*2.2. Setting*

2.2.1. General Setting: Zimbabwe and Harare

Zimbabwe is a low-income country in southern Africa with an estimated population of 14.6 million in 2019 and a gross national income per capita of USD 1390 [17,18]. About 70% of the population live below the poverty line. Zimbabwe is among the top 14 countries globally with a triple burden of TB, HIV and multidrug-resistant TB [19].

Harare is the capital city with an estimated population of 1.5 million [20]. The current study took place in Harare for two main reasons. The majority of cases of COVID-19 came from this area at the onset of the pandemic, and travel around the country was extremely difficult due to quarantine and prohibited travel outside of the city during the initial lockdown. Harare city consists of 8 districts, that include 46 public health facilities, of which 44 are under the Harare City Health Department. These provide general health services integrated with TB and HIV services whilst the other two are governmen<sup>t</sup> central hospitals which provide specialized health services. Of the 44 public health facilities under the Harare City Health Department, 13 are polyclinics which additionally provide maternity services, 29 are satellite clinics and 2 are infectious disease hospitals (of which one became reserved as the city's COVID-19 isolation center). Through stratified nonproportional sampling from each district, ten health facilities (nine polyclinics and one satellite clinic) were selected from a list of high-volume health facilities based on more than 1000 patients receiving life-long ART as a proxy for the volume of presumptive TB patients seen per year. The established staff who were already working in these sites delivering general health services and TB and HIV services assisted with the monthly collection of data.

#### 2.2.2. TB and HIV Services

The diagnosis and treatment of TB and HIV/AIDS in Zimbabwe are the responsibility of the NTP and the NAP, respectively, under the Ministry of Health and Child Care (MO-HCC). People with symptoms suggestive of TB (typically, cough, fever, weight loss and night sweats) are classified as having presumptive TB when they attend a health facility. They are recorded as such in the presumptive TB register along with their demographic details. In the Harare city clinics, sputum samples are collected and sent to an onsite laboratory at each polyclinic, except satellite clinics that submit specimens to a laboratory at the nearest polyclinic. In the laboratories, patient details and sputum results are entered in the laboratory register. Investigations are carried out according to national and international guidelines [21,22], using the Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) and/or sputum smear microscopy to establish a bacteriologically confirmed diagnosis of pulmonary TB (PTB), and results are sent back for patient tracking.

Those patients with a negative sputum result but who still have TB-related symptoms are referred to see a doctor at either of the two nearest infectious disease hospitals where clinical assessments, radiography and other circumstantial evidence are used to establish a diagnosis of clinically diagnosed PTB or extrapulmonary TB (EPTB). These patients are started on TB treatment before referral back to their initial health facility for registration and continuation of TB treatment. Patients with diagnosed TB are registered in the health facility Directly Observed Treatment (DOT) register and started on anti-TB treatment in accordance with national and international guidelines [21,22]. In the selected health facilities in Harare, patients with drug-susceptible TB (DS-TB) are treated and monitored with the standard 6-month regimens, while those with the drug-resistant disease are treated and monitored with MDR-TB regimens. Patients with drug-resistant TB were not included in this study. Treatment outcomes are monitored, recorded and reported according to international guidelines [23].

HIV testing takes place in public health facilities and is routinely offered to anyone attending for care, including TB patients, according to national and international guidelines [24–26]. HIV testing is carried out using rapid testing algorithms in line with WHO guidance, and test results are entered in the HIV Testing Services (HTS) register that is placed at all health service delivery points. Once patients are diagnosed positive for HIV, they are retested for verification of HIV diagnosis and, if confirmed HIV-positive, they are then prepared and counseled for ART and referred for immediate start of ART regardless of WHO clinical stage or CD4 cell count. Administration of an HIV screening tool for HIV risk assessment before providing a rapid HIV test and use of HIV self-testing are measures that have been scaled up recently to improve the HIV positivity yield.

There is generally good quality data capture and reporting for TB and HIV/AIDS at all levels due to regular supervision by national program supervisors.

