Persistence on oral pre-exposure prophylaxis (PrEP) among female sex workers in eThekwini, South Africa, 2016-2020.

BACKGROUND: Despite the established efficacy of PrEP to prevent HIV and the advantages of a user-controlled method, PrEP uptake and persistence by women in both trials and demonstration projects has been suboptimal. We utilized real-world data from an HIV service provider to describe persistence on oral PrEP among female sex workers (FSW) in eThekwini, South Africa.
METHODS: We examined time from PrEP initiation to discontinuation among all FSW initiating PrEP at TB HIV Care in eThekwini between 2016-2020. We used a discrete time-to-event data setup and stacked cumulative incidence function plots, displaying the competing risks of 1) not returning for PrEP, 2) client discontinuation, and 3) provider discontinuation. We calculated hazard ratios using complementary log-log regression and sub-hazard ratios using competing risks regression.
RESULTS: The number of initiations increased each year from 155 (9.3%, n = 155/1659) in 2016 to 1224 (27.5%, n = 1224/4446) in 2020. Persistence 1-month after initiation was 53% (95% CI: 51%-55%). Younger women were more likely to discontinue PrEP by not returning compared with those 25 years and older. Risk of discontinuation through non-return declined for those initiating in later years. Despite the COVID-19 pandemic, a greater number of initiations and sustained persistence were observed in 2020.
CONCLUSIONS: Low levels of PrEP persistence were observed, consistent with data among underserved women elsewhere. Encouragingly, the proportion of women persisting increased over time, even as the number of women newly initiating PrEP and staff workload increased. Further research is needed to understand which implementation strategies the program may have enacted to facilitate these improvements and what further changes may be necessary.

Introduction

Nearly one million people are newly infected with HIV annually in South Africa, constituting about 15% of global incident infections [1]. Female sex workers (FSW) bear a disproportionate burden of disease in the country. Estimates suggest that 60% of cisgender FSW are living with HIV compared with 19% of other adults of reproductive age [1-4]. FSW experience high levels of violence from clients, non-paying partners, sex work managers, and others [5,6]. This coupled with arrest, economic necessity to accept unsafe work conditions, and other power imbalances often compromise their ability to negotiate consistent condom use [7-9]. Pre-exposure prophylaxis for HIV prevention (PrEP) is an efficacious and user-controlled option to prevent new HIV infections [10,11]. Daily oral PrEP can be used autonomously and discreetly, without the need of partner or client involvement, and presents an opportunity for women to protect themselves from HIV [12,13].

Despite the HIV protection conferred by PrEP, with some estimates suggesting that daily use reduces acquisition by 79–85% among women [10,11], PrEP persistence among FSW in trial settings and demonstration projects has been low [14,15]. Even if freely available, many factors influence a woman’s decision to initiate and continue taking PrEP, including knowledge, side-effects, and accessibility of PrEP, along with actual and perceived risk of HIV acquisition, and PrEP stigma and social influence [16-19].

South Africa became the first country in Sub-Saharan Africa to implement PrEP as part of their national strategy for HIV prevention and began providing PrEP to FSW in 2016 [20]. PrEP has been primarily delivered through specific programs, which have existing HIV services in place and established rapport with community groups. The objective of this analysis was to describe PrEP persistence among cisgender FSW accessing PrEP in real-world conditions in eThekwini, KwaZulu-Natal from 2016 to 2020.

Methods

To describe PrEP persistence among FSW, we utilized data collected by TB HIV Care as part of routine service delivery. TB HIV Care is a South African non-profit organization that serves as the country’s largest PrEP provider for young women and FSW and began providing PrEP to FSW in 2016. They now operate at multiple sites across five provinces and offer services through mobile van health clinics and drop-in center wellness clinics.

The study population for this analysis includes cisgender FSW assigned female sex at birth who initiated PrEP through TB HIV Care in eThekwini between September 1st, 2016, and December 31st, 2020. Women would have been eligible to begin PrEP through TB HIV Care if they were already accessing prevention services (e.g. testing for pregnancy, STIs, or HIV; family planning) through the program serving FSW and were HIV-negative.

