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  • Emerging priorities for HIV service delivery

    Ford, N; Geng, E; Ellman, T; Orrell, C; Ehrenkranz, P; Sikazwe, I; Jahn, A; Rabkin, M; Ayisi Addo, S; Grimsrud, A; et al. (Public Library of Science, 2020-02-14)
    Nathan Ford and co-authors discuss global priorities in the provision of HIV prevention and treatment services.
  • Tailored HIV programmes and universal health coverage

    Holmes, CB; Rabkin, M; Ford, N; Preko, P; Rosen, S; Ellman, T; Ehrenkranz, P (World Health Organization, 2020-02-01)
    Improvements in geospatial health data and tailored human immunodeficiency virus (HIV) testing, prevention and treatment have led to greater microtargeting of the HIV response, based on location, risk, clinical status and disease burden. These approaches show promise for achieving control of the HIV epidemic. At the same time, United Nations Member States have committed to achieving broader health and development goals by 2030, including universal health coverage (UHC). HIV epidemic control will facilitate UHC by averting the need to commit ever-increasing resources to HIV services. Yet an overly targeted HIV response could also distort health systems, impede integration and potentially threaten broader health goals. We discuss current approaches to achieving both UHC and HIV epidemic control, noting potential areas of friction between disease-specific microtargeting and integrated health systems, and highlighting opportunities for convergence that could enhance both initiatives. Examples of these programmatic elements that could be better aligned include: improved information systems with unique identifiers to track and monitor individuals across health services and the life course; strengthened subnational data use; more accountable supply chains that supply a broad range of services; and strengthened community-based services and workforces. We argue that the response both to HIV and to broader health threats should use these areas of convergence to increase health systems efficiency and mitigate the harm of any potential decrease in health funding. Further investments in implementation and monitoring of these programme elements will be needed to make progress towards both UHC and HIV epidemic control.
  • HIV viral load algorithm

    Shroufi, A; van Cutsem, G; Phillips, A; Maman, D; Murphy, R; Duncan, K; Cambiano, V; Bansi-Matharu, L (Ovid Technologies (Wolters Kluwer Health), 2020-01)
    Letter to the Editor | No Abstract
  • Scaling up HIV viral load monitoring in Manicaland, Zimbabwe: challenges and opportunities from the field

    Nyagadza, B; Kudya, N; Mbofana, E; Masaka, S; Garone, D; Chen, CY; Mulingwa, A; Uzande, C; Isaakidis, P; Ndlovu, Z (International Union Against Tuberculosis and Lung Disease, 2019-12-21)
    Background: Demand for viral load (VL) monitoring is expected to increase; however, implementation of the multifaceted VL testing poses numerous challenges. We report experiences from Médecins Sans Frontiéres (MSF) and partners in the scale-up of HIV VL in collaboration with the Ministry of Health and Child Care (MoHCC) of Zimbabwe. Methods: A retrospective data review of routine reports from MSF-supported health facilities in Manicaland Province (Zimbabwe) was conducted. These secondary aggregate data were triangulated, and emerging themes of lessons learnt from VL monitoring were shared. Results: A VL testing coverage of 63% (5966/9456) was achieved among the 40 health facilities, together with a switch rate to second-line antiretroviral therapy (ART) of 46.4% (108/233). The key enablers to scaling-up the VL monitoring were well-equipped and supported VL laboratories, the operationalisation of the on-the-job clinical mentoring and systematic weaning off of better performing health facilities. Concerted efforts from different implementing partners and funders in the HIV programme, and close collaboration with MoHCC were pivotal. Conclusion: Our experience indicates that clinical mentoring is effective, and resulted in high VL testing coverage and up-skilling primary health care workers in VL monitoring. Attention must be focused on innovations for improving VL result utilisation, especially the identification and management of patients who fail ART.
  • Peer Mentorship via Mobile Phones for Newly Diagnosed HIV-Positive Youths in Clinic Care in Khayelitsha, South Africa: Mixed Methods Study