2.2.3. Data Monitoring, Recording and Reporting for the Study in Health Facilities in Harare

Data were routinely collected daily by front-line health workers. They provided services in each of the ten health facilities in Harare using the standard MOHCC monitoring tools (presumptive TB register, sputum laboratory register, TB patient register and HTS register), most of which were paper-based. One to two weeks after the end of each month, the project country coordinator (KCT—who was appointed specifically for the study) visited each site along with his team of trained data collectors. They collated the individual data on TB and HIV variables for the previous month into monthly aggregate data, which they then entered into a proforma developed using an EpiCollect5 application (https://five.epicollect.net, accessed on 29 May 2021).

For TB treatment outcomes, the monthly cohorts of patients enrolled onto treatment eight months previously were used—this allowed for six months of treatment to be completed and a further two months for outcomes to be validated and recorded in the registers. For example, the October 2020 TB treatment outcome data were obtained for TB patients enrolled and started on treatment in February 2020. This allowed for clear separation of treatment cohorts in the pre-COVID-19 and COVID-19 periods.

National data on COVID-19 cases and deaths reported to WHO on the last day of the month were obtained from WHO situation and epidemiological reports [1].

When the prospective monthly data were collected, a schedule and the same procedures were used to collect retrospective data. For each month of the COVID-19 period (March 2020 to February 2021), data were collected on TB and HIV parameters for a matching period one year before the COVID-19 period (March 2019 to February 2020).

Once all prospective and retrospective data for the month had been entered into EpiCollect5, they were checked and validated by both the project country coordinator and the overall project monitoring and evaluation officer (PT) based at The Union. Data were then presented in a monthly report as a series of figures and tables and narrative to the directors of the NTP and NAP and to all other relevant stakeholders involved in the project. Key policy or practice changes made at the local health facility or at the national level during that month to explain and/or counteract the effects of COVID-19 on TB and HIV parameters were recorded in a narrative table within the report. These monthly reports were always sent and received by the national program staff within four weeks of closure of that month to enable timely surveillance and possible action.

### *2.3. Study Population*

The study population included all patients presenting to TB services with presumptive TB, all TB patients registered for DS-TB treatment and all persons tested for HIV between March 2019 and February 2021; March 2020 to February 2021 was the COVID-19 period, and March 2019 to February 2020 was the pre-COVID-19 period. We also included TB patients registered for treatment eight months prior to the study period to assess treatment outcomes.

#### *2.4. Data Variables, Sources of Data and Timing of Data Collection*

Data variables for TB included aggregate numbers of patients: with presumptive PTB, stratified by male and female, adults ( ≥15 years) and children (<15 years); who were diagnosed with bacteriologically positive PTB by either smear microscopy and/or Xpert MTB/RIF; with registered TB, stratified by bacteriologically confirmed PTB, clinically diagnosed PTB and EPTB; and with registered TB, who were newly tested for HIV in that month after being diagnosed with TB—this excluded patients who already knew they were HIV-positive or had recently been diagnosed HIV-negative. Standardized TB treatment outcomes of those patients enrolled for treatment eight months previously were collected and included—treatment success (a combination of those cured and those who completed treatment with no sputum smear examination), lost to follow-up (LTFU), died, failed treatment or not evaluated [23]. LTFU refers to a TB patient who did not start treatment or whose treatment was interrupted for two consecutive months or more. Not evaluated is an outcome given to those who transfer from one facility to another and for whom the final treatment outcome is not recorded and also to those whose outcome is not recorded and unknown to the reporting unit.

Data variables for HIV included: persons who were HIV tested at the health facilities, stratified by male and female, adults ( ≥15 years) and children (<15 years); persons diagnosed HIV-positive; and HIV-positive persons referred to ART services.

Sources of data were the presumptive TB register, the sputum laboratory register, the TB patient register, and the HTS register. Prospective and retrospective data for the study were collected between June 2020 and March 2021.

#### *2.5. Analysis and Statistics*

Aggregate data were entered in EpiCollect5, where they were checked and validated in-country by the country coordinator and by The Union's monitoring and evaluation officer. Data were presented as frequencies and proportions, and comparisons were made between the COVID-19 period and the pre-COVID-19 period. The percentage decline in numbers during each month of the COVID-19 period was calculated relative to the numbers during the same month of the pre-COVID-19 period. The relative percentage differences observed between the first 6 months of COVID-19 (March to August 2020) and the second 6 months of COVID-19 (September 2020 to February 2021) were also calculated.