Data for this study come from a site-level register that is maintained to track PrEP uptake and persistence over time and manage patient follow-up and scheduling. This register has individual-level data on the date of first PrEP initiation and the outcomes of subsequent monthly visits, including whether or not individuals stopped and restarted PrEP. We followed women from PrEP initiation to discontinuation or administrative censoring at 12 months or December 2020, whichever came first. Discontinuation was defined as a composite outcome based on 1) not attending two consecutive visits (not returning for PrEP), 2) attending a monthly appointment and the client choosing to discontinue PrEP (client discontinuation), or 3) attending a monthly appointment and the clinician deciding to discontinue PrEP (provider discontinuation). Two consecutive missed visits was used to define discontinuation in alignment with TB HIV Care’s PEPFAR reporting definition for loss to follow-up. If a client misses one visit, but returns the next month, the program notes this client as not attending a visit but continuing on PrEP. If a client misses two consecutive visits and returns subsequently, the program defines her as a “restart.”

We examined time-to-PrEP discontinuation using a discrete time-to-event data setup, with person-periods defined for each month in which a woman was observed. We refer to the complement of PrEP discontinuation (i.e. ‘survival’ from discontinuation) as PrEP persistence. We plotted stacked cumulative incidence functions to show the differential risk of types of PrEP discontinuation (client discontinuation, provider discontinuation, not returning for PrEP) over time. We stratified analyses by age and era-of-initiation, defined as the year in which a woman initiated PrEP (2016–2020). We calculated overall, “cause-specific” hazard ratios (CHR) for discontinuation by age and year of initiation using a complementary log-log regression model. We calculated subdistribution-hazard ratios (SHR) for each specific type of PrEP discontinuation using Fine and Gray survival models [21]. Results were determined to be statistically significant if the 95% confidence interval around the hazard ratio did not overlap with the line of no difference, which is 1 in the case of ratio measures. All analyses were conducted using Stata 14.2 (StataCorp, College Park, Texas, USA).

Results

There were a total of 2776 FSW newly initiating PrEP at TB HIV Care in eThekwini between 2016 and 2020 and included in these analyses. Approximately 60% were women ages 25 years and older (1662/2762). The absolute number of PrEP initiations increased over time, and the percentage of PrEP initiations among those who were seen by the program and HIV-negative increased substantially in 2019 and 2020: 155/1659 (9.3%) in 2016, 211/3235 (6.5%) in 2017, 428/6042 (7.1%) in 2018, 756/5789 (13.1%) in 2019, and 1224/4446 (27.5%) in 2020 (Fig 1). Based on the Kaplan-Meier survival function, PrEP persistence was 53% (95% CI: 51%-55%) 1-month after initiation, 33% (95% CI: 31%-35%) 4-months after initiation, and 18% (95% CI: 16%-19%) 7-months after initiation. By 12-months, 9% (95% CI: 7%-10%) persisted on PrEP. Details of the Kaplan-Meier survivor function are provided in the S1 Appendix. Among those who discontinued (n = 2210), 13% restarted during the observation period (287/2210), with a median time from discontinuation to restart of 3 months (IQR: 3–5).

Fig 1

Number of PrEP eligible (HIV-negative and accessing services through TB HIV Care) and number and percentage of PrEP initiations each year among female sex workers in Durban, South Africa, 2016–2020.

At 1-month after initiation, 56% (95% CI: 54%-59%) of women ≥25 years old persisted on PrEP compared with 48% (95% CI: 45%-51%) of women <25 years old. The higher PrEP persistence seen in women ≥25 years was predominantly due to better attendance at follow-up visits compared with women <25 years (SHR for program-defined loss to follow-up: 0.82, 95% CI: [0.76, 0.88]). There were no significant differences by age in client-initiated or provider-initiated discontinuation (Table 1).

Table 1

Hazard of PrEP discontinuation and sub-hazard ratios of two consecutive missed visits, client-initiated discontinuation, and provider-initiated discontinuation among 2776 female sex workers initiating PrEP through TB HIV Care in Durban, South Africa 2016–2020.

