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  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Outcomes of patients enrolled in an antiretroviral adherence club with recent viral suppression after experiencing elevated viral loads

    Sharp, J; Wilkinson, L; Cox, V; Cragg, C; van Custem, G; Grimsrud, A (Health and Medical Publishing Group, 2019-06-11)
    Background: Eligibility for differentiated antiretroviral therapy (ART) delivery models has to date been limited to low-risk stable patients. Objectives: We examined the outcomes of patients who accessed their care and treatment through an ART adherence club (AC), a differentiated ART delivery model, immediately following receiving support to achieve viral suppression after experiencing elevated viral loads (VLs) at a high-burden ART clinic in Khayelitsha, South Africa. Methods: Beginning in February 2012, patients with VLs above 400 copies/mL either on firstor second-line regimens received a structured intervention developed for patients at risk of treatment failure. Patients who successfully suppressed either on the same regimen or after regimen switch were offered immediate enrolment in an AC facilitated by a lay community health worker. We conducted a retrospective cohort analysis of patients who enrolled in an AC directly after receiving suppression support. We analysed outcomes (retention in care, retention in AC care and viral rebound) using Kaplan–Meier methods with follow-up from October 2012 to June 2015. Results: A total of 165 patients were enrolled in an AC following suppression (81.8% female, median age 36.2 years). At the closure of the study, 119 patients (72.0%) were virally suppressed and 148 patients (89.0%) were retained in care. Six, 12 and 18 months after AC enrolment, retention in care was estimated at 98.0%, 95.0% and 89.0%, respectively. Viral suppression was estimated to be maintained by 90.0%, 84.0% and 75.0% of patients at 6, 12 and 18 months after AC enrolment, respectively. Conclusion: Our findings suggest that patients who struggled to achieve or maintain viral suppression in routine clinic care can have good retention and viral suppression outcomes in ACs, a differentiated ART delivery model, following suppression support.
  • Investigating the addition of oral HIV self-tests among populations with high testing coverage - Do they add value? Lessons from a study in Khayelitsha, South Africa.

    Moore, HA; Metcalf, CA; Cassidy, T; Hacking, D; Shroufi, A; Steele, SJ; Duran, LT; Ellman, T (Public Library of Science, 2019-05-02)
    INTRODUCTION: HIV self-testing (HIVST) offers a useful addition to HIV testing services and enables individuals to test privately. Despite recommendations to the contrary, repeat HIV testing is frequent among people already on anti-retroviral treatment (ART) and there are concerns that oral self-testing might lead to false negative results. A study was conducted in Khayelitsha, South Africa, to assess feasibility and uptake of HIVST and linkage-to-care following HIVST. METHODS: Participants were recruited at two health facilities from 1 March 2016 to 31 March 2017. People under 18 years, or with self-reported previously-diagnosed HIV infection, were excluded. Participants received an OraQuick Rapid HIV-1/2 Antibody kit, and reported their HIVST results by pre-paid text message (SMS) or by returning to the facility. Those not reporting within 7 days were contacted by phone. Electronic and paper-based clinical and laboratory records were retrospectively examined for all participants to identify known HIV outcomes, after matching for name, date of birth, and sex. These findings were compared with self-reported HIVST results where available. RESULTS: Of 639 participants, 401 (62.8%) self-reported a negative HIVST result, 27 (4.2%) a positive result, and 211 (33.0%) did not report. The record search identified that of the 401 participants self-reporting a negative HIVST result, 19 (4.7%) were already known to be HIV positive; of the 27 self-reporting positive, 12 (44%) were known HIV positive. Overall, records showed 57/639 (8.9%) were HIV positive of whom 39/57 (68.4%) had previously-diagnosed infection and 18/57 (31.6%) newly-diagnosed infection. Of the 428 participants who self-reported a result, 366 (85.5%) reported by SMS. CONCLUSIONS: HIVST can improve HIV testing uptake and linkage to care. SMS is acceptable for reporting HIVST results but negative self-reports by participants may be unreliable. Use of HIVST by individuals on ART is frequent despite recommendations to the contrary and its implications need further consideration.
  • Diagnostic value of the urine lipoarabinomannan assay in HIV-positive, ambulatory patients with CD4 below 200 cells/μl in 2 low-resource settings: A prospective observational study.