    Hacking, D; Cassidy, T; Mgengwana-Mbakaza, Z; Boulle, A; Mathys, R; Runeyi, P; Duran, L (JMIR Publications Inc., 2019-12-10)
    Background: Youths in South Africa are poor utilizers of HIV health services. Medecins Sans Frontieres has been piloting youth-adapted services at a youth clinic in Khayelitsha, including a peer virtual mentorship program over mobile phones, piloted from March 2015 to May 2016. Objective: The objective of this study was to evaluate the effect of the peer mentorship program on youth engagement with HIV services and explore the acceptability of the program to both mentors and mentees. Methods: Antiretroviral initiation, retention in care (RIC), and viral load suppression were compared between youths engaged in the virtual mentorship program and two matched controls. In-depth interviews were also conducted for 5 mentors and 5 mentees to explore acceptability and impact of the program. Results: A total of 40 youths were recruited into the virtual mentorship program over the study period. Of these, data were obtained for 35 and 2 matched controls were randomly sampled for each. There was no difference in baseline demographics (eg, age, gender, and CD4 count). Mentees had increased antiretroviral initiation (28/35, 80% vs 30/70, 42% in matched controls) and viral load completion (28/35, 80% vs 32/70, 45%); however, no differences were found in viral load suppression or RIC at 6 or 12 months. Mentors reported being motivated to participate in the program because of previous personal struggles with HIV and a desire to help their peers. Mentees reported fears of disclosure and lack of acceptance of their status as barrier to accessing services, but they felt free to talk to their mentors, valued the mentorship program, and indicated a preference for phone calls. Conclusions: Peer mentorship in youths is acceptable to both mentors and mentees and appears to increase linkage to care and viral load completion rates.
  • Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression

    Musinguzi, N; Castillo-Mancilla, J; Morrow, M; Byakwaga, H; Mawhinney, S; Burdo, TH; Boum, Y; Muzoora, C; Bwana, BM; Siedner, MJ; et al. (Lippincott, Williams & Wilkins, 2019-12-01)
    Background: Residual systemic inflammation, which is associated with non-AIDS clinical outcomes, may persist despite viral suppression. We assessed the effect of antiretroviral therapy (ART) adherence interruptions on systemic inflammation among Ugandans living with HIV who were virally suppressed. Setting: We evaluated adults initiating first-line ART at a regional referral hospital clinic in Mbarara, Uganda. Methods: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble sCD14, sCD163, the kynurenine/tryptophan (K/T) ratio, and CD8+ T-cell activation (HLA-DR+/CD38+ coexpression) were measured at baseline and 6 months after ART initiation among participants who achieved viral suppression (<400 copies/mL) at 6 months. ART adherence was monitored electronically. Time spent in an adherence interruption was computed as the percentage of days when the running average adherence was ≤10%. We fit adjusted linear regressions to evaluate the effect of time spent in an interruption on the log-transformed plasma concentrations of the inflammation biomarkers. Results: Of 282 participants, 70% were women, and the median age was 34 years. At baseline, median CD4 and median log viral load were 135 cells per microliter and 5.1 copies per milliliter, respectively. In the adjusted analysis, a running average adherence of <10% was associated with higher sCD14 (+3%; P < 0.008), sCD163 (+5%; P = 0.002), D-dimer (+10%; P = 0.007), HLA-DR+/CD8+ (+3%; P < 0.025), IL-6 (+14%; P = 0.008), and K:T ratio (+5%; P = 0.002). These findings were largely robust to adjustment for average adherence, as well as higher thresholds of running average adherence, albeit with decreased statistical significance. Conclusions: Increased time spent in adherence interruptions is associated with increased levels of inflammation, despite viral suppression above and beyond average adherence.
  • Refused and referred-persistent stigma and discrimination against people living with HIV/AIDS in Bihar: a qualitative study from India

    Nair, M; Kumar, P; Harshana, A; Kazmi, S; Pandey, S; Burza, S; Moreto-Planas, L (British Medical Journal BMJ, 2019-11-25)
    OBJECTIVES: This study aimed to explore barriers to accessing care, if any, among people living with HIV/AIDS (PLHA) in two districts of Bihar. We also aimed to assess attitudes towards PLHA among healthcare providers and community members. DESIGN: This qualitative study used an exploratory study design through thematic analysis of semistructured, in-depth interviews. SETTING: Two districts were purposively selected for the study, namely the capital Patna and a peripheral district located approximately 100 km from Patna, in order to glean insights from a diverse sample of respondents. PARTICIPANTS: Our team purposively selected 71 participants, including 35 PLHA, 10 community members and 26 healthcare providers. RESULTS: The overarching theme that evolved from these data through thematic coding identified that enacted stigma and discrimination interfere with each step in the HIV care continuum for PLHA in Bihar, India, especially outside urban areas. The five themes that contributed to these results include: perception of HIV as a dirty illness at the community level; non-consensual disclosure of HIV status; reliance on identifying PLHA to guide procedures and resistance to universal precautions; refusal to treat identified PLHA and referrals to other health centres for treatment; and inadequate knowledge and fear among health providers with respect to HIV transmission. CONCLUSIONS: The continued presence of discriminatory and stigmatising attitudes towards PLHA negatively impacts both disclosure of HIV status as well as access to care and treatment. We recognise a pressing need to improve the knowledge of HIV transmission, and implement universal precautions across all health facilities in the state, not just to reduce stigma and discrimination but also to ensure proper infection control. In order to improve treatment adherence and encourage optimal utilisation of services, it is imperative that the health system invest more in stigma reduction in Bihar and move beyond more ineffective, punitive approaches.
  • Genotyping and outcomes of presumptive second line ART failure cases switched to third line or maintained on second line ART in Mumbai, India

