Cervical cancer screening delay and associated factors among women with HIV in Lesotho: a mixed-methods study.

BACKGROUND: Cervical cancer is the fourth most common cancer in women worldwide, and women with human immunodeficiency virus (HIV) are particularly at risk of developing it. Regular screening effectively prevents morbidity and mortality. This mixed-methods study quantitatively assessed cervical cancer screening uptake and qualitatively explored the process of undergoing cervical cancer screening to understand possible reasons for delayed screening among women with HIV in Lesotho. METHODS: Between October 2020 and March 2022, the Viral load Triggered ART care in Lesotho (VITAL) trial enrolled women aged 18 years and older with HIV who were taking antiretroviral therapy (ART). Cervical cancer screening delay was defined as reporting a screening that occurred more than two years ago or never having been screened. Cervical cancer screening uptake and the association between screening delay and sociodemographic variables were assessed using a multivariable mixed-effects logistic regression model accounting for clustering at clinic level. In-depth interviews were conducted with 16 women to obtain information on awareness, perceptions, and barriers to cervical cancer screening and were analyzed using thematic analysis. RESULTS: Quantitative data were available for 3790 women. Among them, cervical cancer screening was delayed in 1814 (47.9%), including 1533 (40.5%) who were never screened. Compared to women aged 25 to 39 years, women aged 18 to 24 years (adjusted odds ratio (aOR) 2.8; 95% confidence interval (CI) 2.1-3.7), women aged 40 to 59 years (aOR 1.3; CI 1.1-1.6), and women older than 60 years (aOR 3.9; CI 3.0-5.1) were at higher risk of screening delay. Furthermore, time on ART below 6 months (aOR 1.6; CI 1.1-2.3) compared to above 6 months was associated with screening delay. Qualitative data identified limited awareness of cervical cancer risks and screening guidelines, misconceptions and fears created by the influence of other women's narratives, and low internal motivation as the main barriers to screening uptake. CONCLUSIONS: Cervical cancer screening delay was common. Limited personal awareness and motivation as well as the negative influence of other women were the primary internal barriers to cervical cancer screening. Awareness and screening campaigns in Lesotho should consider these factors. TRIAL REGISTRATION: clinicaltrials.gov, NCT04527874, August 27, 2020.

SMSs as an alternative to provider-delivered care for unhealthy alcohol use: study protocol for Leseli, an open-label randomised controlled trial of mhGAP-Remote vs mhGAP-Standard in Lesotho.

BACKGROUND: The World Health Organization's (WHO) Mental Health Gap Action Programme (mhGAP) is a validated intervention that can be provided by non-specialised healthcare workers to individuals with unhealthy alcohol use. However, it typically requires several in-person sessions at a health facility, which may limit its feasibility and effectiveness in remote settings. This trial compares mhGAP-Standard, a 4 to 6 in-person session intervention, to mhGAP-Remote, a 1 in-person session intervention followed by 8 week of short message service (SMS) in Lesotho. We hypothesise that mhGAP-Remote is superior to mhGAP-Standard in reducing alcohol use (as detailed by the primary and secondary outcomes below). METHODS: This is a two-arm randomised open-label multicentre superiority trial. Participants allocated to mhGAP-Standard receive 4 in-person sessions using motivational interviewing, identifying triggers, and alternative behaviours, with the option of two additional booster sessions. Participants in the mhGAP-Remote arm receive 1 in-person session covering the same content, followed by standardised SMSs over 8 weeks that reinforce intervention content. Non-specialist providers deliver the intervention and receive weekly supervision. Adults (Nplanned = 248) attending participating health facilities for any reason and who meet criteria for unhealthy alcohol use based on the Alcohol Use Disorders Identification Test ([AUDIT] score ≥ 6 for women, ≥ 8 for men) are individually randomised to the two arms (1:1 allocation, stratified by participant sex and age (≥ 50 vs < 50 years old). Follow-up assessments occur at 8, 20, and 32 weeks post-randomisation. The primary outcome is change in self-reported alcohol use (continuous AUDIT score), from baseline to 8 weeks follow-up. Change in the AUDIT from baseline to 20 and 32 weeks follow-up is a secondary outcome. Change in the biomarker phosphatidylethanol (secondary), liver enzyme values in serum (exploratory), and HIV viral load (for people with HIV only; exploratory) are also evaluated from baseline throughout the entire follow-up period. A linear regression model will be conducted for the primary analysis, adjusted for the stratification factors. Three a priori sensitivity analyses for the primary outcome are planned based on per protocol treatment attendance, recovery from unhealthy alcohol use, and clinically significant and reliable change. DISCUSSION: This trial will provide insight into feasibility and effectiveness of a shortened and primarily SMS supported version of mhGAP, which is especially relevant for settings where regular clinic attendance is a major barrier. TRIAL REGISTRATION: clinicaltrials.gov NCT05925270 . Approved on June 29th, 2023.