    Huerga, H; Mathabire Rucker, SC; Cossa, L; Bastard, M; Amoros, I; Manhica, I; Mbendera, K; Telnov, A; Szumilin, E; Sanchez-Padilla, E; et al. (Public Library of Science, 2019-04-30)
    BACKGROUND: Current guidelines recommend the use of the lateral flow urine lipoarabinomannan assay (LAM) in HIV-positive, ambulatory patients with signs and symptoms of tuberculosis (TB) only if they are seriously ill or have CD4 count ≤ 100 cells/μl. We assessed the diagnostic yield of including LAM in TB diagnostic algorithms in HIV-positive, ambulatory patients with CD4 < 200 cells/μl, as well as the risk of mortality in LAM-positive patients who were not diagnosed using other diagnostic tools and not treated for TB. METHODS AND FINDINGS: We conducted a prospective observational study including HIV-positive adult patients with signs and symptoms of TB and CD4 < 200 cells/μl attending 6 health facilities in Malawi and Mozambique. Patients were included consecutively from 18 September 2015 to 27 October 2016 in Malawi and from 3 December 2014 to 22 August 2016 in Mozambique. All patients had a clinical exam and LAM, chest X-ray, sputum microscopy, and Xpert MTB/RIF assay (Xpert) requested. Culture in sputum was done for a subset of patients. The diagnostic yield was defined as the proportion of patients with a positive assay result among those with laboratory-confirmed TB. For the 456 patients included in the study, the median age was 36 years (IQR 31-43) and the median CD4 count was 50 cells/μl (IQR 21-108). Forty-five percent (205/456) of the patients had laboratory-confirmed TB. The diagnostic yields of LAM, microscopy, and Xpert were 82.4% (169/205), 33.7% (69/205), and 40.0% (84/205), respectively. In total, 50.2% (103/205) of the patients with laboratory-confirmed TB were diagnosed only through LAM. Overall, the use of LAM in diagnostic algorithms increased the yield of algorithms with microscopy and with Xpert by 38.0% (78/205) and 34.6% (71/205), respectively, and, specifically among patients with CD4 100-199 cells/μl, by 27.5% (14/51) and 29.4% (15/51), respectively. LAM-positive patients not diagnosed through other tools and not treated for TB had a significantly higher risk of mortality than LAM-positive patients who received treatment (adjusted risk ratio 2.57, 95% CI 1.27-5.19, p = 0.009). Although the TB diagnostic conditions in the study sites were similar to those in other resource-limited settings, the added value of LAM may depend on the availability of microscopy or Xpert results. CONCLUSIONS: LAM has diagnostic value for identifying TB in HIV-positive patients with signs and symptoms of TB and advanced immunodeficiency, including those with a CD4 count of 100-199 cells/μl. In this study, the use of LAM enabled the diagnosis of TB in half of the patients with confirmed TB disease; without LAM, these patients would have been missed. The rapid identification and treatment of TB enabled by LAM may decrease overall mortality risk for these patients.
  • Simplifying switch to second line ART: Predicted effect of defining failure of first-line efavirenz-based regimens in sub-Saharan Africa by a single viral load > 1000 copies/ml.

    Shroufi, A; Van Custem, G; Cambiano, V; Bansi-Matharu, L; Duncan, K; Murphy, RA; Maman, D; Phillips, A (Wolters Kluwer Health, 2019-04-16)
    BACKGROUND: Many individuals failing first-line antiretroviral therapy (ART) in sub-Saharan Africa never initiate second-line antiretroviral treatment (ART) or do so after significant delay. For people on ART with a viral load (VL) > 1000 copies/ml, the World Health Organization (WHO) recommends a second VL measurement 3 months after the first VL and enhanced adherence support. Switch to a second-line regimen is contingent upon a persistently elevated VL > 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 2 policies, defining 1st-line regimen failure for patients on efavirenz based ART as either (i) two consecutive VL values > 1000 copies/ml, with the second after an enhanced adherence intervention (implemented as per current WHO guidelines) or (ii) a single VL value > 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 VL > 1000 copies/ml to define ART failure would lead to a higher proportion of persons with NNRTI 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 1st line ART with a viral load > 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 1,322 (90% range 67 to 3,513) AIDS deaths averted per year over three 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 VL>1000 copies/ml should be considered. FUNDING: No specific funding was obtained for the analysis or writing of this manuscript.
  • Female Genital Schistosomiasis and HIV: Research Urgently Needed to Improve Understanding of the Health Impacts of This Important Coinfection