    Gill, N; Van den Bergh, R; Wut Yee Kyaw, K; Laxmeshwar, C; Das, M; Rastogi, S; Mansoor, H; Kalon, S; Isaakidis, P; Arago Galindo, M (2019-11-21)
    BACKGROUND: HIV programs are increasingly confronted with failing antiretroviral therapy (ART), including second-line regimens. WHO has provided guidelines on switching to third-line ART. In a Médecins Sans Frontières clinic in Mumbai, India, receiving referred presumptive second-line ART failure cases, an evidence-based protocol consisting of viral load (VL) testing, enhanced adherence counselling (EAC) and genotype for switching was implemented. OBJECTIVE: To document the outcome and genotype of presumptive second-line ART failure cases switched to third-line or maintained on second-line ART. DESIGN: Retrospective cohort study of patients referred between January 2011 and September 2017. RESULTS: The cases (n = 120) were complex with median 9.2 years of ART exposure, poor adherence at baseline, and exposure to multiple ART regimens other than recommended by WHO. Out of 90 evaluated cases, 39(43%) were maintained on second-line ART. Forty-nine (54%) were ever switched to third-line ART. Twelve months virological suppression was 72% in the second-line and 93% in the third-line ART cohort, while retention in care was 80% and 94% respectively. Genotyping showed 62% resistance for PIs, and 52% triple class resistance to NRTIs, NNRTIs and PIs. Resistance was noted for the new class of integrase inhibitors, and for different drugs without any documented previous exposure to the same drug. CONCLUSION: Adopting WHO guidelines on switching ART regimens and provision of EAC can prevent unnecessary switching/exposure to third-line ART regimens. Genotyping is urgently required in national HIV programs, which currently use only the exposure history of patients for switching to third-line ART regimens.
  • What drives mortality among HIV patients in a conflict setting? A prospective cohort study in the Central African Republic

    Crellen, T; Ssonko, C; Piening, T; Simaleko, MM; Geiger, K; Siddiqui, MR (2019-11-14)
    BACKGROUND: Provision of antiretroviral therapy (ART) during conflict settings is rarely attempted and little is known about the expected patterns of mortality. The Central African Republic (CAR) continues to have a low coverage of ART despite an estimated 110,000 people living with HIV and 5000 AIDS-related deaths in 2018. We present results from a cohort in Zemio, Haut-Mboumou prefecture. This region had the highest prevalence of HIV nationally (14.8% in a 2010 survey), and was subject to repeated attacks by armed groups on civilians during the observed period. METHODS: Conflict from armed groups can impact cohort mortality rates i) directly if HIV patients are victims of armed conflict, or ii) indirectly if population displacement or fear of movement reduces access to ART. Using monthly counts of civilian deaths, injuries and abductions, we estimated the impact of the conflict on patient mortality. We also determined patient-level risk factors for mortality and how the risk of mortality varies with time spent in the cohort. Model-fitting was performed in a Bayesian framework, using logistic regression with terms accounting for temporal autocorrelation. RESULTS: Patients were recruited and observed in the HIV treatment program from October 2011 to May 2017. Overall 1631 patients were enrolled and 1628 were included in the analysis giving 48,430 person-months at risk and 145 deaths. The crude mortality rate after 12 months was 0.92 (95% CI 0.90, 0.93). Our model showed that patient mortality did not increase during periods of heightened conflict; the odds ratios (OR) 95% credible interval (CrI) for i) civilian fatalities and injuries, and ii) civilian abductions on patient mortality both spanned unity. The risk of mortality for individual patients was highest in the second month after entering the cohort, and declined seven-fold over the first 12 months. Male sex was associated with a higher mortality (odds ratio 1.70 [95% CrI 1.20, 2.33]) along with the severity of opportunistic infections (OIs) at baseline (OR 2.52; 95% CrI 2.01, 3.23 for stage 2 OIs compared with stage 1). CONCLUSIONS: Our results show that chronic conflict did not appear to adversely affect rates of mortality in this cohort, and that mortality was driven predominantly by patient-specific risk factors. The risk of mortality and recovery of CD4 T-cell counts observed in this conflict setting are comparable to those in stable resource poor settings, suggesting that conflict should not be a barrier in access to ART.
  • Distribution of advanced HIV disease from three high HIV prevalence settings in Sub-Saharan Africa: a secondary analysis data from three population-based cross-sectional surveys in Eshowe (South Africa), Ndhiwa (Kenya) and Chiradzulu (Malawi)

