RETRACTED ARTICLE: Magnitude and Determinants of Virological Failure Among Patients >15 Years on Anti-Retroviral Therapy in Rural Lesotho Between 2015 and 2019 – A Retrospective Cohort Study

Abstract

Background

Lesotho has the second-highest HIV prevalence globally at an estimated 23%, with approximately 87% of the population between 15 and 59 years of age reported to be receiving antiretroviral treatment. There is an urgent need to increase access to effective ART due to increasing rates of first- and second-line treatment failure. Sustaining successful treatment and limiting the development of virological failure is essential, hence the need for early detection of increased viral load indicating drug resistance or rapid progression of viral replication.

Aim

The aim of the study was to determine the proportion of patients with HIV with virological failure and to identify factors associated with virological failure in two districts of Lesotho.

Methods

A retrospective cohort study was conducted in two districts (Butha-Buthe and Mokhotlong) in Lesotho. Data for all patients (age ≥15 years) in the viral load (VL) monitoring database with at least two consecutive viral load results between December 2015 and December 2019 from 22 health facilities were extracted. Descriptive data were presented using tables and figures. Bivariate and multivariate analyses were performed. A p-value < 0.05 was considered a statistically significant association.

Results

Only 4% (n = 913) of the study participants had virological failure. Longer time on treatment >65 months (AOR: 1.85 CI: 1.59–2.15) and being on second-line ART regimen (AOR: 75.23 95% CI: 75.00–99.15) were significantly (p < 0.001) associated with virological failure.

Conclusion

Virological failure among the study participants is lower compared to other settings. The study identified duration on treatment, treatment regimen as high risk for virological failure. Targeted interventions should be developed for these high-risk group individuals, with continuous monitoring of virological response and appropriate drug switching to clients to achieve improved outcomes.

Keywords:

• Lesotho
• HIV prevalence
• highly active antiretroviral treatment
• virological failure

View retraction statement:

Magnitude and Determinants of Virological Failure Among Patients >15 Years on Anti-Retroviral Therapy in Rural Lesotho Between 2015 and 2019 – A Retrospective Cohort Study [Retraction]

Introduction

HIV/AIDS continues to be the leading cause of morbidity and mortality in sub-Saharan Africa (SSA),¹ despite the region having seen a massive increase in the coverage of antiretroviral treatment (ART). The number of people living with HIV (PLHIV) receiving ART increased rapidly across SSA to an estimated 27.5 million by the end of 2020 from 17.1 million in 2015.²

Lesotho is a land-locked country surrounded by South Africa and has the second-highest HIV prevalence globally at 22.7%.³ Data from the 2020 Lesotho household-based national survey (LePHIA) showed that approximately 324,000 persons aged 15–59 years living with HIV. Women had significantly higher prevalence (27.4%; 95% CI 26.3–28.5) than men (16.7%; 95% CI 16.7–18.8). Prevalence peaked at 43.4% among men aged 45–49 years and at 46.5% among women aged 40–44.⁴

Lesotho was the first country in Sub Saharan Africa (SSA) to adopt the World Health Organization (WHO) recommendations for universal initiation of ART for all HIV-positive persons, regardless of CD4 count (ie, “Test and Start”) resulting in the country achieving the 90-90-90 targets among adults living with HIV- 90.1% of PLHIV aged 15 to 59 years (91.4% of women and 88.1% of men) are aware of their HIV status; 96.9% (97.5% for women and 95.8% for men) of PLHIV between the ages of 15 and 59 who are aware of their HIV status say they are currently taking ART and 91.5% (92.2% among women, 90.2% among males) of PLHIV aged 15 to 59 who indicate current use of ART are virally suppressed.⁵

Furthermore, Lesotho was one of the first nations to decentralize ART initiation and follow-up to nurse-led health centers on a nationwide basis.⁶ This was made possible by the introduction of national ART guidelines for nurses working in primary healthcare settings.⁶ HIV testing and treatment coverage has significantly improved in recent years due to rapid scale-up and decentralization of ART.⁷

ART has transformed HIV into a chronic condition and resulted in an increased life expectancy.⁸ Increased life-expectancy and the ART predispose patients to develop other co-morbid conditions of lifestyle. In addition, the scarcity of adequately trained health professionals and the increased workload due to increased volume of patients compromises the quality of care received by these patients. The combination of the above factors increases the risk of patients developing virological resistance. Simultaneously, there is an urgent need to increase access to effective ART due to increasing rates of first- and second-line treatment failure.