	UNIVARIABLE
	Number of initiations	Discontinuation (composite outcome)	Two consecutive missed visits (n = 1986)	Client-initiated discontinuation (n = 217)	Provider-initiated discontinuation (n = 7)
		Hazard ratio (95% CI)	Sub-hazard ratio (95% CI)
Age 1
<25 years old	1102	ref	ref	ref	ref
25+ years old	1662	0.80 (0.74, 0.86)	0.84 (0.79, 0.91)	0.97 (0.74, 1.26)	0.91 (0.20, 4.10)
Year 2
2016	155	ref	ref	ref	ref
2017	211	0.99 (0.82, 1.19)	0.96 (0.80, 1.16)	0.89 (0.37, 2.14)	0.73 (0.05, 11.72)
2018	428	0.84 (0.71, 1.00)	0.86 (0.73, 1.01)	1.02 (0.48, 2.16)	1.41 (0.16, 12.56)
2019	756	0.88 (0.75, 1.03)	0.67 (0.57, 0.78)	3.41 (1.75, 6.63)	0.20 (0.01, 3.09)
2020	1224	0.82 (0.70, 0.96)	0.83 (0.71, 0.96)	0.35 (0.16, 0.77)	Too few events
	INCLUDING BOTH AGE AND YEAR IN THE SAME MODEL
		Hazard ratio (95% CI)	Sub-hazard ratio (95% CI)
Age 1
<25 years old	1102	ref	ref	ref	ref
25+ years old	1662	0.80 (0.74, 0.86)	0.82 (0.76, 0.88)	1.10 (0.85, 1.43)	0.85 (0.18, 3.98)
Year 2
2016	155	Ref	ref	ref	ref
2017	211	0.96 (0.80, 1.16)	0.94 (0.78, 1.12)	0.90 (0.38, 2.16)	0.72 (0.04, 11.67)
2018	428	0.83 (0.70,0.98)	0.84 (0.72, 0.99)	1.02 (0.48, 2.17)	1.40 (0.15, 13.10)
2019	756	0.85 (0.72,0.99)	0.64 (0.55, 0.75)	3.46 (1.78, 6.71)	0.19 (0.01, 3.47)
2020	1224	0.82 (0.70, 0.96)	0.82 (0.71, 0.95)	0.36 (0.16, 0.78)	Too few events

1Age data missing for n = 12 (0.4%);

2Year of initiation data missing for n = 2 (0.07%).

PrEP persistence improved over the course of the program (Fig 2). In 2019, 62% of women persisted on PrEP 1-month after initiation (95% CI: 58%-65%). By comparison, in 2016, 52% of women persisted on PrEP 1-month after initiation (95% CI: 43%-59%). Women initiating PrEP in 2018 (SHR: 0.84, 95% CI: [0.72, 0.99]), 2019 (SHR: 0.64, 95% CI: [0.55, 0.75]) and 2020 (SHR: 0.82, 95% CI: [0.71, 0.95]) were statistically significantly less likely to stop coming back for their PrEP compared to those initiating in 2016, when accounting for the competing risks of client-initiated and provider-initiated discontinuation. Interestingly, there was a statistically significantly greater risk of client-initiated discontinuation in 2019 compared with 2016, with 150 client-initiated discontinuations out of the 756 who initiated in 2019, or 19.8%, (SHR: 3.41, 95% CI: [1.75, 6.63]) (Table 1).

Fig 2

Stacked cumulative incidence functions plotting the competing risks of those who remained on PrEP, those who did not return (two consecutive missed visits), client-initiated discontinuation, and provider-initiated discontinuation among 2776 female sex workers initiating PrEP through TB HIV Care in eThekwini, South Africa 2016–2020.

Discussion

Among FSW accessing HIV prevention services from a real-world service provider in eThekwini, South Africa, the number of PrEP initiations increased each year from 2016 to 2020. PrEP persistence declined to 53% one month after initiation and to just 9% after one year. Younger women were more likely to discontinue PrEP due to missed visits compared with those 25 years and older. Risk of discontinuation due to missed visits declined for those initiating in 2018, 2019, and 2020, suggesting improvements over the life of the program in helping women to stay engaged. Despite the disruptions to the healthcare infrastructure created by the COVID-19 pandemic, the program reported more initiations, sustained improvements in persistence, and a lower risk of client-initiated stops among those initiating in 2020.

Poor PrEP persistence may challenge its real-world utility. The low levels of persistence seen in this study and the sharp decline at one-month are consistent with what has been reported in trials, including the FEM-PrEP study [22] and VOICE [23]. The TAPS demonstration study with FSW in South Africa also indicated that PrEP use declines to 50% one month after initiation and continues to decline after that [14]. The real-world data presented here reinforce the need for effective implementation strategies to improve PrEP persistence.

Losses were highest among those under 25 years, which is also the group of FSW at the highest risk of HIV acquisition. Nearly 30% of all new infections in South Africa are among young women and by age 25, 70% of FSW have been infected with HIV [24]. Younger women tend to have lower levels of HIV-related knowledge and lower risk perception [25]. Additionally, younger FSW may face specific challenges associated with their youth: less experience in the industry, less social support and fewer network ties, greater vulnerability to violence, lack of financial autonomy, and underdeveloped self-efficacy [26,27]. Strategies to promote PrEP persistence may need to be tailored to the specific challenges and needs of youth.