    Chihana, ML; Huerga, H; Van Cutsem, G; Ellman, T; Goemaere, E; Waniala, S; Masiku, C; Szumilin, E; Etard, JF; Maman, D; et al. (Taylor & Francis, 2019-11-04)
    Background: Despite substantial progress in antiretroviral therapy (ART) scale up, some people living with HIV (PLHIV) continue to present with advanced HIV disease, contributing to ongoing HIV-related morbidity and mortality. Objective: We aimed to quantify population-level estimates of advanced HIV from three high HIV prevalence settings in Sub-Saharan Africa. Methods: Three cross-sectional surveys were conducted in (Ndhiwa (Kenya): September–November 2012), (Chiradzulu (Malawi): February–May 2013) and (Eshowe (South Africa): July–October 2013). Eligible individuals 15–59 years old who consented were interviewed at home followed by rapid HIV test and CD4 count test if tested HIV-positive. Advanced HIV was defined as CD4 < 200 cells/µl. We used logistic regression to identify patient characteristics associated with advanced HIV. Results: Among 18,991 (39.2% male) individuals, 4113 (21.7%) tested HIV-positive; 385/3957 (9.7% (95% Confidence Interval [CI]: 8.8–10.7)) had advanced HIV, ranging from 7.8% (95%CI 6.4–9.5) Chiradzulu (Malawi) to 11.8% (95%CI 9.8–14.2) Ndhiwa (Kenya). The proportion of PLHIV with advanced disease was higher among men 15.3% (95% CI 13.2–17.5) than women 7.5% (95%CI 6.6–8.6) p < 0.001. Overall, 62.7% of all individuals with advanced HIV were aware of their HIV status and 40.3% were currently on ART. Overall, 65.6% of individuals not on ART had not previously been diagnosed with HIV, while only 29.6% of those on ART had been on ART for ≥6 months. Individuals with advanced HIV disease were more likely to be men (adjusted Odds Ratio [aOR]; 2.1 (95%CI 1.7–2.6), and more likely not to be on ART (aOR; 1.7 (95%CI 1.3–2.1). Conclusion: In our study, about 1 in 10 PLHIV had advanced HIV with nearly 40% of them unaware of their HIV status. However, a substantial proportion of patients with advanced HIV were established on ART. Our findings suggest the need for a dual focus on alternative testing strategies to identify PLHIV earlier as well as improving ART retention.
  • Feasibility of antiretroviral therapy initiation under the treat‐all policy under routine conditions: a prospective cohort study from Eswatini

    Kerschberger, B; Jobanputra, K; Schomaker, M; Kabore, SM; Teck, R; Mabhena, E; Lukhele, N; Rusch, B; Boulle, A; Ciglenecki, I (Wiley Open Access, 2019-10-24)
    Introduction The World Health Organization recommends the Treat‐All policy of immediate antiretroviral therapy (ART) initiation, but questions persist about its feasibility in resource‐poor settings. We assessed the feasibility of Treat‐All compared with standard of care (SOC) under routine conditions. Methods This prospective cohort study from southern Eswatini followed adults from HIV care enrolment to ART initiation. Between October 2014 and March 2016, Treat‐All was offered in one health zone and SOC according to the CD4 350 and 500 cells/mm3 treatment eligibility thresholds in the neighbouring health zone, each of which comprised one secondary and eight primary care facilities. We used Kaplan–Meier estimates, multivariate flexible parametric survival models and standardized survival curves to compare ART initiation between the two interventions. Results Of the 1726 (57.3%) patients enrolled under Treat‐All and 1287 (42.7%) under SOC, cumulative three‐month ART initiation was higher under Treat‐All (91%) than SOC (74%; p < 0.001) with a median time to ART of 1 (IQR 0 to 14) and 10 (IQR 2 to 117) days respectively. Under Treat‐All, ART initiation was higher in pregnant women (vs. non‐pregnant women: adjusted hazard ratio (aHR) 1.96, 95% confidence interval (CI) 1.70 to 2.26), those with secondary education (vs. no formal education: aHR 1.48, 95% CI 1.12 to 1.95), and patients with an HIV‐positive diagnosis before care enrolment (aHR 1.22, 95% CI 1.10 to 1.36). ART initiation was lower in patients attending secondary care facilities (aHR 0.64, 95% CI 0.58 to 0.72) and for CD4 351 to 500 when compared with CD4 201 to 350 cells/mm3 (aHR 0.84, 95% CI 0.72 to 1.00). ART initiation varied over time for TB cases, with lower hazard during the first two weeks after HIV care enrolment and higher hazards thereafter. Of patients with advanced HIV disease (n = 1085; 36.0%), crude 3‐month ART initiation was similar in both interventions (91% to 92%) although Treat‐All initiated patients more quickly during the first month after HIV care enrolment. Conclusions ART initiation was high under Treat‐All and without evidence of de‐prioritization of patients with advanced HIV disease. Additional studies are needed to understand the long‐term impact of Treat‐All on patient outcomes.
  • Field Suitability and Diagnostic Accuracy of the Biocentric Open Real-Time PCR Platform for Dried Blood Spot-Based HIV Viral Load Quantification in Eswatini.