Sustaining the success of ART and limiting the development of virological resistance is essential. Viral load (VL) testing is the recommended gold standard by the World Health Organization (WHO) for tracking patient response to ART, for early detection of virological failure, and to reduce the risk of first-line ART regimen medication resistance.⁹ The WHO recommends routine VL monitoring as the preferred option to identify treatment failure on patients taking ART in resource-limited settings (RLS).⁹ The recommendation was based on evidence that other clinical and immunological monitoring, such as CD4 counts, are unreliable proxies for VL suppression.¹⁰

The roll-out of routine VL monitoring commenced in November 2015 and started in Butha-Buthe district hospital’s ART clinic. The rural clinics of the district began sending patients’ blood samples to the hospital laboratory for routine VL monitoring in June 2016.¹¹ The schedule for routine VL monitoring follows current National Guidelines of Lesotho with a VL done after the first 6 months on ART and, if suppressed, yearly thereafter. In the case of unsuppressed VL (≥1000 copies/mL), the guidelines recommend enhanced adherence counselling with a follow-up VL after 8–12 weeks.¹²

Although Lesotho met all the 90-90-90 target and surpassed the overall target for 2020 of having more than 73% PLHIV in all age achieving viral suppression, almost 20% of PLHIV in Lesotho still have an unsuppressed viral load.⁵

The purpose of this study was to ascertain the magnitude of ART virological failure and to determine the associated risk factors in two rural districts (Butha-Buthe and Mokhotlong) in Lesotho. We used the following definitions for virological failure and virological failure: virological failure is defined plasma viral load 1000 copies/mL based on two consecutive viral load measurements after 2–3 months of enhanced adherence support.¹² Treatment failure may be virological (failure of viral suppression or rebound of plasma HIV-1 RNA), immunologic (falling CD4) or clinical (progression to new AIDS-defining illness). The typical progression of virological failure is that virological failure develops first followed by immunologic failure and then clinical failure. This progression is the reason that viral load monitoring is the preferred tool for assessing ART success.¹²

Methods

Study Design and Setting

A quantitative, retrospective cohort study was conducted in Butha-Buthe and Mokhotlong, two districts in northern Lesotho. The two districts combined have 22 health facilities. Butha-Buthe has ten rural health centers, one missionary hospital, and one governmental hospital. Mokhotlong has nine rural health centers and one governmental hospital. With an estimated 250,000 residents, both districts are characterized by primarily rural surroundings. Most of these residents are subsistence farmers and mine workers, as well as domestic or construction workers who are employed in neighbouring South Africa. There has been a slight increase in adult HIV prevalence from 17.8% in 2016/17 to 18.8% in 2020 with12225active ART patients in Butha-Buthe and reduction from 26.1% in 2016/17 to 18.9% in 2020 with 10,784 active ART patients in Mokhotlong.⁵

Study Participants

The study population included all ART patients (age ≥15 years) registered in an established VL monitoring database with at least two consecutive high VL results between December 2015 and December 2019 from any of the 22 health facilities in Butha-Buthe and Mokhotlong districts.

Inclusion Criteria

All ART patients are more than 15 years of age in the VL monitoring database with at least two consecutive high VL results between December 2015 and December 2019 that have been receiving ART for at least 6 months and more.

Exclusion Criteria

All ART patients in the VL monitoring database entered before December 2015 and after December 2019, ART patients less than 15 years of age, on treatment for less than six months and have only one viral load result.

Data Collection Tools and Procedure

The viral load monitoring database is part of a prospective open cohort study started in November 2015 that includes individuals on ART who have received a viral load testing conducted at the laboratory based in Butha-Buthe Government Hospital. The Butha-Buthe and Mokhotlong districts now use this laboratory for testing. Trained laboratory technicians export the viral load results into the password-protected monitoring database. To ensure the accuracy of data, data clerks review each laboratory record from the Laboratory Information System (LIS), and health facilities are alerted if any information is missing or inconsistent.

Retrospective data of all eligible ART patients was extracted from the monitoring database into an Excel sheet format. The electronic data was stored and protected by a password, and no unauthorised persons accessed the data. All electronic records were backed-up and maintained for five years. Data was processed and cleaned after entry to ensure quality. Raw data and log files have been stored separately and backed-up using an external hard drive. All electronic data will be safely erased after the five-year data retention period. The appropriate authorities authorized all decisions regarding data dissemination.