Over the life of the program, a number of changes have been implemented, both in terms of the goals of the program and the strategies implemented to try to achieve these goals. At the outset of the program, the primary goal was to try to promote PrEP uptake. As the program evolved, PrEP persistence grew to be a more central concern, with CDC/PEPFAR adding current users of PrEP as an official program target in 2019. The shifting priorities of the program may help explain the greater focus given to persistence and the observed improvements over time. Additionally, the program instituted several implementation strategies that aimed to address different barriers to PrEP persistence. The program added staff in June 2019 that included case managers and social workers. These additional staff meant more dedicated resources and greater flexibility to manage new PrEP users. The expanded use of the case management approach allowed for staff to call those who may have missed appointments. This closer follow-up may also help explain the reason for the increased risk of client-initiated discontinuation in 2019, as staff were actually able to ascertain and record that a woman no longer wanted to be on PrEP.

The data presented here show that the program was largely resilient to the interruptions caused by COVID-19, with a consistent increase in the number of initiations and improved persistence among those who began PrEP in 2020. Though empiric data on the impact of COVID-19 on HIV services in Sub-Saharan Africa are limited, most suggest that patient care was interrupted by pandemic restrictions due to lower supply of drugs and fewer patient visits [28-30]. In a national survey in South Africa that recruited approximately 19,000 individuals via social media, it was found that 13.2% were unable to pick up their medications during the pandemic [29]. The implementation strategies started by the program coupled with the fact that HIV prevention and treatment services remained “essential” in South Africa during the COVID-19 pandemic may have made the program more resilient to the shocks of the pandemic.

There are three key limitations of this study. First, the primary outcome in this study is PrEP persistence rather than adherence, which may be better captured through pill counts, electronic monitoring, or pharmacological samples, and arguably is an important measure of whether a woman was protected from acquiring HIV. PrEP persistence is probably a highly specific but not perfectly sensitive measure of PrEP adherence. PrEP was not available from other sources in the study setting during the study period (not persisting on PrEP is a good marker of not adhering to PrEP). Contrariwise, it is unlikely that women would return to pick up PrEP if they did not intend to take it (PrEP persistence is not a guarantee of PrEP adherence, but it is probably a reasonable proxy). If anything, we have overestimated PrEP adherence and our central conclusion (PrEP adherence is too low) is unchanged. A second limitation is that the frequency of PrEP refill visits changed during the study period. At the start of the program, women were seen monthly to be given their PrEP. When the guidelines were updated to allow for multi-month dispensing, women were seen at 1-month and thereafter 3-monthly (e.g. 1-month, 4-months, 7-months, etc.) to be given their PrEP. In many instances, however, the program did see the client in the intervening months between PrEP refill visits and would document whether an individual was still taking PrEP. While in later years this might have limited our ability to detect PrEP discontinuation with the same speed (e.g., discontinuation that occurred at month 2 might not be detected until month 4,) we chose to retain the definition of two missed monthly visits for discontinuation both to ensure comparability across the years and because the program’s register still documents monthly contact with PrEP users. All discontinuations would still be detected within the outcome window (1 year) overall estimates of PrEP persistence at 4- and 7-months should not be affected. As a final limitation, because of limited data availability, demographic and/or behavioral risk data beyond age and year of PrEP initiation were not available to thoroughly assess predictors of persistence. Understanding who is at risk of discontinuation and reasons for discontinuation will be an important contribution to better tailoring strategies to promote PrEP persistence.

The need for PrEP, unlike treatment for HIV, depends heavily on individual risk-assessment and readiness. Some of the improved persistence over time could be explained by program staff better refining who they started on PrEP, that is, better identifying women who were in need of and who understood the benefit of taking PrEP or may in part be due to the role of diffusion of information (increasing PrEP awareness and awareness of the program) and greater acceptability among peers, partners, and others in the community. While this study describes how the program was able to make gradual improvements in PrEP persistence over time while reaching a larger number and proportion of FSW over time, further research on which implementation strategies may have spurred some of these incremental changes and the mechanism of action are critical to see the additional gains in persistence that are needed.

PrEP eThekwini survival analysis appendix.

(DOCX)

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12 Oct 2021

Submitted filename: Plos1reviewSep2021final.docx

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9 Dec 2021

We thank the reviewers for taking the time to review our manuscript and for your thoughtful and constructive comments. We have responded to your feedback, point-by-point, below.