HIV viral suppression in children and adolescents 2 years after transition to dolutegravir: a multicentre cohort study.

BACKGROUND: Treatment failure is common among children and adolescents with HIV. Antiretroviral therapy (ART) containing dolutegravir has recently been rolled out across Africa, though long-term real-world data in paediatric populations are lacking. Here, we report treatment outcomes among children and adolescents in Lesotho who transitioned from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based to dolutegravir-based ART through 2 years' follow-up. METHODS: Data were derived from two open cohort studies in Lesotho. Children and adolescents aged less than 18 years who transitioned from NNRTI-based to dolutegravir-based ART at least 18 months before data closure were included. We report viral load results less than 12 months before, 12 (window: 6-17) months after, and 24 (window: 18-29) months after transition to dolutegravir. Associations of pretransition demographic and clinical factors with 24-month viraemia were assessed through multivariable logistic regression. RESULTS: Among 2126 included individuals, 1100 (51.7%) were female individuals, median age at transition to dolutegravir was 14.0 years [interquartile range (IQR) 11.5-15.8], and median time taking ART at transition was 7.6 years (IQR 4.4-10.6). Among those with a viral load result at the respective time points, viral suppression to less than 50 copies/ml was achieved by 1635 of 1973 (82.9%) less than 12 months before, 1846 of 2012 (91.8%) 12 months after, and 1725 of 1904 (90.6%) 24 months after transition to dolutegravir. Pretransition viraemia was associated with viraemia at 24 months, though more than 80% of individuals with pretransition viraemia achieved resuppression to less than 50 copies/ml at 24 months. CONCLUSION: The proportion of children and adolescents with viral suppression increased after transition to dolutegravir, though further progress is needed to reach global targets.

Clinical Relevance of Human Immunodeficiency Virus Low-level Viremia in the Dolutegravir era: Data From the Viral Load Cohort North-East Lesotho (VICONEL).

Background: Human immunodeficiency virus low-level viremia (LLV) is associated with subsequent treatment failure at least with non nucleoside reverse transcriptase inhibitor (NNRTI)-containing antiretroviral therapy. Data on implications of LLV occurring under dolutegravir, which has largely replaced NNRTIs in Africa, are scarce, however. Methods: We included adults with human immunodeficiency virus in Lesotho who had ≥2 viral loads (VLs) taken after ≥6 months of NNRTI- or dolutegravir-based antiretroviral therapy. Within VL pairs, we assessed the association of viral suppression (<50 copies/mL) and low- and high-range LLV (50-199 and 200-999 copies/mL, respectively) with virological failure (≥1000 copies/mL) using a mixed-effects regression model. Participants could contribute VLs to the NNRTI and the dolutegravir group. Results: Among 18 550 participants, 12 216 (65.9%) were female and median age at first VL included was 41.2 years (interquartile range, 33.4-51.5). In both groups, compared with a suppressed VL, odds of subsequent virological failure were higher for low-range LLV (NNRTI: adjusted odds ratio; 95% confidence interval: 1.9; 1.4-2.4 and dolutegravir: 2.1; 1.3-3.6) and high-range LLV (adjusted odds ratio; 95% confidence interval, 4.2; 3.1-5.7 and 4.4; 2.4-7.9). Conclusions: In the dolutegravir era, LLV remains associated with virological failure, endorsing the need for close clinical and laboratory monitoring of those with a VL ≥50 copies/mL.

Two-Year Outcomes of Treatment-Experienced Adults After Programmatic Transitioning to Dolutegravir: Longitudinal Data From the VICONEL Human Immunodeficiency Virus Cohort in Lesotho.

