Evaluation of HIV treatment outcomes with reduced frequency of clinical encounters and antiretroviral treatment refills: A systematic review and meta-analysis

Abstract

Background Global HIV treatment programs have sought to lengthen the interval between clinical encounters for people living with HIV (PLWH) who are established on antiretroviral treatment (ART) to reduce the burden of seeking care and to decongest health facilities. The overall effect of reduced visit frequency on HIV treatment outcomes is however unknown. We conducted a systematic review and meta-analysis to evaluate the effect of implementation strategies that reduce the frequency of clinical appointments and ART refills for PLWH established on ART. Methods and findings We searched databases​ between 1 January 2010 and 9 November 2021 to identify randomized controlled trials (RCTs) and observational studies that compared reduced (6- to 12-monthly) clinical consultation or ART refill appointment frequency to 3- to 6-monthly appointments for patients established on ART. We assessed methodological quality and real-world relevance, and used Mantel–Haenszel methods to generate pooled risk ratios (RRs) with 95% confidence intervals for retention, viral suppression, and mortality. We evaluated heterogeneity quantitatively and qualitatively, and overall evidence certainty using GRADE. Searches yielded 3,955 records, resulting in 10 studies (6 RCTs, 3 observational studies, and 1 study contributing observational and RCT data) representing 15 intervention arms with 33,599 adults (≥16 years) in 8 sub-Saharan African countries. Reduced frequency clinical consultations occurred at health facilities, while reduced frequency ART refills were delivered through facility or community pharmacies and adherence groups. Studies were highly pragmatic, except for some study settings and resources used in RCTs. Among studies comparing reduced clinical consultation frequency (6- or 12-monthly) to 3-monthly consultations, there appeared to be no difference in retention (RR 1.01, 95% CI 0.97–1.04, p = 0.682, 8 studies, low certainty), and this finding was consistent across 6- and 12-monthly consultation intervals and delivery strategies. Viral suppression effect estimates were markedly influenced by under-ascertainment of viral load outcomes in intervention arms, resulting in inconclusive evidence (RR 0.74, 95% CI 0.59–0.94, p = 0.015, 4 RCTs, very low certainty). There was similarly insufficient evidence to draw conclusions on mortality (RR 1.12, 95% CI 0.75–1.66, p = 0.592, 6 studies, very low certainty). For ART refill frequency, there appeared to be little to no difference in retention (RR 1.01, 95% CI 0.98–1.06, p = 0.473, 4 RCTs, moderate certainty) or mortality (RR 1.45, 95% CI 0.63–3.35, p = 0.382, 4 RCTs, low certainty) between 6-monthly and 3-monthly visits. Similar to the analysis for clinical consultations, no conclusions could be drawn on viral suppression (RR 0.60, 95% CI 0.41–0.88, p = 0.009, 3 RCTs, very low certainty). This systematic review was limited by the small number of studies available to compare 12- versus 6-monthly clinical consultations, insufficient data to compare implementation strategies, and lack of evidence for children, key populations, and low- and middle-income countries outside of sub-Saharan Africa. Conclusions Based on this synthesis, extending clinical consultation intervals to 6 or 12 months and ART dispensing intervals to 6 months appears to result in similar retention to 3-month intervals, with less robust conclusions for viral suppression and mortality. Future research should ensure complete viral load outcome ascertainment, as well as explore mechanisms of effect, outcomes in other populations, and optimum delivery and monitoring strategies to ensure widespread applicability.

Clinical outcomes after extended 12-month antiretroviral therapy prescriptions in a community-based differentiated HIV service delivery programme in South Africa: a retrospective cohort study

“…Our findings are consistent with those from existing research, although data are lacking. A recent systematic review compared clinical outcomes among PLHIV with reduced (6-to 12-monthly) clinical consultations to those among PLHIV with 3-monthly clinical visits [9]. All studies included in the review analysed PLHIV who were established on ART, and most utilised clinical outcomes with a 12-month duration.…”

“…However, little is known about the impact of extended ART prescriptions on clinical outcomes among PLHIV who are established on treatment [9]. Therefore, in this study we use data from a large community-based DSD programme in South Africa to investigate whether clinical outcomes among PLHIV given 12-month ART prescriptions differed from those given 6-month prescriptions.…”

Reducing time to differentiated service delivery for newly-diagnosed people living with HIV in Kigali, Rwanda: a pilot, unblinded, randomized controlled trial

“…In recognition of an increasingly diverse set of needs for the millions of people living with HIV (PWH) on antiretroviral therapy (ART), in 2016 the WHO recommended implementation of differentiated service delivery (DSD) models [ 1 ]. Such approaches are feasible, acceptable, and achieve equivalent or improved retention in care and viral suppression compared to standard treatment [ 2 – 7 ]. Many countries have adopted facility-based DSD models allowing PWH established on ART to be seen less frequently for clinical assessments (e.g.…”

Factors associated with enrollment into differentiated service delivery model among adults with HIV in Kenya

“…With the scale-up of antiretroviral therapy (ART) with fewer side effects, many people living with HIV in countries with mature HIV programs are established on treatment and require fewer interactions with the healthcare system. DSD for HIV treatment services may encompass various strategies, including multimonth dispensing (MMD), increased time between clinic visits, fast-track ART refills, task-shifting from physicians to other types of health providers, and community ART distribution [4][5][6][7]. For clients, DSD reduces the financial burden of transportation and the time spent traveling to/from the health facility and waiting for appointments.…”

“…A systematic review found 39 studies on ART refill frequency published between 2018 and 2019 [11]; however, only one of the studies was conducted in Kenya, and this study did not evaluate the facility-based, fast-track model, which includes ≥3MMD. Similarly, a systematic review examining the effect of reduced frequency of clinical encounters and antiretroviral drug refills on retention and viral load included only one study from Kenya, which included a randomized trial [7]. Whereas most DSD research to date has focused on clinical outcomes, little is known about individual and facility-level factors associated with being on at least 3MMD among eligible clients and switching out from ≥3MMD to <3MMD, a better understanding of these factors is essential to improve implementation of DSD as a key model for HIV service delivery.…”