Reviewer #1: INTRO:

1) PrEP persistence instead of persistence on PrEP sounds better and less clumsy

Thank you for this suggestion. We have replaced instances of “persistence on PrEP” with “PrEP persistence.”

2) Police arrest seems redundant

We have revised this simply to state “arrest,” to avoid the redundancy.

3) Reference 20 seems to be the wrong reference for line 115. Also the roll out happened with sex workers first - https://www.prepwatch.org/early-lessons-south-africa-rollout/

Thank you very much for this point of clarification. This was an incorrect statement. We have revised it and referenced PrEP Watch instead.

METHODS:

4) When you looked at PrEP initiation were these all new initiations or did some people stop and then initiate again? Please clarify in the methods how your cohort is defined. Results indicate that some were restarts.

This is an important question; thank you for bringing this to our attention. Our study population is made up of unique individuals who initiated PrEP for the first time. Restarts were documented as events occurring during follow-up of these unique individuals in the program’s PrEP register. We have added language to clarify this in the Methods section.

5) There are different ways to define PrEP persistence – you could reference how other people have defined this and why you chose your definition. Please also explain why people had to miss 2 consecutive visits to be defined as “discontinued” It seems to be a more generous definition of persistence and may explain why your persistence is higher than other studies

Thank you for this point of clarification. Two consecutive missed months rather than one missed visit was used to define discontinuation, as this is the definition used by the program to define loss to follow-up. If a client misses one visit, but returns the next month, the program notes this client as not attending a visit but continuing on PrEP. If a client misses two consecutive visits and returns subsequently, the program defines her as a “restart.” We have added clarification of this to the Methods section (lines 159-164). Of additional note, this definition is in alignment with the PEPFAR definition used by the Monitoring and Evaluation team and across the PEPFAR funded program in South Africa.

6) Did you bring your participants back for monthly visits in your program? This is not comparable to most standard of care that would see PrEP clients after a month and then 3 monthly. Please describe the program in the methods and justify why this is “real world implementation” (line 118). Please also discuss how many FSW accessed the program in total year on year and how many of the non infected FSW refused to take PrEP. It is important to have context to be able to understand what the results mean.

Thank you for this question. We agree that further information is needed here to clarify how frequently clients were seen by the program. When the program first began delivering PrEP, clients would be seen on a monthly basis to be given their PrEP. When the guidelines were updated to allow for multi-month dispensing and for women to been seen at 1 month and then again 3-monthly (e.g. 4, 7, 10 months, etc.), the program also updated their procedures accordingly. In many instances, however, the program did see the client in the intervening months between PrEP refill visits and could document whether she was still taking PrEP.

This could partially explain why for the later years of the program, you see steeper numbers discontinuing at the formal intervals (e.g. 4 months and 7 months) compared with intervening months (e.g. 2 and 3 months), but it is still possible that women may discontinue at intervening months in the later years.

While this change in frequency of visits is a limitation, we chose to retain the definition of two missed monthly visits for discontinuation both to ensure comparability across the years and because the program’s register still documents monthly contact with PrEP users.

We have now added detailed reference to this in the Limitations section of the Discussion (lines 317-326).

With regard to the second portion of your question on how many FSW accessed the program, please see the below response to comment # 9; we have added the number of FSW eligible for PrEP (accessing services and HIV-negative) each year as a denominator for the number taking up PrEP.

7) Some results are reported as “significant” please define in the methods what you mean by this

Results were determined to be statistically significant if the 95% confidence interval around the hazard ratios did not overlap with the line of no difference (which is 1 in the case of ratio measures). We have added a line describing this in the Methods.

RESULTS:

8) General comment on the results is that there are no denominators so it is very difficult to interpret your % results.

Thank you for this. We have provided a table in the Appendix that details the number at risk at the start of each time period, the number who experienced the outcome of discontinuation, the net lost, and the corresponding survivor function. The percentage retained at each monthly interval are based on a Kaplan-Meier survivor function (conditional probability), which accounts for more complex survival data (e.g. adequately accounting for those individuals who were administratively censored: those who initiated in the last few months of the program and did not have enough follow-up months to determine their outcome). We feel that providing denominators would not adequately convey this, and so instead have provided the table to give further detail of the risk sets for each month.

9) PrEP initiations increased year on year – please include denominators to understand if the project was scaling up or if you were seeing the same numbers of people and more were taking up PrEP. So something like of the xxx FSW eligible to receive PrEP yyy initiated PrEP per year.