Statistical Analysis

Data analysis was conducted using STATA 15.1 (Stata Corp. 2015. Stata Statistical Software: Release 15. StataCorp LP, College Station, Texas). Descriptive statistics were utilised to describe the socio-demographic, clinical and health-system-related characteristics of all study participants included in the study.

The association between virological failure and independent variables was investigated using bivariate and multivariate logistic regressions. Bivariate analysis was first conducted to identify potentially significant associations with virological failure. A multivariate logistic regression model analysis with a significance value of p < 0.05 was also done for all variables which were found to be statistically significant. Independent variables included gender and age and clinical factors including the year of first ART initiation, virological failure, baseline CD4 count, WHO staging at ART initiation, type of ART regimen at the start, previous ART treatment, year of HIV diagnosis, TB history, missed doses, pregnancy and breastfeeding.

Ethical Considerations

Informed consent was waived by the National Health Research and Ethics Committee of Lesotho (NHREC) for this retrospective study, as all the data were de-identified. The confidentiality of information obtained from each study participant was guaranteed by omitting names or any personal identifiers. Moreover, the collected data were kept safe throughout the whole process of the research work to limit data accessibility to a third party. The Biomedical Research Ethics Committee (BREC) of the University of KwaZulu-Natal, Durban (protocol reference number BREC/00003162/2021), and the NHREC (REF ID 08–945 2021), provided approval for this study’s ethical conduct. The study complied with the prescripts of the Declaration of Helsinki.

Results

Study Population

A total of 20,945 ART patients (age ≥15 years) who had at least two consecutive VL results between December 2015 and December 2019 from 22 health facilities in the Butha-Buthe and Mokhotlong districts were included in the study. Out of 20,945, 10.7% (n = 2243) had at least one unsuppressed VL. Of the 20,945 patients, 931 (4%) patients had two consecutive high VLs and 20,014 (96%) patients were virologically suppressed.

Socio-Demographic Profile

The age of the study population was centrally distributed with a mean age of 45 years (SD 13.7) and a median age of 44 years (IQR: 36–56 years). There were more females (almost twice the number) 66.6% (n = 13,939) than males 33.4% (n = 7000). Patients within 35 to 44 years age group constituted the highest proportion of the population 29.86% (n = 6254), followed by 45 to 54 years age group with 23.4% (n = 4902) of the population (Table 1). In participants without virological failure, there were twice as many females 66.5% (13,325) compared to males 33.4 (6683). The highest proportion age group of all the without virological failure patients is 35 to 44 years, 29.6% (n = 6254), followed by 45 to 54 years with 23.4% (n = 5949) participants.

Table 1 Frequency Table of Demographic and Clinical Profile of Adult HIV Patients Receiving Care in Butha-Buthe and Mokhotlong Districts, 2015–2019

Variables	Categories	No Virological Failure		Virological Failure		Study Population
		N	%	N	%	N	%
Gender	Female	13,325	67%	614	66%	13,939	67%
	Male	6683	33%	317	34%	7000	33%
Age group	15 to 24 years	1103	6%	144	15%	1247	0.01%
	25 to 34 years	3189	16%	145	16%	3334	0.02%
	35 to 44 years	5949	30%	305	33%	6254	0.03%
	45 to 54 years	4698	23%	204	22%	4902	0.02%
	55 to 64 years	3169	16%	94	10%	3263	0.02%
	65 to 74 years	1518	8%	29	3%	1547	0.01%
	75 + years	388	2%	10	1%	398	2%
WHO staging	Stage 1	527	3%	9	1%	536	3%
	Stage 2	436	2%	6	1%	442	2%
	Stage 3	317	2%	6	1%	323	2%
	Stage 4	24	0%	2	0%	26	0%
	Missing	18,710	93%	908	98%	19,618	94%
TB History	Yes	1067	5%	13	1%	1.08	0%
	No	242	1%	6	1%	248	1%
	Missing	18,705	93%	912	98%	19,617	94%
Breastfeeding	Yes	563	4.7%	38	6.2%	601	4.1%
	No	13,376	95.3%	576	93.8%	13,939	95.9%
Pregnant	Yes	237	1.7%	8	1.3%	245	1.7%
	No	13,702	98.3%	606	98.7%	14,308	98.3%
Missing medication doses	Yes	19,059	95%	877	94%	19,936	95%
	No	435	2%	23	2%	458	2%
	Missing	520	3%	31	3%	551	3%
Time on ART	Mean	67 months (SD 34.15)		83.6 months (SD:29.32)		69.6 months (SD:34.09)
	Median	64 (IQR: 42–102)		91 (IQR: 57–109)		65 (IQR: 43–102)
CD4 Count	Mean	360 (441.6)		356.1 (SD: 272.8)		357.4 (SD: 435.7)
	Median	297 (IQR: 162–479)		276.5 (IQR: 165–483.5)		293 (IQR: 159–477)

