Children and adolescents on anti-retroviral therapy in Bulawayo, Zimbabwe: How many are virally suppressed by month six?

Background: Zimbabwe is one of the countries in sub-Saharan Africa disproportionately affected by human immunodeficiency virus. In the “treat all” era, we assessed the gaps in routine viral load (VL) monitoring at six months for children (0-9 years) and adolescents (10-19 years) newly initiated on anti-retroviral therapy (ART) from January 2017 to September 2018 at a large tertiary hospital in Bulawayo. Methods: In this cohort study using secondary data, we considered first VL done within six to nine months of starting therapy as ‘undergoing VL test at six months’. We classified repeat VL≥1000 copies/ml despite enhanced adherence counselling as virally unsuppressed. Results: Of 295 patients initiated on ART, 196 (66%) were children and 99 (34%) adolescents. A total 244 (83%) underwent VL test at six months, with 161 (54%) virally suppressed, 52 (18%) unsuppressed and 82 (28%) with unknown status (due to losses in the cascade). Switch to second line was seen in 35% (18/52). When compared to children, adolescents were less likely to undergo a VL test at six months (73% versus 88%, p=0.002) and more likely to have an unknown VL status (40% versus 22%, p=0.001). Conclusion: At six months of ART, viral suppression was low and losses in the cascade high.


Introduction
In 2014, the Joint United Nations Programme HIV/AIDS (UNAIDS) announced ambitious new global 90-90-90 fast-track HIV targets for 2020 1 . These targets were further supported by the 2016 "treat-all" WHO recommendations 2 . With the expansion of anti-retroviral treatment (ART) coverage, investments in the global response are shifting towards sustained viral suppression for improved survival and epidemic control. This is in the context of scaling up viral load (VL) monitoring to ensure 90% of people in care are virally suppressed (VL<1000 copies per ml) 3 . Globally in 2018, only 918 000 (54%) children aged 0-14 years living with HIV received ART 4 . HIV is among the top 10 leading causes of death among adolescents, a period where sustained adherence is particularly challenging, the only age group where deaths from HIV has not decreased 5 .
Zimbabwe is disproportionately affected by HIV. In 2017, 1.4 million people were living with HIV, with 5.8% being children 0-14 years 6 . An estimated 15% on ART have high VL 7 . The national ART guidelines recommend routine VL monitoring at six and 12 months, and then annually if stable on ART 8 . The extent to which routine VL monitoring is being implemented specifically for children and adolescents in the "treat-all" era has not been explored in Zimbabwe. We therefore assessed the gaps in routine VL monitoring at six months for children (0-9 years) and adolescents (10-19 years) initiated on ART at a large tertiary hospital in Bulawayo, Zimbabwe.

Study design
We conducted a cohort study involving secondary data.

Mpilo Opportunistic Infections (OI) Clinic is within Mpilo
Central Hospital in Bulawayo (the second largest city in Zimbabwe). It is a tertiary facility, managing complicated referrals, including patients on second and third line treatment. VL testing is offered as per national guidelines at the hospital HIV laboratory, adjacent to the clinic. Patient data are routinely entered in the electronic point of care database, ART register and patient care booklet 8 .

Study population
We included all children (0-9 years) and adolescents (10-19 years) newly initiated on first line ART at Mpilo OI Clinic between January 2017 and September 2018.

Data extraction and analysis
We extracted anonymized patient data from electronic patient and laboratory databases, analyzed using STATA (version12.1 STATA Corp., College Station, TX, USA). If data were missing in electronic databases, we referred to paper-based registers and booklets. We defined low CD4 count as follows: CD4 count ≤350 cells/mm 3 for children and adolescents >5 years, and CD4% <25% of total lymphocytes for children <5years 8 . We defined 'undergoing VL testing at six months' as those with first VL tests done within six to nine months of starting ART. Comparisons were made between children and adolescents using chi squared test.

Ethics
We received ethics approval from Medical Research Council of Zimbabwe (MRCZ E/248), The Union Ethics Advisory Group, Paris, France (EAG 52/19) and the Mpilo Hospital Ethics Board. As the study involved review of secondary data, the ethics committee(s) waived the need for written informed consent.

Discussion
This is one of the first studies from Zimbabwe attempting to assess the extent to which routine VL monitoring at six months is being implemented, specifically for children and adolescents in the "treat-all" era.
Overall, one in five of those initiated on ART were virally unsuppressed at six months. The true estimate could be higher considering viral suppression was unknown for one-third of children. High unsuppressed VL and the observed attrition along the care cascade, undermines the last '90' of the UNAIDS 90-90-90 targets in this special sub-population 1 . In this study, adolescents were more likely to be lost in the cascade compared to children, calling for focussed interventions for this sub-group. This is inspite of a comprehensive adolescent ART  *repeat VL≥1000 copies per ml despite enhanced adherence counseling; **VL<1000 at six months or after repeat VL testing (post enhanced adherence counseling); ***not fitting into any of the above two categories, represents children or adolescents that were lost at any point in the cascade.
program at the clinic, and suggests a reversal of gains made earlier in the progarm 9 .
Compared to findings in Harare, where two-thirds of those virally unsuppressed were switched to second line ART, only one-third were switched in our study 10 . Adherence to national ART guidelines should be an important priority focus in routine clinical mentorship 11 .
Four in five underwent VL test by six months and EAC in our study, consistent with findings in Harare 10 . However, we found high proportion with VL≥1000 copies/ml at first and repeat testing. In Swaziland, children and adolescents were more likely to have high VLs and the least likely to achieve viral suppression. This calls for ART treatment support to address adherence problems of children and adolescents 12 . The benefits of publishing with F1000Research: Your article is published within days, with no editorial bias You can publish traditional articles, null/negative results, case reports, data notes and more The peer review process is transparent and collaborative Your article is indexed in PubMed after passing peer review Dedicated customer support at every stage For pre-submission enquiries, contact research@f1000.com