are significantly independent factors of treatment failure. Therefore improving client follow up to adherence to treatment should be strengthened. This study was designed to assess the magnitude and associated factors of treatment failure from 16 health facilities in Amhara region. The study found viral suppression of 91.09 after 6 months of ART and 92.34 treatment successes after 3 month of enhanced counseling of clients who had unsuppressed viral load (> 100copies/ml) at 6 month of treatment. However high rate of clients, 50.88%, defaulted from enhanced adherence and counseling was observed in this study which will have great programmatic effect to achieve the third 90’s goal. The overall first line antiretroviral treatment failure was 16.45% from which 0.47%, 13.59% and 3.13% were clinical, immunologic and virologic failures respectively. This finding is slightly lower than a study from Addis Ababa which reported 21% treatment failure of which 1.8%, 15.3% and 4.4% clinical, immunologic and virologic failures respectively [11], 21% immunologic failure was also reported from Debremarkos, Amhara region [12] and another study from Addis Ababa reported 19.8% treatment failure. However the virologic failure in the present study is higher than the study from Addis Ababa that reported 1.3% [5] which could be due to presence of different of adherence status. The finding of the present study is much higher than studies in Gondar, Amhara region, 4.1%, treatment failure [4] and in Bale zone hospitals of Oromia region, 9.8% treatment failure [13]. possible justification for this could be studies the findings.


Introduction
Antiretroviral treatment is recommended for everyone with HIV to help people with HIV live longer, healthier life and to reduce the risk of HIV transmission. Ethiopia accepted the WHO recommendation to provide lifelong ART to all people living with HIV, including children, adolescents and adults, pregnant and breastfeeding women, regardless of clinical status or CD4 cell count. [1]. Antiretroviral treatment is aimed for complete suppression of viral replication. Once effective ART is started, it usually takes 3 to 6 months for a person's viral load to reach an undetectable level. Suppression of viral load to undetectable levels in people living with HIV (PLHIV) using antiretroviral therapy makes less prone to HIV-related illness. However according to a recent global report only 73% of PLHIV were virally suppressed worldwide [2] indicating the global target of 90% viral suppression is yet not being achieved and sub-Saharan Africa has a similar report [3]. show that the magnitude of ART treatment failure in Ethiopia ranges from 4.1% [4] to 19.8% [5]. Antiretroviral treatment fails for a variety of reasons most importantly nonadherence to antiretroviral treatment [6] which is higher in low and middle income countries [7]. Other factors that can contribute to treatment failure include antagonism between some drug combinations, degree of CD4 status before treatment initiation [8], presence of co-infection, type of treatment regimen, body mass index (BMI) [9], old age [10] and other socio economic factors. Therefore, describing the situation in the region may help to minimize unnecessary regimen switch, to improve current practices, thereby improving health outcomes and preventing emergence and transmission of drug resistant strains. Accordingly this study is aimed to assess the magnitude and associated factors related to treatment failure among people on first line ART in Amhara region, North east 4 Ethiopia.

Study Area and Period
The study was conducted in 16 ART sites health facilities (11 health centers and 5 hospitals) from 6 zonal administrations of Amhara national regional State from March 1, 2018 to July 30, 2018. ART clients visiting the health facilities for receiving their first viral load result during the study period were recruited for the study.

Study Design
A cross-sectional study was conducted among all first line antiretroviral initiated clients who have one viral load measurement after at least 6 months of taking ART. Questionnaire survey using a pre-structured questionnaire was taken focusing on demographic data and possible risk factors of antiretroviral treatment failure. Clinical history including baseline characteristics and adherence status was extracted by reviewing medical records using data abstraction checklist. Those who have viral load result greater than 1000 copies/ml were appointed at 3 month for another viral load test to confirm virologic failure.
Immunologic failure for adults and adolescents is assessed by comparing baseline and current CD4 cell count where <100 cells/µL, below baseline, or <50% of peak after taking ART for 6 months is considered as immunologic failure. For children younger than 5 years, persistent CD4 levels below 200 cells/mm or <10 % peak after 6 month of treatment or for children older than 5 years persistent CD4 levels below 100 cells/mm was considered as immunologic failure.

Sample Size Determination
Sample size was determined using the formula for single population proportion by taking 19.8% prevalence of treatment failure [5]. After considering 2.5 design effect and 7% non-response a total of 657 study subjects were proposed and 640 study subjects were 5 consecutively recruited when they attend the clinics for their follow up to receive their first viral load result.
The data was analyzed by STATA version 14 (Statacorp, USA). Frequencies, proportion and summary statistics were used to describe the study population in relation to relevant variables. Odds ratio and P-value were used to assess the presence and degree of association between treatment failure and possible risk factors and P value <0.05 was considered as presence of significant association.