In the Viral Load Cohort North-East Lesotho (VICONEL) human immunodeficiency virus cohort, 14 242 adults had transitioned from efavirenz- or nevirapine-based antiretroviral therapy (ART) to dolutegravir-based ART by October 2021. Rates of viral suppression to <50 copies/mL were 84.8%, 93.9%, and 95.4% before, 12 months after, and 24 months after transition, respectively. Sex, age, pretransition viral load, and treatment backbone correlated with 24-month viremia.

Assessment of a viral load result-triggered automated differentiated service delivery model for people taking ART in Lesotho (the VITAL study): Study protocol of a cluster-randomized trial.

INTRODUCTION: To sustainably provide good quality care to increasing numbers of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in resource-limited settings, care delivery must shift from a "one-size-fits-all" approach to differentiated service delivery models. Such models should reallocate resources from PLHIV who are doing well to groups of PLHIV who may need more attention, such as those with treatment failure. The VIral load Triggered ART care Lesotho (VITAL) trial assesses a viral load (VL)-, participant's preference-informed, electronic health (eHealth)-supported, automated differentiated service delivery model (VITAL model). With VITAL, we aim to assess if the VITAL model is at least non-inferior to the standard of care in the proportion of participants engaged in care with viral suppression at 24 months follow-up and if it is cost-saving. METHODS: The VITAL trial is a pragmatic, multicenter, cluster-randomized, non-blinded, non-inferiority trial with 1:1 allocation conducted at 18 nurse-led, rural health facilities in two districts of northern Lesotho, enrolling adult PLHIV taking ART. In intervention clinics, providers are trained to implement the VITAL model and are guided by a clinical decision support tool, the VITALapp. VITAL differentiates care according to VL results, clinical characteristics, sub-population and participants' and health care providers' preferences. EXPECTED OUTCOMES: Evidence on the effect of differentiated service delivery for PLHIV on treatment outcomes is still limited. This pragmatic cluster-randomized trial will assess if the VITAL model is at least non-inferior to the standard of care and if it is cost saving. TRIAL REGISTRATION: The study has been registered with clinicaltrials.gov (Registration number NCT04527874; August 27, 2020).

eHealth supported multi-months dispensing of antiretroviral therapy: a mixed-methods preference assessment in rural Lesotho.

BACKGROUND: Multi-month dispensing (MMD) of antiretroviral therapy (ART) represents one approach of differentiated service delivery (DSD) aiming to improve quality and cost-effectiveness for HIV services in resource-limited settings. However, reduction in clinic visits for people living with HIV (PLWH) should go along with out-of-clinic care tailored to PLWH`s preferences and comorbidities to maintain quality of care. eHealth supported MMD offers a potential solution. METHODS: Between October 2019 and January 2020 we assessed preferences on an eHealth supported MMD package among adult PLWH attending routine ART care at a rural clinic in Lesotho using a mixed-methods approach. Participants reported their preferences among different refill and eHealth options. They were invited to test automated text messages (SMS) informing about their viral load results, an automated tuberculosis symptoms screening call and telemedical support by an expert nurse. Telemedical service comprised a call-back option if participants required any additional support and adherence counselling for closer follow-up of participants with unsuppressed viral loads. After 6 weeks, participants were followed-up to assess perception of the chosen eHealth support using a qualitative approach. RESULTS: Among 112 participants (median age = 43 years; 74% female), 83/112 (75%) preferred MMD for 6-12 months (median = 9 months, IQR = [5, 12]). Neither sex, age, employment, costs and time for travel to clinic, nor the duration of taking ART correlated with the MMD preference. All 17 participants attending routine viral load measurement wished to receive the result via SMS. Fifteen (19.2%) participants requested a telemedical nurse call-back during the study period. All participants with recent unsuppressed viral load (N = 13) requested telemedical adherence counselling for closer follow-up. Among 78 participants followed-up, 76 (97%) would appreciate having the call-back option in future. Seventy-five participants (67%) received and evaluated the automated symptomatic tuberculosis screening call, overall 71 (95%) appreciated it. CONCLUSIONS: The great majority of PLWH in this study preferred 6-12 months MMD and appreciated the additional eHealth support, including viral load results via SMS, telemedical nurse consultations and automated tuberculosis symptom screening calls. eHealth supported MMD packages appear to be a promising approach for DSD models and should be assessed for clinical endpoints and cost-effectiveness in larger studies.