Among participants with virological failure, more than two-thirds, 66% (614) were females, compared to 34% (n = 317) males. The highest proportion age group of all the virological failure patients is 35 to 44 years, 32.8% (n = 305), followed by 45 to 54 years with 21.9% (n = 204) participants. The proportion of virological failure decreases with increased age group, with 10.1% (n = 94), 3.1% (n = 29) and 1.1% (n = 10) among 55 to 64 years, 65 to 74 years, and 75+ years, respectively. The mean age for patients with virological failure was 40 years (SD 13.7) and the ranged 15 years to 87 years. Clinical data for WHO staging and TB history was missing for 93.7% (n = 19,618), of patients.

The mean time on ART for patients with virological suppression was 69.6 months (SD 34.09), with a median time of 65 months (IQR: 42 months to 102 months) in comparison with the 83.6 months (SD 29.32), and a median time of 91 months (IQR: 57 months to 109 months) for patients with virological failure. CD4 count mean was 360.1 cells/mm³ (SD 441.6) with median of 297 copies (IQR 162 to 479 cells/mm³), with virological suppression in comparison to a mean CD4 count of 356.1 cells/mm³ (SD 272.8) with median of 293 copies (IQR 166 to 483.5 copies), amongst patients with virological failure (Table 1).

Factors Associated with Virological Failure

On bivariate analyses, time on ART > 65 months (AOR: 1.85 CI: 1.59–2.15), being on second-line ART regimen (UOR: 75.23 95% CI: 62.65–107.4) and breastfeeding (UOR: 1.46 95% CI: 1.04–2.06) showed statistically significant (p < 0.001). Patients that were between 15 years and 64 years showed significantly less likely odds of the experiencing virological failure compared to patients >65 years of age (Table 2).

Table 2 Bivariate and Multivariate Analysis Assessing Associations Between Independent Variables and Virological Failure in Butha-Buthe and Mokhotlong Districts from 2015 to 2019

Variables	Categories	Unadjusted OR	95% CI	P-value	Adjusted	95% CI	P-value
					OR
Gender	Males	1.03	0.90–1.18	0.682
	Females
First CD4	< 300
	≥300	1.34	0.18–10.14	0.18
Breastfeeding	Yes	1.46	1.04–2.06	0.02*	#	#	#
	No
Pregnant	Yes	0.74	0.363–1.500	0.4	#	#	#
	No
Time on ART	< 65 months
	≥ 65months	1.81	1.58–2.08	<0.001**	1.85	1.59–2.15	<0.001**
Missed doses	Yes	1.15	0.75–1.76	0.521	#	#	#
	No
TB History	Yes	0.49	0.18–1.31	0.154
	No
Who clinical stage	Stage 1	0.21	0.04–1.01	0.05	#	#	#
	Stage 2	0.12	0.03–0.86	0.03	#	#	#
	Stage 3	0.23	0.43–1.19	0.08	#	#	#
	Stage 4
Age groups	15–24	0.35	0.27–0.44	<0.001**	0.39	0.30–0.51	<0.001**
	25–34	0.39	0.32–0.48	<0.001**	0.4	0.32–0.50	<0.001**
	35–44	0.33	0.27–0.42	<0.001**	0.32	0.25–0.41	<0.001**
	45–54	0.23	0.17–0.30	<0.001**	0.22	0.16–0.29	<0.001**
	55–64	0.16	0.11–0.22	<0.001**	0.15	0.11–0.23	<0.001**
	≥65
ART	1st Line	1
Regimen	≥ 2nd Line	82.0	62.65–107.4	<0.001**	75.23	57.00–99.16	<0.001**

Notes: ^#Breastfeeding, missed doses, pregnancy, WHO clinical staging omitted because of collinearity. *p<0.01, **p<0.001.

Abbreviations: ART, active antiretroviral treatment; LePHIA, Lesotho household-based national survey; OR, odds ratio; PLHIV, people living with HIV; SSA, sub-Saharan Africa; VL, viral load; WHO, World Health Organization.