    Kerschberger, B; Ntshalintshali, N; Mpala, Q; Diaz Uribe, PA; Maphalala, G; Kalombola, S; Telila, AB; Chawinga, T; Maphalala, M; Jani, A; et al. (Lippincott, Williams & Wilkins, 2019-09-01)
    BACKGROUND: To assess the performance and suitability of dried blood spot (DBS) sampling using filter paper to collect blood for viral load (VL) quantification under routine conditions. METHODS: We compared performance of DBS VL quantification using the Biocentric method with plasma VL quantification using Roche and Biocentric as reference methods. Adults (≥18 years) were enrolled at 2 health facilities in Eswatini from October 12, 2016 to March 1, 2017. DBS samples were prepared through finger-prick by a phlebotomist (DBS-1), and through the pipetting of whole venous blood by a phlebotomist (DBS-2) and by a laboratory technologist (DBS-3). We calculated the VL-testing completion rate, correlation, and agreement, as well as diagnostic accuracy estimates at the clinical threshold of 1000 copies/mL. RESULTS: Of 362 patients enrolled, 1066 DBS cards (DBS-1: 347; DBS-2: 359; DBS-3: 360) were tested. Overall, test characteristics were comparable between DBS-sampling methods, irrespective of the reference method. The Pearson correlation coefficients ranged from 0.67 to 0.82 (P < 0.001) for different types of DBS sampling using both reference methods, and the Bland-Altman difference ranged from 0.15 to 0.30 log10 copies/mL. Sensitivity estimates were from 85.3% to 89.2% and specificity estimates were from 94.5% to 98.6%. The positive predictive values were between 87.0% and 96.5% at a prevalence of 30% VL elevations, and negative predictive values were between 93.7% and 95.4%. CONCLUSIONS: DBS VL quantification using the newly configured Biocentric method can be part of contextualized VL-testing strategies, particularly for remote settings and populations with higher viral failure rates.
  • Point-of-care viral load monitoring: outcomes from a decentralized HIV programme in Malawi.

    Nicholas, S; Poulet, E; Wolters, L; Wapling, J; Rakesh, A; Amoros, I; Szumilin, E; Gueguen, M; Schramm, B (John Wiley & Sons, 2019-08-01)
    INTRODUCTION: Routinely monitoring the HIV viral load (VL) of people living with HIV (PLHIV) on anti-retroviral therapy (ART) facilitates intensive adherence counselling and faster ART regimen switch when treatment failure is indicated. Yet standard VL-testing in centralized laboratories can be time-intensive and logistically difficult in low-resource settings. This paper evaluates the outcomes of the first four years of routine VL-monitoring using Point-of-Care technology, implemented by Médecins Sans Frontières (MSF) in rural clinics in Malawi. METHODS: We conducted a retrospective cohort analysis of patients eligible for routine VL- testing between 2013 and 2017 in four decentralized ART-clinics and the district hospital in Chiradzulu, Malawi. We assessed VL-testing coverage and the treatment failure cascade (from suspected failure (first VL>1000 copies/mL) to VL suppression post regimen switch). We used descriptive statistics and multivariate logistic regression to assess factors associated with suspected failure. RESULTS AND DISCUSSION: Among 21,400 eligible patients, VL-testing coverage was 85% and VL suppression was found in 89% of those tested. In the decentralized clinics, 88% of test results were reviewed on the same day as blood collection, whereas in the district hospital the median turnaround-time for results was 85 days. Among first-line ART patients with suspected failure (N = 1544), 30% suppressed (VL<1000 copies/mL), 35% were treatment failures (confirmed by subsequent VL-testing) and 35% had incomplete VL follow-up. Among treatment failures, 80% (N = 540) were switched to a second-line regimen, with a higher switching rate in the decentralized clinics than in the district hospital (86% vs. 67%, p < 0.01) and a shorter median time-to-switch (6.8 months vs. 9.7 months, p < 0.01). Similarly, the post-switch VL-testing rate was markedly higher in the decentralized clinics (61% vs. 26%, p < 0.01). Overall, 79% of patients with a post-switch VL-test were suppressed. CONCLUSIONS: Viral load testing at the point-of-care in Chiradzulu, Malawi achieved high coverage and good drug regimen switch rates among those identified as treatment failures. In decentralized clinics, same-day test results and shorter time-to-switch illustrated the game-changing potential of POC-based VL-testing. Nevertheless, gaps were identified along all steps of the failure cascade. Regular staff training, continuous monitoring and creating demand are essential to the success of routine VL-testing.
  • Simplifying switch to second-line antiretroviral therapy in sub Saharan Africa: predicted effect of using a single viral load to define efavirenz-based first-line failure.