The Suboptimal Pediatric HIV Viral Load Cascade: Multidistrict Cohort Study Among Children Taking Antiretroviral Therapy in Lesotho, Southern Africa.

BACKGROUND: Children living with HIV and taking antiretroviral therapy (ART) are a priority group for routine viral load (VL) monitoring. As per Lesotho guidelines, a VL ≥1000 copies/mL ("unsuppressed") should trigger adherence counseling and a follow-up VL; 2 consecutive unsuppressed VLs ("virologic failure") qualify for switching to second-line ART, with some exceptions. Here, we describe the pediatric VL cascade in Lesotho. METHODS: In a prospective open cohort study comprising routine VL results from 22 clinics in Lesotho, we assessed outcomes along the VL cascade for children who had at least 1 VL test from January 2016 through June 2020. Data were censored on February 10, 2021. RESULTS: In total, 1215 children received 5443 VL tests. The median age was 10 years (interquartile range 7-13) and 627/1215 (52%) were female; 362/1215 (30%) had at least 1 unsuppressed VL. A follow-up VL was available for 325/362 (90%), although only for 159/362 (44%) within 6 months of the first unsuppressed VL. Of those with a follow-up VL, 172/329 (53%) had virologic failure and 123/329 (37%) qualified for switching to second-line ART. Of these, 55/123 (45%) were ever switched, although only 9/123 (7%) were switched within 12 weeks of the follow-up VL. Delays were more pronounced in rural facilities. Overall, 100/362 (28%) children with an unsuppressed VL received a timely follow-up VL and, if required, a timely regimen switch. CONCLUSIONS: Despite access to VL monitoring, clinical management was suboptimal. HIV programs should prioritize timely clinical action to maximize the benefits of VL monitoring.

The viral load monitoring cascade in a resource-limited setting: A prospective multicentre cohort study after introduction of routine viral load monitoring in rural Lesotho.

INTRODUCTION: For HIV-positive individuals on antiretroviral therapy (ART), the World Health Organization (WHO) recommends routine viral load (VL) monitoring. We report on the cascade of care in individuals with unsuppressed VL after introduction of routine VL monitoring in a district in Lesotho. MATERIALS AND METHODS: In Butha-Buthe district 12 clinics (11 rural, 1 hospital) send samples for VL testing to the district laboratory. We included data from patients aged ≥15 years from Dec 1, 2015 to November 1, 2018. As per WHO guidelines VL <1000 copies/mL are considered suppressed, those ≥1000copies/mL unsuppressed. Patients with unsuppressed VL receive adherence counseling and follow-up VL within 8-12 weeks. Two consecutively unsuppressed VLs should trigger switch to second-line ART. For analysis of the VL monitoring cascade we defined care to be "according to guidelines" if patients with unsuppressed VL received a follow-up VL within <180 days and follow-up VL was either re-suppressed, or again unsuppressed and the individual was switched to second-line within 90 days. RESULTS: For 9,949 individuals 24,948 VL tests were available. The majority were female (73%), median age 41 years (interquartile range 33-52), and 58% seen at rural clinics. Overall, 25% (260/1028) of individuals were managed according to guidelines: 40% (410/1028) had a follow-up VL within 180 days of their initial unsuppressed VL and 25% (260/1028) of those either re-suppressed or switched to second-line within 90 days. Female patients were more likely to have a follow-up VL done, (p = 0.015). In rural clinics rates of two consecutively unsuppressed VLs were higher than in the hospital (64% vs. 44%, p<0.001), and rural clinics were less likely to switch these patients to second-line (35% vs. 66%, p<0001). CONCLUSIONS: Our data show that in a real-life setting availability of routine VL monitoring may not be exploited to its potential. A lack of timely follow-up after a first unsuppressed VL and reluctance to switch patients with confirmed virological failure, reduce the benefit of VL monitoring, i.e. in the rural clinics. Future studies will have to assess models of care which ensure that VL results are met with an action and make use of scalable innovative approaches.