We agree with your feedback and have now added into the results the number who were eligible each year for PrEP and the percentage taking up PrEP (lines 194-198). We have also added a new figure (new Figure 1) to visually depict the increase in percentage of FSW initiating PrEP over time.

10) Please give the n/N for the PrEP persistence figures – need to see the denominators to be able to interpret your results.

Please see our above response to comment # 8.

11) PrEP persistence was 53% (95% CI: 51%-55%) 1 month after initiation, 33% (95% CI: 31%-35%) 4-months after initiation, and 18% (95% CI: 7-months after initiation. Is this overall? (line 162)

Thank you for this clarifying question. Yes – these results were for overall across all those initiating PrEP.

12) Please clarify how you know your results are significant? What statistical test did you use?

Thank you for this. As we noted above in response to comment # 7, groups were considered to be significantly different from one another if the 95% confidence intervals surrounding the hazard ratio did not overlap with 1. Where we do note “significance” in the results, we have now revised this to state “statistically significant” for added clarity.

DISCUSSION:

13) No limitations mentioned

We have now added a limitations paragraph to the Discussion section with the three main limitations of this study (lines 312-330).

FIGURES AND LEGENDS

14) Figure 1 legend is incomplete

Thank you for your careful review here. We have now corrected this, so the legend for Figure 1 is complete.

Reviewer #2: This is a well written and well done study on PrEP persistence in South Africa. While some of the descriptions of persistence and conclusions about age are not new, the study makes a valuable contribution to the literature with interesting findings related to persistence over time and during the pandemic. I enjoyed reading this paper and think it is important.

We thank you for your careful review and consideration. Please find responses to your points below.

• Can you describe more about the study population? It is stated that they were already accessing other care at TB HIV care or took part in a PrEP initiation campaign. Would you expect this population of FSW to be representative of FSW more broadly?

This is a really important point. Our study population is made up of those accessing services through or engaged with TB HIV Care in some way (from regularly testing for HIV, to picking up contraceptives, to operating out of a venue where TB HIV Care staff are familiar). This population may not be representative of all FSW (those missed may include those working in isolated environments, who are not otherwise interacting with the larger sex work community) but is certainly representative of those who may be reached with outreach services.

• Given the use of register data, please describe more about how you dealt with missing data and measurement error.

Thank you for this question. Data were complete for our primary independent variables (age and year of initiation). One component of our composite outcome was defined as not attending two consecutive visits, and individuals who missed two consecutive visits were classified as not returning for PrEP. Because of the structure of our outcome, we also did not have missing outcome data.

• Were reasons for discontinuation captured? This might be interesting to describe by years. For example, was it related to moving, change in behavior or something else.

We agree with your feedback that it would have been informative to present reasons for discontinuation, but unfortunately, the PrEP register we have access to does not capture this information. This is something we are hoping to explore further in future work (there is some ongoing qualitative work in the same population to look at exactly this).

Additionally, we have now noted in the Limitations section: “As a final limitation, because of limited data availability, demographic and/or behavioral risk data beyond age and year of PrEP initiation were not available to thoroughly assess predictors of persistence. Understanding who is at risk of discontinuation and reasons for discontinuation will be an important contribution to better tailoring strategies to promote PrEP persistence.”

• Given the way the categories are defined it seems as though there would be differential loss to follow up by group for other reasons unrelated to PrEP discontinuation ( e.g going to a new provider for PrEP) Can you describe how this may have impacted results?

During the study period, TB HIV Care was the sole provider of PrEP to this population, and so it is unlikely that women would have been able to continue their PrEP elsewhere. In this analysis, we have captured three different reasons for PrEP discontinuation: not returning for visits, client-initiated discontinuation, and provider-initiated discontinuation.

• The authors mention the role of partners and social influence but mostly focus on changes in clinic implementation to explain increases in persistence over time. What about the role of diffusion of information and social norms?

Thank you for this point. We have now made note in the Discussion section that changes in persistence over time may in part be due to the role of diffusion of information (PrEP awareness and awareness of the program) and greater acceptability among peers, partners, and others in the community.

Submitted filename: Plos1reviewSep2021final_18Nov2021.docx

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2 Mar 2022

Persistence on oral pre-exposure prophylaxis (PrEP) among female sex workers in eThekwini, South Africa, 2016-2020

PONE-D-21-28140R1

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Reviewer #1: No

Reviewer #2: No

7 Mar 2022

PONE-D-21-28140R1

Persistence on oral pre-exposure prophylaxis (PrEP) among female sex workers in eThekwini, South Africa, 2016-2020

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