    Shroufi, A; Van Cutsem, G; Cambiano, V; Bansi-Matharu, L; Duncan, K; Murphy, RA; Maman, D; Phillips, A (Wolters Kluwer Health/Lippincott Williams & Wilkins, 2019-08-01)
    BACKGROUND: Many individuals failing first-line antiretroviral therapy (ART) in sub-Saharan Africa never initiate second-line ART or do so after significant delay. For people on ART with a viral load more than 1000 copies/ml, the WHO recommends a second viral load measurement 3 months after the first viral load and enhanced adherence support. Switch to a second-line regimen is contingent upon a persistently elevated viral load more than 1000 copies/ml. Delayed second-line switch places patients at increased risk for opportunistic infections and mortality. METHODS: To assess the potential benefits of a simplified second-line ART switch strategy, we use an individual-based model of HIV transmission, progression and the effect of ART which incorporates consideration of adherence and drug resistance, to compare predicted outcomes of two policies, defining first-line regimen failure for patients on efavirenz-based ART as either two consecutive viral load values more than 1000 copies/ml, with the second after an enhanced adherence intervention (implemented as per current WHO guidelines) or a single viral load value more than 1000 copies/ml. We simulated a range of setting-scenarios reflecting the breadth of the sub-Saharan African HIV epidemic, taking into account potential delays in defining failure and switch to second-line ART. FINDINGS: The use of a single viral load more than 1000 copies/ml to define ART failure would lead to a higher proportion of persons with nonnucleoside reverse-transcriptase inhibitor resistance switched to second-line ART [65 vs. 48%; difference 17% (90% range 14-20%)], resulting in a median 18% reduction in the rate of AIDS-related death over setting scenarios (90% range 6-30%; from a median of 3.1 to 2.5 per 100 person-years) over 3 years. The simplified strategy also is predicted to reduce the rate of AIDS conditions by a median of 31% (90% range 8-49%) among people on first-line ART with a viral load more than 1000 copies/ml in the past 6 months. For a country of 10 million adults (and a median of 880 000 people with HIV), we estimate that this approach would lead to a median of 1322 (90% range 67-3513) AIDS deaths averted per year over 3 years. For South Africa this would represent around 10 215 deaths averted annually. INTERPRETATION: As a step towards reducing unnecessary mortality associated with delayed second-line ART switch, defining failure of first-line efavirenz-based regimens as a single viral load more than 1000 copies/ml should be considered.
  • A cluster randomized controlled trial of extending ART refill intervals to six-monthly for anti-retroviral adherence clubs.

    Wilkinson, L; Grimsrud, A; Cassidy, T; Orrell, C; Voget, J; Hayes, H; Keene, C; Steele, SJ; Gerstenhaber, R (BioMed Central, 2019-07-30)
    BACKGROUND: The antiretroviral therapy (ART) adherence club (AC) differentiated service delivery model, where clinically stable ART patients receive their ART refills and psychosocial support in groups has supported clinically stable patients' retention and viral suppression. Patients and health systems could benefit further by reducing visit frequency and increasing ART refills. We designed a cluster-randomized control trial comparing standard of care (SoC) ACs and six-month ART refill (Intervention) ACs in a large primary care facility in Khayelitsha, South Africa. METHODS: Existing ACs were randomized to either the control (SOC ACs) or intervention (Intervention ACs) arm. SoC ACs meet five times annually, receiving two-month ART refills with a four-month ART refill over year-end. Blood is drawn at the AC visit ahead of the clinical assessment visit. Intervention ACs meet twice annually receiving six-month ART refills, with a third individual visit for routine blood collection anytime two-four weeks before the annual clinical assessment AC visit. Primary outcomes will be retention in care, annual viral load assessment completion and viral load suppression. (<400copies/mL) after 2 years. Ethics approval has been granted by the University of Cape Town (HREC 652/2016) and the Medecins Sans Frontieres (MSF) Ethics Review Board (#1639). Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents. DISCUSSION: Evaluation of an extended ART refill interval in adherence clubs will provide evidence towards novel model adaptions that can be made to further improve convenience for patients and leverage health system efficiencies.
  • Decreased risk of HIV-associated TB during antiretroviral therapy expansion in rural Eswatini from 2009 to 2016: a cohort and population-based analysis

