Uptake of same-day initiation of HIV treatment among adult men and women in Malawi, South Africa, and Zambia: the SPRINT retrospective cohort study

Introduction

In 2017, the World Health Organization (WHO) began recommending “same-day initiation” (SDI) of treatment for patients with HIV considered clinically and personally ready for antiretroviral therapy (ART)¹. This recommendation was based on a series of randomized trials and observational studies that had demonstrated improved retention in care and viral suppression rates for patients offered SDI, compared to those offered what was then the standard of care, which typically required multiple clinic visits before a patient received an initial supply of antiretroviral medications (ARVs)². In the clinical trials, most of the improvement arose from a reduction in loss to follow up between testing positive for HIV and initiating ART. Observational studies have reported that among patients actually starting ART on the same day under routine care, loss to follow up during the first year after initiation has tended to be higher than in the pre-same day initiation period^3,4, but these studies have generally compared outcomes among patients who started on the same day to outcomes among those known to have started within a specified number of days, ignoring patients who never started ART at all.

In response to the WHO recommendation, many countries adopted SDI into their national guidelines. Instructions to healthcare facilities as to exactly how to implement SDI and to which patients it should be offered, however, were not precise, allowing the interval between a patient’s first clinic visit and ART initiation to be determined by provider judgment and/or patient preference. Time intervals from a patient’s initial presentation (HIV diagnosis or first HIV-related healthcare interaction) to initiation of ART are not routinely reported in electronic medical record (EMR) systems, which typically only create a record for a patient starting at the time of ART initiation. Little evidence is available on the proportion of patients actually starting ART on the same day or the characteristics of those who do or do not, including age, sex, and other characteristics. Without this information, it is difficult to understand observed differences or identify opportunities for improving care.

This paper reports quantitative results of the SPRINT study (Survey of Procedures and Resources for Initiating Treatment of HIV in Africa). It documents uptake of SDI, time to ART initiation for those not accepting SDI, and predictors of SDI for adult men and women in three high HIV burden countries in sub-Saharan Africa.

Methods

Results

We enrolled a total 3,374 participants whose ART initiation dates were between 01 January to 31 December 2018 in South Africa or between 01 July 2018 and 30 June 2019 in Malawi and Zambia. After excluding 30 participants who were found to be ineligible (under 18 years old or initiated treatment outside the study period), the final analytic sample included 3,344 participants (826 patients in Malawi, 534 in South Africa, and 1,984 in Zambia). CD4 counts and TB status were not available for patients in Malawi. There were no important differences in patient characteristics among the three countries, as shown in Table 2.

Discussion

In this study, we found that by 2020, uptake of SDI was extensive in Zambia and Malawi, reaching 80–90% of patients initiating or re-initiating ART. It was much less common in South Africa, where just 57% of patients initiated on the same day. We did not find significant differences in time to initiation by sex; men were equally likely to start on the same day as women. Among patients who did not initiate same-day, roughly one third in Malawi, half in South Africa, and nearly all in Zambia went on to initiate within 6 months; the rest had no record of treatment initiation by the end of the 6-month follow-up period.

We found several other publications that reported the rate of SDI in various countries in sub-Saharan Africa, mostly at earlier time periods than our study, which was conducted between 2018 and 2020. A multi-country cohort study using data from The International epidemiology Databases to Evaluate AIDS (IeDEA) Network through 2018, including South Africa but not Malawi or Zambia, reported an overall rate of SDI of 64%⁹. Three studies from South Africa were all completed roughly one year earlier than our study, in 2017-2018. The first, in Johannesburg, reported 20% uptake of SDI³. The second, in Johannesburg and Limpopo Province, reported that 40% of patients received SDI, with an increase in uptake from 30.3% at the start of the study period to 54.2% at the end⁶. The third, with data from four provinces, reported 54% SDI uptake in 2018, an increase from 18% in 2016¹⁰. The difference between these findings and our result of 57% SDI in South Africa in 2018-2020 likely reflects the impact of an additional year of facility experience in implementing the SDI guideline.

In Zambia, uptake of SDI increased from 42% to 75% of newly initiating patients between the beginning of 2016 and the beginning of 2018, a phenomenon attributed largely to the adoption of universal treatment eligibility in 2017¹¹. By the time our data were collected in 2018-2020, Zambia’s SDI rate had increased to more than 91% (Table 3). We did not find any published data on SDI uptake in Malawi to compare to our estimate of 88%. Reports from neighboring countries showed SDI rates of 65% in Zimbabwe⁷ and 52% in Mozambique in 2017¹²; in Botswana uptake increased from 28% to 59% between 2018 and 2019¹³. SPRINT adds both geographic breadth and, importantly, more recent experience to these prior publications.

Reasons for uptake of SDI or of having delays in ART initiation in our study are not clear. In our data from South Africa and Zambia, only the presence of TB symptoms or a WHO stage of III or IV predicted a delay in initiation. This result likely reflects concerns about starting ART while patients may be experiencing co-infections, such as TB or cryptococcal meningitis. Global guidelines continue to regard these conditions as justification for delaying ART initiation¹⁴, but recent studies suggest that many patients with TB symptoms can and should start ART immediately, as the risk of becoming lost to follow up if ART initiation is delayed may exceed the very low risk of experiencing TB immune reconstitution inflammatory syndrome¹⁵. Other reasons for delaying initiation may include clinicians’ individual views on SDI, patient preferences (e.g., concerns about stigma, disclosure, or side effects; feeling healthy or not in need of treatment¹⁶), and/or lack of resolve or resources to adopt new SDI procedures at some facilities.

At the same time, valuable as SDI may be as a strategy for minimizing loss to follow up before starting ART treatment, it is likely that some patients should indeed delay initiation, as they require more urgent medical care before starting ART or have personal concerns about or barriers to treatment that cannot be addressed in a single visit^17,18. The proportion of patients falling into this latter category is unclear, and it likely varies across different populations. Based on findings of the SLATE II trial in South Africa, a reasonable guess may be that 10–15% of patients are not good candidates for SDI¹⁹. If this is correct, then both Zambia and Malawi have achieved near-universal uptake of SDI. South Africa still has some distance to go, however, before it has saturated demand for SDI.

The advent of COVID-19 as a major health risk in all three study countries as of the second quarter of 2020 is likely to have changed both patient and provider behavior with regard to ART initiation. On one hand, COVID-19 morbidity, fear of transmission, and societal restrictions kept many potential patients away from the clinic. In South Africa, for example HIV initiations are known to have fallen by 28% in the first year of the pandemic¹⁹. Conversely, the desire to minimize personal interaction and clinic visits to avoid COVID-19 transmission could have favored SDI for patients who did make it to the clinic to start ART. It is also not clear whether provider and/or patient behavior will revert to earlier norms as pandemic restrictions wane or will sustain any changes that were made. A new round of data collection will be needed to answer those questions.

The SPRINT study had a number of limitations. Our final enrolled sample size was smaller than intended, due to resource limitations that shortened the data collection period. We relied entirely on routinely collected data, which resulted in many missing values for key variables. Despite every effort to enroll a representative sample of patients eligible for ART initiation, we are not confident that all patients who did not initiate ART during the study period were captured in Zambia, potentially leading to overestimates of total initiation in Zambia. Finally, we cannot discern from our data exactly why certain patients faced a delay in starting ART—whether it was a result of patient or provider preference, patient condition, social pressures, or some other barrier. To achieve the full potential of SDI in increasing treatment uptake for those who are eligible and willing—and not creating risks for or coercing those who are not—a better understanding of how decisions are made at healthcare facilities would be of value.