    O'Brien, D; Ford, N; Djirmay, AG; Calmy, A; Vitoria, M; Jensen, TO; Christinet, V (Lippincott Williams and Wilkins, 2019-04-15)
    Evidence suggests that there are important interactions between HIV and female genital schistosomiasis (FGS) that may have significant effects on individual and population health. However, the exact way they interact and the health impacts of the interactions are not well understood. In this article, we discuss what is known about the interactions between FGS and HIV, and the potential impact of the interactions. This includes the likelihood that FGS is an important health problem for HIV-positive women in Schistosoma-endemic areas potentially associated with an increased risk of mortality, cancer, and infertility. In addition, it may be significantly impacting the HIV epidemic in sub-Saharan Africa by making young women more susceptible to HIV. We call for immediate action and argue that research is urgently required to address these knowledge gaps and propose a research agenda to achieve this.
  • High incidence of intended partner pregnancy among men living with HIV in rural Uganda: Implications for safer conception services.

    Kaida, A; Kabakyenga, J; Bwana, M; Bajunirwe, F; Mayindike, W; Bennett, K; Kembabazi, A; Haberer, JE; Boum, Y; Martin, JN; et al. (Lippincott Williams and Wilkins, 2019-04-15)
    Many men with HIV express fertility intentions and nearly half have HIV-uninfected sexual partners. We measured partner pregnancy among a cohort of men accessing antiretroviral therapy (ART) in Uganda. Self-reported partner pregnancy incidence and bloodwork (CD4, HIV-RNA) were collected quarterly. Interviewer-administered questionnaires assessed men's sexual and reproductive health annually and repeated at time of reported pregnancy (2011-2015). We measured partner pregnancy incidence overall, by pregnancy intention, and by reported partner HIV-serostatus. We assessed viral suppression (≤400 copies/mL) during the peri-conception period. Cox proportional hazard regression with repeated events identified predictors of partner pregnancy. Among 189 men, baseline median age was 39.9 years [IQR:34.7,47.0], years on ART was 3.9 [IQR:0.0,5.1], and 51% were virally suppressed. Over 530.2 person-years of follow-up, 63 men reported 85 partner pregnancies (incidence=16.0/100 person-years); 45% with HIV-serodifferent partners. By three years of follow-up, 30% of men reported a partner pregnancy, with no difference by partner HIV-serostatus (p=0.75). 69% of pregnancies were intended, 18% wanted but mis-timed, and 8% unwanted. 78% of men were virally suppressed prior to pregnancy report. Men who were younger (aHR:0.94/year;95%CI:0.89-0.99), had incomplete primary education (aHR:2.95;95%CI:1.36-6.40), and reported fertility desires (aHR:2.25;95%CI:1.04-4.85) had higher probability of partner pregnancy. A high incidence of intended partner pregnancy highlights the need to address men's reproductive goals within HIV care. Nearly half of pregnancy partners were at-risk for HIV and one-quarter of men were not virally suppressed during peri-conception. Safer conception care provides opportunity to support men's health and reproductive goals, while preventing HIV transmission to women and infants.
  • Patient and health-care worker experiences of an HIV viral load intervention using SMS: A qualitative study.