After multivariate analyses and adjusting for possible effects of confounding variables the time on ART > 65 months (AOR: 1.85 CI: 1.59–2.15), being on second-line ART regimen (AOR: 75.23 95% CI: 75.00–99.15) were significant (p < 0.001) associated with virological failure. Patients that were between 15 years and 64 years showed significantly less likely odds of the experiencing virological failure compared to patients >65 years of age (Table 2). WHO staging showed a collinearity effect on the variables and was removed from the final model. Pearson’s Chi-squared goodness of fit was applied to the final model that showed a Pearson chi2(16) = 25.86 and Prob > chi2 = 0.05 indicating a good fit for the model.

Discussion

The prevalence of virological failure was 4.0%. The result was far less than what was reported in the LePHIA 2020 where 8.5% of adults on ART had unsuppressed VL.⁵ The possible reason might be the methodological difference in the assessment of virological failure, the definition of virological failure and the study design which was a national household-based survey with a big sample size.⁵ In our study, we define virological failure as two consecutive unsuppressed VLs while in LePHIA, they only look at one-point unsuppressed VL, this could explain why our study has less virological failure prevalence.¹³ A higher prevalence of virological failure was reported in previous studies, with 17% reported in Cameroon, 10% in South Africa, 14.7% in Ethiopia, 41% in rural Gabon and 10% in Tanzania.^14–16 The two districts of Butha-Buthe and Mokhotlong benefited from the support of the non-government organization that provided patient adherence counselling, self-supportive management for patients and training for staff on identifying defaulters and patients with low viral load counts for intensive follow and better-informed management may have contributed to the relatively lower estimates in our study compared to the average estimate in other African countries.

The gender distribution of the study participants is in line with previous studies about ART coverage and outcomes in Southern Africa.¹⁷ This is consistent with a report from UNAIDS data which showed that in Lesotho, there were twice as females (65%) on ART compared to males (35%), and another cohort study in Tanzania focusing on the ART outcomes reported that there were 70% females compared to 30% males.¹⁷ This could be due to better health-seeking behaviour among women compared to men as women are more likely to present earlier at a health facility while men are usually late presenters with advanced HIV diseases at the time of presentation at the health facilities.¹⁸ Another explanation could be that since a decade ago, global and national ART-related policies and initiatives in Africa were focusing more on women than men.¹⁸ Previous reports showed that almost all African countries included initiatives focusing on women in their national AIDS strategies; however, only approximately 10% of countries have initiatives that effectively engaged men and boys in their national AIDS strategies.¹⁹

Factors Associated with Virological Failure

Patients on second-line treatment showed increased odds of virological failure. Findings from a systematic literature review of 33 studies with the overall 18,550 participants and 19,988.45 person-years (PYs) of follow-up showed the pooled second-line HIV virological failure rate was 15.0 per 100 PYs (95% CI: 13.0–18.0). It was slightly higher at 12–18 months of follow-up (19.0/100 PYs; 95% CI: 15.0–22.0).²⁰

The explanation for high odds with second-line ART or more in our study could be because those patients have a history of poor adherence to ART before and therefore could be easy for them to default to ART once again. In addition to other factors, the same systematic literature indicated that suboptimal adherence to second-line therapy (OR: 1.92; 95% CI: 1.28–2.86) was associated with second-line virological failure.²⁰

Also, since all patients in Lesotho are switched to second-line ART regimen based on virological failure definition of two consecutive high VLs not with drug resistance testing to which specific drugs the patients have developed resistance mutation on. In the absence of drug resistance testing, unnecessary regimen switches are common, resulting in increased treatment costs and loss of future options for treatment succession and putting the patient at increased risk for drug toxicity from the second-line regimen. Patients could be switched to the same class of drugs they have accumulated resistance mutation to, therefore causing drug resistance to the new drug switched on.

The findings from our study showing an increased odds of virological failure if the patient received ART for >65 months is consistent with reports from an institutional-based prospective cross-sectional study design in 2021 at a referral hospital in Western Ethiopia that reported increased odds for the duration of treatment of six years.²¹ The findings are similar to the cross-sectional study in Ethiopia that reported that patients on ART for 6–24 months were 52% less likely to develop virological failure compared to patients on ART for 72 months and more.²²

In China, a cross-sectional study among 351 participants finds that longer duration on ART was associated with virological failure, patients on ART for 55 years and more had an increased odds of virological failure (OR: 1.7, 95%< CI 0.8–3.8; ≥55 months) compared to 12 months or less.²³

The duration on ART and ART regimen interacts as it is more likely that patients on longer duration of treatment will receive >2nd line regimen of treatment. In the current study virological failure was assessed on the patient’s current ART regimen, they were taking when they were virally unsuppressed, not accounting for the previous history of ART regimen.