Operational Definitions
Viral suppression: a viral load of <1000copies/mL after 6 months of ART.
Viral re-suppression:-a viral load of >1000 copies/mL after 6 months of ART and < 1000 copies/mL after 3 months of enhanced adherence and counseling.
Virologic failure: a repeated viral load of >1000 copies/mL after 3 months of the first viral load.

Data Quality Control
Data collection was made by trained health professionals and standardized formats were used for data extraction from medical charts at each health facility. Data collection process was supervised by the investigators. Collected data was checked for completeness prior to data entry and data exploration on entered data was made to see unexpected values, outliers, and identify variables which need transformation.

Socio-demographic and Clinical Characteristics
A total of 640 clients of all age were enrolled in the study from which 405 (63.28%) were females. The median age during anti-retroviral treatment (ART) initiation was 32 years ( ±10.8) ranging from 1 to 70 year and the current median age was 38 years (±11.3).
Majority, 370 (57.81%) were between 20 to 35 years of age and 52 (8.1%) were below 19 years old which are not categorized under adults based on WHO age classification [1]. Five hundred one (78.29%) of the study participants were below primary education and 337 6 (52.66%) were married. The mean length of stay before treatment initiation was 8 month (+ 19 month) ranging from < 1 to 120 months but from 124 participants who were tested after launching of test and treat strategy 84 (67.74%) study participants were initiated within 1 month of testing. The mean duration of stay on ART was 7.48 years (±3.75) with minimum 1 and maximum 15 years. The mean baseline CD4 count was 282 cells/mm 3 (±238) and the current mean CD4 count was 515 cells/mm 3 (±246) which showed significance increment from the baseline (p<0.001) and the CD4 change in females was significantly higher than in males (p<0.01).
As indicated in Regarding their adherence 512 (80.25%) was reported to have good adherence.    [11], 21% immunologic failure was also reported from Debremarkos, Amhara region [12] and another study from Addis Ababa reported 19.8% treatment failure. However the virologic failure in the present study is higher than the study from Addis Ababa that reported 1.3% [5] which could be due to presence of different proportions of adherence status. The finding of the present study is much higher than studies in Gondar, Amhara region, 4.1%, treatment failure [4] and in Bale zone hospitals of Oromia region, 9.8% treatment failure [13]. The possible justification for this could be these studies were retrospective studies in which early detection might be missed that underestimate the findings.
The present study found older age at treatment start, short duration on ART and fair/poor adherence were significantly associated and independent predictors of treatment failure.
Higher risk of treatment failure in older age was revealed in the present study in line with findings from Addis Ababa [5] and contrary to studies in Nigeria, Kenya and Thailand that report younger age during ART initiation as risk of treatment failure [14,15] which might be justified as variations in circulating and acquisition of resistance viral strains.
Adherence is an important factor for treatment failure as it is used as indicator of weather the treatment failure is due to improper medication or due to viral factors such as resistance mutations. In our finding clients with fair/poor adherence were found to be 4.22 times higher risk of treatment failure compared to clients with good adherence similar to findings in different parts of Ethiopia, Gondar and Bale [4,13,16] as well as studies in Kenya and Nigeria [17,18]. In the present study clients data recorded by standard checklist assessment and self-report were used to describe adherence which might underestimate the actual scenario and the real situation may be high. On the contrary association of treatment failure in clients with short duration on ART and older age before treatment initiation suggests occurrence of acquired resistant viral strains as these clients are healthy looking and sexual experience which is supported by the finding from Jimma, Ethiopia in which 81.8% of study subjects with virologic failure showed viral mutations [19].

Conclusions
In this study we conclude that the observed increased viral suppression showed Ethiopia is on track to meet the third 90 of WHO target. The rate of default during 3 month of enhanced adherence counseling is high and the overall magnitude of treatment failure in Amhara region is 16.45% which is significantly associated with fair/poor adherence.
Therefore improving client follow up to adherence to treatment should be strengthened and ART program should focus on increasing adherence for clients who had high viral count at 6 month. Older age at treatment initiation and shorter duration on ART are also 12 significantly associated independent factors of treatment failure that indicate urgent need of drug resistance survey in the study area as these suggest acquisition of resistant viral strain. High proportion of treatment failure was also found in females and in those below primary education suggesting ART program should focus on these groups. The study has got approval from Amhara Public Health Institute ethical review board. All study subjects during the study period was informed the purpose of the study and their 13 consent was sought in written.