Anti-retroviral therapy after “Treat All” in Harare, Zimbabwe: What are the changes in uptake, time to initiation and retention?

Study design and population

For ART uptake, we used an ecological design involving aggregate secondary programme data and all PLHIV newly diagnosed before (2014 to June 2016) and during “Treat All” (July 2016 to 2018) in Harare were the study population.

For time to ART initiation and retention, we used a cohort design involving patient wise secondary programme data. We included all PLHIV newly initiated on ART from 50 electronic patient management system (ePMS) sites in Harare before (April–June 2015) and during “Treat All” (April–June 2017).

Study setting

General setting. Harare province constitutes 16.3% of the population in Zimbabwe¹¹, with an estimated 0.2 million PLHIV, the highest among all the provinces⁸. It has the highest number of patients active on ART, with 77 public ART sites providing HIV diagnosis and treatment. As on October 2018, the 50 ePMS sites constituted 52% of all people on ART in Harare province.

ART initiation before “Treat All”. Prior to “Treat All”, PLHIV were initiated on ART based on a CD4 eligibility criteria of <500 cells/mm³ (with priority given to those <300 cells/mm³ OR WHO clinical stage 3 or 4). Additionally, pregnant and/or breast feeding women, sero-discordant couples, Hepatitis B virus co-infection, people diagnosed with tuberculosis (TB) and children ≤5 years were also eligible irrespective of CD4 count.

Baseline investigations at primary level of care included urine dipstick (glucose, protein), haemoglobin, CD4 count for immunologic staging, cryptococcal antigen screen for adults with CD4 count <100 cells/mm³, screen for pregnancy, syphilis if 12 years or older and hepatitis B infection¹². Other investigations included full blood count, creatinine and hepatitis C serology at secondary or tertiary levels of care. PLHIV were screened for active TB and other Opportunistic Infections (OIs)¹². If active TB was diagnosed, ART was initiated within 2–8 weeks of initiation of anti-TB treatment and within two weeks for advanced TB disease.

Psychosocial criteria for ART initiation, also included completion of prescribed counselling sessions and an assessment of adherence to cotrimoxazole preventive therapy (CPT) in the past 3 months. Adherence to CPT was used to assess the likelihood that the patient would adhere to ART. Patients were followed up monthly initially and then every three months. Viral load testing targeted those suspected of HIV treatment failure¹³. A patient with confirmed virologic, immunologic or clinical failure were switched to second line ART¹². Data were routinely recorded in the ART register, patient OI/ART care booklet. The patient level data was also routinely captured electronically in the 50 ePMS sites.

If a patient officially transfers-out to another ART clinic, they are issued with a transfer-out letter for presentation at the receiving ART clinic and they maintain their ART number. In other instances, patients may unofficially transfer out to another health facility without being assigned a transfer-out letter and are therefore declared lost to follow-up if they exceed 90 days after their last scheduled clinic or drug pick-up visit and all phone-call or physical follow-ups attempts by community health workers to trace them back to care have been futile. The patients will often present at the transfer-in facility with a patient-held ART booklet which indicates their previous medical history and therefore continue receiving ART care whilst also maintaining their ART number. Alternatively, if no evidence of previous treatment is provided, they are offered an HIV test and subsequently assigned a new ART number and treated as new ART client

Changes in ART initiation and further management during “Treat All”. All PLHIV are eligible for ART regardless of CD4 count or WHO clinical staging¹⁰ although baseline CD4 monitoring is still important for determining the degree of immune suppression of a patient in order to inform ‘differentiated care’. Additional changes in the “Treat All” period included an emphasis for health workers to provide adequate counselling and start ART within a week with exception of pregnant and breast-feeding women who were to be started on ART on the same day of HIV diagnosis. However, for those patients who are not ready yet to start ART, they should receive on-going counselling and support. PLHIV are monitored for viral load at six months after starting ART, 12 months then annually thereafter if stable¹².

Data variables and sources of data

For ART uptake, we extracted quarterly aggregate number of new HIV diagnoses and new ART initiations from the District Health Information System 2 (DHIS 2). For time to ART initiation and retention, the source of patient level data was the ePMS and included OI/ART number; ART site; date of HIV diagnosis; date of ART initiation; date of birth; baseline characteristics and outcome at three, six and 12 months - alive and on treatment, death, loss to follow up, stopped ART, transferred out; and date of ART outcome. Operational definition of outcomes has been depicted in Table 1.