As ART duration increases, there is a possibility of missed doses, poor adherence, lost to follow-up and drug side effects increase as well. Besides, as the duration increases, patients may have acquired drug resistance mutation due to HIV error during the replication.^24,25 Therefore, high VL with the drug-resistant mutation was expected among ART patients with more months on treatment than with fewer months on ART.

Our findings show that patients at a younger age were significantly less likely to develop treatment failure compared to elderly patients >65 years of age. A cross-sectional study using routinely collected program data among 100,678 participants conducted in Uganda that young age is associated with virological failure compared to participants older than 35 years and the higher proportions of virological failure were found in children (29%) and adolescents (27%).²⁶

Another cross-sectional analysis (2006–2010) involving 17,044 HIV-infected adults in 14 clinical cohorts across the US and Canada has highlighted a link between young age and virological failure.²⁷ However, a study conducted in Northern Ethiopia reported that the patients who started second-line ART aged 45 years and above had a higher incidence of virological failure compared to patients who started aged 15 to 29 years.¹⁵ Peer pressure, stigma, discrimination, and lack of youth-friendly services at the health facilities might have negative effects on adherence to ART in younger persons and predispose them to virological failure.²⁸ In addition, engagement in risk behaviours such as alcohol, drugs and substance abuse decreases their chance of good treatment outcomes.²⁸

Among the study population, the average CD4 count was 357 cells/mm³ with an average of 360 cells/mm³ for virally suppressed patients and 356 cells/mm³ for patients with virological failure. Bivariate analysis, having a baseline CD4 count of 300 cells/mm³ and above was 42% less likely to develop virological failure compared to having a baseline CD4 count of fewer than 300 copies/mm³. The findings are supported by previous studies in China, Cameroon and Ethiopia also all reported an association of virological failure with baseline CD4 count less than 200.^29–31

In Cambodia, a ten years’ experience retrospective cohort analysis showed that a baseline CD4 count below 200 was associated with virological failure compared to those with a higher CD4 count of 200 and above.²⁹ The higher (threshold) cut-off CD4 count of 300 cells/mm³ in our study could be explained by that we used the median CD4 count for regression analysis while other studies used cut-off defined by WHO or national ART guidelines.

Other studies found a significant association with a lower baseline CD4 count of 50 copies/mL or below.^32,33 A similar positive association between lower CD4 count and virological failure was observed observational study that included 5 Asian countries which showed that lower CD4 count is significantly associated with virological failure regardless of whether is at baseline or during ART.³² The findings could be that people with lower CD4 at baseline are more likely to have bad health-seeking and adherence behaviour or that they may be at higher risk of acquiring resistant mutation. Another explanation might be explained by the inverse relationship between CD4 count and VL, as VL increases (unsuppressed) CD4 count decreases. Also, the different cut-off (threshold of CD4 count) from WHO guidelines especially in low-income countries that mainly rely on WHO recommendations.

Limitations

In this study, we used retrospective secondary data that missed some essential variables which might have an impact on outcomes of virological failure and associated factors, such as patient factors (marital status, employment, educational status, transport cost, social support, distance to the health facility) and clinical factors (adherence data, year of HIV diagnosis, opportunistic infections, depression, drug resistance testing, pill count), that were not recorded. Children below 15 years were excluded from the study analysis.

Secondly, there were missing data on some of the variables. Variables such as WHO clinical staging, TB history, missed doses, and pregnancy among others were incomplete and participants who did not have data on such important variables were excluded from the analysis. Some of the variables proposed in our conceptual framework were not available. The time the patients start failing the first-line ART regimen and the time the patients switch to the second-line ART regimen after the first-line failure was not included in the study.

Conclusion

The prevalence of virological failure in our study is lower than reported in other SSA countries. ART regimen (second- and third-line regimen) was significantly associated with virological failure in our study population. Virological failure. In order to mitigate the risk for virological failure, it is important to perform targeted clinical assessments and examinations at every ART clinic visit to identify early clinical signs or symptoms of virological failure. In addition, it is important that regular education sessions about the risk of virological failure should be provided at each clinic attendance. Furthermore, healthcare providers should be continuously updated about the risk and guidelines for virological failure in patients on ART. Prior to initiating patients on second/third line treatment, it is important that resistance testing is conducted to make sure the patient is switched to approximate drugs.

Disclosure

The authors report no conflicts of interest in this work.

Acknowledgment

Ozayr Mahomed’s current address is Dasman Diabetes Institute, Kuwait City, Kuwait.