In this study, we aimed to assess the outcomes of adolescents and adults on second-line ART. We observed virologic suppression increasing over time from 44% six months after switching to second-line ART to 47% at 24 months and 58% at 36 months. Studies have shown that viral suppression is commonly achieved within 6 months after using effective ART and maintain undetectable viral load thereafter [15,16]. Fifty-eight percent of viral suppression in this study is below the 2020 UNAIDS third target . Contrary to our study, a recent study from South Africa a country with the largest HIV epidemic in the world, found that HIV-infected patients initiated on the second line with > 90% adherence achieved moderate to high rate of viral suppression; 73% at 6 months which later increased to over 97% at 24 months . In India, 78% of patients on the second line achieved viral suppression at 12 months . Other areas like Cambodia have reported viral suppression in 85.7% at 24 weeks among patients on the second line  and Rwanda 83% . The difference found in our study could be explained by the delay to initiate the second line after the failure of the first line, which was a prevalent practice in the years before scale-up of viral load monitoring in 2014, and this demonstrates the challenge of using a clinical and immunologic status for ART failure [21, 22]. Second-line comprises of Protease Inhibitor (PI) based ART regimen which is more effective than the Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) used in first-line [23, 24]. The high genetic barrier to resistance of the PI drugs provides room for improvement after the failure of first-line . Enhanced adherence intervention was introduced along with HIV viral load monitoring has played a significant role to improve virologic outcomes in patients who have high viral loads >1000copies/ml and adherence issues [18, 19]. WHO guidelines recommend that patients with HVL>1000copies/ml be subjected to an enhanced adherence support intervention, after which a second viral load test should be performed prior to the decision on confirmed virologic failure and the subsequent ARV regimen [26,27].
We found increasing age from the age group 25-39 years and 40-59 years as a predictor of viral suppression (viral load < 50copies/ml) relatively similar to findings in the USA that older age (18-39 years) was significantly associated with viral suppression, as they sustained higher ART adherence as they get older . Similarly, other studies have reported that increasing age reduced the odds of non-viral suppression .
Retention to HIV care is key to a successful ART programme. Our study found that six months after switching to second-line ART more than 80% of patients were retained and this was maintained between 12 and 36 months. In addition, increasing age from younger age between 25 and 39 years to those aged 40-59 years were more likely to be retained to care, similar to a study in Kenya . This is impressive and should be maintained throughout the cascade of HIV care because retention has been considered as a predictor of viral suppression Our findings are similar to a recent national programme analysis of routinely collected data in Tanzania, which reported the overall rate of retention after enrollment in HIV care was 80.9% at 12 . In this report, it appeared that the highest level of retention was observed in young adults PLHIV aged between 35 and 49 years and those with lower and higher age groups had decreased retention . However, reported findings in South Africa and Uganda found that older age ≥ 45years was protective of loss to follow up [32, 33]. This difference could be attributed to a possibility of the older PLHV have multiple co-morbidities which warrants them to maintain clinic visits .
Additionally, we found that male gender was a predictor of retention while in previous studies, men enrolled in HIV care and on treatment were found to have worse retention than females [34-36]. In East Africa, a qualitative study reported that men had a desire of maintaining improved health and this was a motivating factor for them to remain engaged in care . Also, African men receive more support from their spouses than females and this underscores the importance of family support to maintain retention to care . Furthermore, we found that good adherence increased the likelihood of retention to care similar to other studies  and retention has been reported to facilitate ART adherence . The younger adults 25 years and above up plus those up to 59 years were found to be more retained to care. In our setting these (15-49 years) are the most affected group with HIV infection  therefore, retaining them to care is key for improving ART adherence hence good clinical outcomes and gain the benefit of reducing HIV transmission to their peers.
On the other hand, PLHIV who presented with WHO clinical stage III & IV at the time of switching to the second line were less likely to be retained to care similar to other studies reporting poor retention among sicker patients  who may be too sick to attend to HIV clinics or may have died and the death not reported at the attending clinic. Some patients with advanced HIV disease are more likely to seek alternative traditional health practitioners and leave medical care in an African setting [39, 40], some may be returned to their domicile places waiting to die there as it was found in West Africa .
Furthermore, patients who experienced an increase in body mass index, using Isoniazid prevention therapy (IPT), history of tuberculosis treatment and having a higher CD4 cell count were associated with less retention to care. This could be due to the fact that when PLHIV gain weight and achieve higher CD4 cell counts it translates to getting healthier. Thus weight gain gives a thought of being a marker of ART success and these individuals may not comply better with their clinic appointments than those who are underweight who will most likely keep close follow up of their care desiring for weight gain . Likewise, there are reports that feeling better, pill burden, and treatment fatigue are some individual risk factors for LTFU . Isoniazid Preventive Therapy (IPT) is an evidence-based intervention with the proven effectiveness of reducing the risk of TB in PLHIV by 33%–62% . Despite this evidence, the integration of IPT services has been sub-optimal due to reasons of pill burden to PLHIV and fear of side effects among the patient and also rumors and misconceptions about IPT among the HIV–infected patients .
In this study, we observed that retention was increasing over time and patients who were switched to second-line in the recent years from 2015 had a higher proportion of patients retained to care and achieved viral suppression. This can also be explained by the introduction of tracking interventions introduced in recent years underscoring the strategies to prevent loss to follow up. Also, ARV regimens that were introduced in recent years have enhanced drug efficacy and reduced side effects, promoting more optimal treatment response.
Therefore, retention in care is important for all HIV-infected patients and central to achieving optimal virologic outcomes emphasizing that viral suppression is more strongly associated with retention in care . Despite that viral load is the preferred way to monitor treatment efficacy because of the poor accuracy of CD4 monitoring in predicting viral suppression , less retention among patients with higher CD4 cell counts should be of concern among clinicians regarding the delay in detecting unsuppressed viral load among people failing second-line ART rendering a chance to an accumulation of drug resistance and increased risk of mortality and morbidity . Patients with higher CD4 cell counts are most likely to be asymptomatic and thus less motivated to be in care.
Our study limitation involved assessing variables that were available in the clinic data from routine care, which could be faced with incomplete and missing variables. However, it could be assumed that this happens randomly within our patients and thus did not introduce a systematic bias in the results.
Low coverage of viral load testing especially in early years (2012-2014), could lead to missing prior measurements among patients switched to second ART in early years, however, we controlled for calendar years to account for some of the facility practices that were not measured and not modeled in the regression. We only included patients in urban health facilities, this could represent different types of patients and facility practices when compared to rural ones and could limit generalization of the results.
In conclusion, we found a low rate of viral suppression (<50copies/ml) about 58% at 36 months after switching to second-line ART. This suggests that earlier second line initiation or switching before HIV disease progresses to an advanced level is paramount to improve treatment outcomes. In addition, more than 87% of individuals were retained in care at 6, 12, 24 and 36 months after switch. Male gender, having younger age (25-39years) and good adherence > 90% were predictors of retention. However, WHO stage III-IV, using IPT and higher CD4 cell count were associated with less retention. Therefore, improving viral suppression after switching to second-line requires stringent HIV viral load monitoring especially for adolescents to improve viral suppression and maximize the durability of the second-line regimens.