    Kerschberger, B; Schomaker, M; Telnov, A; Vambe, D; Kisyeri, N; Sikhondze, W; Pasipamire, L; Ngwenya, SM; Rusch, B; Ciglenecki, I; et al. (John Wiley & Sons, 2019-07-16)
    This paper assesses patient- and population-level trends in TB notifications during rapid expansion of antiretroviral therapy in Eswatini which has an extremely high incidence of both TB and HIV. METHODS: Patient- and population-level predictors and rates of HIV-associated TB were examined in the Shiselweni region in Eswatini from 2009 to 2016. Annual population-level denominators obtained from projected census data and prevalence estimates obtained from population-based surveys were combined with individual-level TB treatment data. Patient- and population-level predictors of HIV-associated TB were assessed with multivariate logistic and multivariate negative binomial regression models. RESULTS: Of 11 328 TB cases, 71.4% were HIV co-infected and 51.8% were women. TB notifications decreased fivefold between 2009 and 2016, from 1341 to 269 cases per 100 000 person-years. The decline was sixfold in PLHIV vs. threefold in the HIV-negative population. Main patient-level predictors of HIV-associated TB were recurrent TB treatment (adjusted odds ratio [aOR] 1.40, 95% confidence interval [CI]: 1.19-1.65), negative (aOR 1.31, 1.15-1.49) and missing (aOR 1.30, 1.11-1.53) bacteriological status and diagnosis at secondary healthcare level (aOR 1.18, 1.06-1.33). Compared with 2009, the probability of TB decreased for all years from 2011 (aOR 0.69, 0.58-0.83) to 2016 (aOR 0.54, 0.43-0.69). The most pronounced population-level predictor of TB was HIV-positive status (adjusted incidence risk ratio 19.47, 14.89-25.46). CONCLUSIONS: This high HIV-TB prevalence setting experienced a rapid decline in TB notifications, most pronounced in PLHIV. Achievements in HIV-TB programming were likely contributing factors.
  • Performance of cepheid GeneXpert HIV-1 viral load plasma assay to accurately detect treatment failure: a clinical meta-analysis

    Sacks, JA; Fong, Y; Gonzalez, MP; Andreotti, M; Baliga, S; Garrett, N; Jordan, J; Karita, E; Kulkarni, S; Mor, O; et al. (Wolters Kluwer Health / Lippincott Williams & Wilkins, 2019-07-02)
    Background: Coverage of viral load testing remains low with only half of the patients in need having adequate access. Alternative technologies to high throughput centralized machines can be used to support viral load scale-up; however, clinical performance data are lacking. We conducted a meta-analysis comparing the Cepheid Xpert HIV-1 viral load plasma assay to traditional laboratory-based technologies. Methods: Cepheid Xpert HIV-1 and comparator laboratory technology plasma viral load results were provided from 13 of the 19 eligible studies, which accounted for a total of 3790 paired data points. We used random effects models to determine the accuracy and misclassification at various treatment failure thresholds (detectable, 200, 400, 500, 600, 800 and 1000 copies/ml). Results: Thirty percent of viral load test results were undetectable, while 45% were between detectable and 10 000 copies/ml and the remaining 25% were above 10 000 copies/ml. The median Xpert viral load was 119 copies/ml and the median comparator viral load was 157 copies/ml, while the log10 bias was 0.04 (0.02–0.07). The sensitivity and specificity to detect treatment failure were above 95% at all treatment failure thresholds, except for detectable, at which the sensitivity was 93.33% (95% confidence interval: 88.2–96.3) and specificity was 80.56% (95% CI: 64.6–90.4). Conclusion: The Cepheid Xpert HIV-1 viral load plasma assay results were highly comparable to laboratory-based technologies with limited bias and high sensitivity and specificity to detect treatment failure. Alternative specimen types and technologies that enable decentralized testing services can be considered to expand access to viral load.
  • Patient experiences of ART adherence clubs in Khayelitsha and Gugulethu, Cape Town, South Africa: A qualitative study.

