Table 2 Components of same-day ART initiation in the VIBRA trial

Medical history

The study nurse assesses the patient’s medical history using a checklist; if necessary the nurse may refer the patient to a health facilty and may choose not to initiate same-day ART. In case of doubt, the nurse will contact the study physician

See checklist in Additional file 1 (eForm title “Medical history”)

Physical examination

The study nurse conducts a structured physical examination using a checklist; if necessary the nurse may refer the patient to a health facilty and may choose not to initiate same-day ART. In case of doubt, the nurse will contact the study physician

See checklist in Additional file 1 (eForm title “Physical exam”)

WHO stage

The study nurse assigns a clinical WHO stage according to the physical examination and medical history

CD4 measurement

The study team performs a point-of-care CD4 count, using PIMA Alere™ (a finger-prick test), which gives results within 20 min.

 ▪ If CD4 count < 350 cells/mcL: co-trimoxazole prophylaxis, 960 mg once daily orally, 1 tablet

  ◦ If participant < 14 years: 1/2 tablet once daily orally

 ▪ If CD4 count < 200 cells/mcL: cryptococcal antigen (CrAg) point-of-care measurement (lateral flow assay, IMMY©)

  ◦ If CrAg positive: immediate referral to a nearby district hospital by the study team and no same-day ART initiation

Although baseline CD4 counts are no longer used according to national guidelines to establish ART eligibility, the baseline CD4 count remains a strong indicator of early outcomes on ART and is, therefore, (a) an important variable for the study analysis and (b) an important clinical monitoring measurement for the prevention of opportunistic infections

The national guidelines suggest screening for CrAg only if CD4 count < 100 cells/mcL. However, data are scarce, so we will extend screening to those with CD4 count < 200 cells/mcL

For CrAg-positive patients, preventive or therapeutic antifungal treatment is indicated and a lumbar puncture is required. Thus, referral to the hospital is needed. Due to evidence that early ART initiation should be avoided if there is cryptococcal meningitis, same-day ART will not be initiated in CrAg-positive individuals until cryptococcal meningitis has been excluded

Creatinine measurement

The study team performs a point-of-care creatinine measurement, using StatSensor Creat™ Nova™ Biomedical (finger-prick test), which gives results within 2 min.

 • If estimated creatinine glomerular filtration rate according to the Cockroft–Gault equation < 50 mL/min: substitution of tenofovir disoproxil fumarate (TDF) with abacavir or zidovudine depending on the hemoglobin result

 • If estimated creatinine glomerular < 30 mL/min: the nurse may refer the patient to a health facility and may choose not to initiate same-day ART

According to national guidelines, a baseline creatinine measurement is needed before initiating standard first-line ART including TDF

Hemoglobin measurement

The study nurse performs a point-of-care hemoglobin measurement, using Hemocue^TM, HB301 (a finger-prick test), which gives results within 2 min.

 • If hemoglobin < 8 g/dL: zidovudine is contraindicated and the nurse may refer the patient to a health facility and may choose not to initiate same-day ART

According to national guidelines, hemoglobin must be measured before initiating an ART regimen containing zidovudine

Adherence counseling and education session

The study nurse conducts a structured education and adherence session, which is delivered using a leaflet, one-on-one, in approximately 5–10 min.

A condensed version of the education and counseling typically provided over the course of the former pre-ART visits was developed for and successfully tested in the previous trial (CASCADE trial)

Readiness assessment

Before dispensing ART, the study nurse will confirm the patient’s readiness and will answer all remaining questions, using a checklist

 • If the patient is not ready, they are referred to a health facility and same-day ART is not initiated

See checklist in Additional file 1 (eForm title “Readiness”)

Dispensing of ART

The study nurse prescribes a 1-month supply of the standard first-line ART according to national guidelines: TDF/lamivudine/efavirenz as a fixed-dose combination, once daily

 • If TDF is contraindicated, it is substituted with abacavir or zidovudine depending on the hemoglobin level

 • If the patient has an uncontrolled mental disease (e.g., active psychosis), they are referred to a health facility and same-day ART is not initiated

 • Depending on CD4 count, additionally 1 month’s supply of co-trimoxazole will be dispensed

The study nurses, like other qualified nurses in Lesotho, are authorized to write prescriptions for ART. We include only patients aged 10 years and older and weighing 35 kg or above (see the eligibility criteria). Thus, TDF/lamivudine/efavirenz is the standard treatment, which everybody will receive unless we discover they have renal impairment

Before dispensing ART, the study nurse will re-test the patient again for HIV as per national ART guidelines

Follow-up visit

The study nurse provides a follow-up date in 12–16 days, either at the health facility (VIBRA control) or with the VHW (VIBRA intervention, if the participant agrees), as their next ART visit

The study nurse documents the entire process in the patient booklet (“bukana”), including drugs prescribed and follow-up date, and fills in all government documents (patient file and registers) at the health facility responsible for the catchment area