Analysis and statistics

For ART uptake, we calculated quarterly proportions of newly diagnosed PLHIV initiated on ART (Microsoft Excel 2010, Microsoft, Redmond, WA, USA) and presented them using bar diagram and trend lines.

We summarized time to ART initiation after diagnosis using median (interquartile range - IQR) and compared it before and during “Treat All” using Mann Whitney U test. We also used frequency and proportions to summarize time to ART (same day, 2–7 days, 8–14, 15–30 days, 31–90 days, 91–180 days, >180 days] and compared it before and during “Treat All” using z test for proportions. Baseline characteristics and cumulative retention in care were also compared using z test for proportions (STATA - version 12.1, copyright 1985–2011 Stata Corp LP USA).

Ethics

We obtained ethics approval from the Union Ethics Advisory Group (EAG), Paris, France (EAG number: 47/19, 29 April 2019) and the Medical Research Council of Zimbabwe (MRCZ), Harare (MRCZ/E/245, 19 August 2019). As this study involved review of existing programme records, we sought and obtained waiver of written informed consent from the ethics committees. Secondary data were extracted after obtaining administrative approval from the concerned authorities.

ART uptake

A total of 84,776 people were diagnosed with HIV before (2014 to June 2016) and 82,672 during “Treat All” (July 2016 to 2018). ART uptake increased from 65% (n=4619) by the end of quarter one, 2014 to 85% (n=5152) by the end of quarter four, 2018. Starting quarter three, 2016 (implementation of “Treat All”), there was an increasing trend in the new ART initiations, as well as the ART uptake up to quarter two, 2017. Between quarter three, 2017 and quarter four, 2018, there was an increasing trend in ART uptake, which peaked to 85% (n=5152) (Figure 1). However, during this period, the absolute number of HIV diagnoses as well as the absolute new ART initiations reduced.

Figure 1. Trends^# in quarterly ART uptake^ among newly diagnosed PLHIV before (January 2014–June 2016) and during (July 2016–December 2018) “Treat All” *, Harare, Zimbabwe.

PLHIV: People Living with Human Immunodeficiency Virus; ART: Antiretroviral therapy ^aggregate numbers for each quarter were extracted to calculate ART uptake, source of data is district health information system (DHIS-2) *” Treat All” means all individuals with confirmed HIV diagnosis are eligible for ART irrespective of WHO clinical stage or CD4 count. ^#During 2014, the CD4 count eligibility criteria was raised from <350 to <500 cells/mm³³. As more people in pre-ART care were eligible for ART, there was an increase in new ART initiations which resulted in corresponding increase in ART uptake. Similarly, there was an increase in new ART initiations which resulted in corresponding increase in ART uptake after “Treat All”.

Baseline characteristics among PLHIV newly initiated on ART

A total of 2289 PLHIV were newly initiated on ART before (April-June 2015) and 1682 were newly initiated during “Treat all” (April-June 2017). The median age (in years) for the two groups was similar, 31 (IQR: 27, 41). Gender distribution before and during “Treat all” was also similar (women: 58.6% vs. 58.3% respectively). The proportion of people in early stages of disease (WHO clinical stage I or II) was significantly higher during “Treat all” (73.2% vs. 55.6%, p<0.001).

Time to ART initiation from diagnosis

We were not able to calculate the time interval for 41% of people because of missing dates. Of those with dates available, the median time to ART initiation from diagnosis was significantly lower during “Treat All” when compared to before “Treat all” (31 vs. 88 days, p<0.001). ART initiation on the same day (19.3% vs. 4.9%, p=<0.001) and within 14 days (25.5% vs 12.5%, p<0.001) was significantly higher during “Treat All” (Table 2).

ART retention

Retention at three, six and 12 months was consistently lower during “Treat All” compared to before “Treat All”. It was significantly lower at six months (74.9% vs.78.1% p=0.022) (Table 3).

Underlying data

Figshare: Matare T et study 2020 ART uptake, initiation delay and retention data, https://doi.org/10.6084/m9.figshare.c.4944399²⁰.

This project contains the following underlying data:

Data are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).