    Venables, E; Towriss, C; Rini, Z; Nxiba, X; Cassidy, T; Tutu, S; Grimsrud, A; Myer, L; Wilkinson, L (Public Library of Science, 2019-06-20)
    BACKGROUND: Globally, 37 million people are in need of lifelong antiretroviral treatment (ART). With the continual increase in the number of people living with HIV starting ART and the need for life-long retention and adherence, increasing attention is being paid to differentiated service delivery (DSD), such as adherence clubs. Adherence clubs are groups of 25-30 stable ART patients who meet five times per year at their clinic or a community location and are facilitated by a lay health-care worker who distributes pre-packed ART. This qualitative study explores patient experiences of clubs in two sites in Cape Town, South Africa. METHODS: A total of 144 participants took part in 11 focus group discussions (FGDs) and 56 in-depth interviews in the informal settlements of Khayelitsha and Gugulethu in Cape Town, South Africa. Participants included current club members, stable patients who had never joined a club and club members referred back to clinician-led facility-based standard care. FGDs and interviews were conducted in isiXhosa, translated and transcribed into English, entered into NVivo, coded and thematically analysed. RESULTS: The main themes were 1) understanding and knowledge of clubs; 2) understanding of and barriers to enrolment; 3) perceived benefits and 4) perceived disadvantages of the clubs. Participants viewed membership as an achievement and considered returning to clinician-led care a 'failure'. Moving between clubs and the clinic created frustration and broke down trust in the health-care system. CONCLUSIONS: Adherence clubs were appreciated by patients, particularly time-saving in relation to flexible ART collection. Improved patient understanding of enrolment processes, eligibility and referral criteria and the role of clinical oversight is essential for building relationships with health-care workers and trust in the health-care system.
  • "I take my pills every day, but then it goes up, goes down. I don't know what's going on": Perceptions of HIV virological failure in a rural context in Mozambique. A qualitative research study.

    Pulido Tarquino, IA; Venables, E; de Amaral Fidelis, JM; Giuliani, R; Decroo, T (Public Library of Science, 2019-06-17)
    BACKGROUND: HIV prevalence in Mozambique is estimated to be 13.2%. Routine viral load for HIV monitoring was first implemented in the rural area of Tete in 2014. Programmatic data showed an unexpected high proportion of high viral load results, with up to 40% of patients having a viral load above 1000 copies/ml. OBJECTIVES: This qualitative study aimed to explore perceptions about virological failure and viral load monitoring from the perspective of HIV positive patients on first-line antiretroviral therapy (ART) and health-care workers. METHODS: The study was conducted in seven rural communities in Changara-Marara district, Tete province, Mozambique. A total of 91 participants took part in in-depth interviews (IDIs) and focus group discussions (FGDs), including health-care workers (n = 18), patients on ART in individual care or Community Adherence Groups (CAGs) who experienced virological failure and virological re-suppression (n = 39) and CAG focal points (n = 34). Purposive sampling was used to select participants. Interviews and FGDs were conducted in Nhuengue and Portuguese. IDIs and FGDs were translated and transcribed before being coded and thematically analysed. RESULTS: Emergent themes showed that patients and health-care workers attributed great importance to viral load monitoring. A supressed viral load was viewed by participants as a predictor of good health and good adherence. However, some patients were confused and appeared distressed when confronted with virological failure. Viral load results were often little understood, especially when virological failure was detected despite good adherence. Inadequate explanations of causes of virological failure, delayed follow-up viral load results, repeated blood tests and lack of access to second-line ART resulted in reduced confidence in the effectiveness of ART, challenged the patient-provider relationship and disempowered patients and providers. CONCLUSION: In this rural context undetectable viral load is recognized as a predictor of good health by people living with HIV and health-care workers. However, a lack of knowledge and health system barriers caused different responses in patients and health-care workers. Adapted counselling strategies, accelerated viral load follow-up and second-line ART initiation in patients with virological failure need to be prioritized.
  • Routine immediate eye examination at the point of care for diagnosis of AIDS-related Cytomegalovirus Retinitis among patients with a CD4-count < 100 in Myanmar

    Ei, WLSS; Soe, KP; Hilbig, A; Murray, J; Heiden, D (Oxford University Press, 2019-06-14)
    A retrospective review of diagnosis of cytomegalovirus retinitis (CMVR) before and after introduction of routine immediate eye examination among AIDS patient in Myanmar with an absolute CD4 T cell count <100 cells/microliter demonstrated an increased detection of CMVR from 1.1% (14/1233) to 10.7% (65/608), an improvement of approximately ten-fold. Diagnosis of CMVR was achieved a mean of 2 days after clinic enrollment.

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