    Venables, E; Ndlovu, Z; Munyaradzi, D; Martinez-Perez, G; Mbofana, E; Nyika, P; Chidawanyika, H; Bygrave, H; Garone, D (Public Library of Science, 2019-04-11)
    Mobile Health or mHealth interventions, including Short Message Service (SMS), can help increase access to care, enhance the efficiency of health service delivery and improve diagnosis and treatment for HIV. Text messaging, or SMS, allows for the low cost transmission of information, and has been used to send appointment reminders, information about HIV counselling and treatment, messages to encourage adherence and information on nutrition and side-effects. HIV Viral Load (VL) monitoring is recommended by the WHO and has been progressively adopted in many settings. In Zimbabwe, implementation of VL is routine and has been rolled out with support of Médecins Sans Frontières (MSF) since 2012. An SMS intervention to assist with the management of VL results was introduced in two rural districts of Zimbabwe. After completion of the HIV VL testing at the National Microbiology Reference Laboratory in Harare, results were sent to health facilities via SMS. Consenting patients were also sent an SMS informing them that their viral load results were ready for collection at their nearest health facilities. No actual VL results were sent to patients. A qualitative study was conducted in seven health-care facilities using in-depth interviews (n = 32) and focus group discussions (n = 5) to explore patient and health-care worker experiences of the SMS intervention. Purposive sampling was used to select participants to ensure that male and female patients, as well as those with differing VL results and who lived differing distances from the clinics were included. Data were transcribed, translated from Shona into English, coded and thematically analysed using NVivo software. The VL SMS intervention was considered acceptable to patients and health-care workers despite some challenges in implementation. The intervention was perceived by health-care workers as improving adherence and well-being of patients as well as improving the management of VL results at health facilities. However, there were some concerns from participants about the intervention, including challenges in understanding the purpose and language of the messages and patients coming to their health facility unnecessarily. Health-care workers were more concerned than patients about unintentional HIV disclosure relating to the content of the messages or phone-sharing. This was an innovative intervention in Zimbabwe, in which SMS was used to send VL results to health-care facilities, and notifications of the availability of VL results to patients. Interventions such as this have the potential to reduce unnecessary clinic visits and ensure patients with high VL results receive timely support, but they need to be properly explained, alongside routine counselling, for patients to fully benefit. The findings of this study also have potential policy implications, as if implemented well, such an SMS intervention has the potential to help patients adopt a more active role in the self-management of their HIV disease, become more aware of the importance of adherence and VL monitoring and seek follow-up at clinics when results are high.
  • Lessons learned: Retrospective assessment of outcomes and management of patients with advanced HIV disease in a semi-urban polyclinic in Epworth, Zimbabwe.

    Blankley, S; Gashu, T; Ahmad, B; Belaye, AK; Ringtho, L; Mesic, A; Zizhou, S; Casas, EC (Public Library of Science, 2019-04-10)
    HIV continues to be one of the leading causes of infectious death worldwide and presentation with advanced HIV disease is associated with increased morbidity and mortality. Recommendations for the management of advanced HIV disease include prompt screening and treatment of opportunistic infections, rapid initiation of ART and intensified adherence support. We present treatment outcomes of a cohort of patients presenting with advanced HIV disease in a semi-urban Zimbabwean polyclinic. Retrospective cohort analysis of adult patients enrolled for care at Epworth polyclinic, Zimbabwe between 2007 and end June 2016. Treatment outcomes at 6 and 12 months were recorded. Multivariate logistical regression analysis was undertaken to identify risk factors for presentation with advanced HIV Disease (CD4 count less than 200 cells/mm3 or WHO stage 3 or 4) and risks for attrition at 12 months. 16,007 anti-retroviral therapy naive adult patients were included in the final analysis, 47.4% of whom presented with advanced HIV disease. Patients presenting with advanced HIV disease had a higher mortality rate at 12 months following enrollment compared to early stage patients (5.11% vs 0.45%). Introduction of a package of differentiated care for patients with a CD4 count of less than 100 cells/mm3 resulted in diagnosis of cryptococcal antigenaemia in 7% of patients and a significant increase in the diagnosis of TB, although there was no significant difference in attrition at 6 or 12 months for these patients compared to those enrolled prior to the introduction of the differentiated care. The burden of advanced HIV disease remained high over the study period in this semi-urban polyclinic in Zimbabwe. Introduction of a package of differentiated care for those with advanced HIV disease increased the diagnosis of opportunistic infections and represents a model of care which can be replicated in other polyclinics in the resource constrained Zimbabwean context.
  • Programmatic outcomes and impact of rapid public sector antiretroviral therapy expansion in adults prior to introduction of the WHO treat-all approach in rural Eswatini.

    Boulle, A; Teck, R; Lukhele, N; Rusch, B; Telnov, A; Mabhena, E; Pasipamire, L; Ciglenecki, I; Schomaker, M; Kerschberger, B (John Wiley & Sons, 2019-04-01)
    To assess long-term antiretroviral therapy (ART) outcomes during rapid HIV programme expansion in the public sector of Eswatini (formerly Swaziland). This is a retrospectively established cohort of HIV-positive adults (≥16 years) who started first-line ART in 25 health facilities in Shiselweni (Eswatini) between 01/2006 and 12/2014. Temporal trends in ART attrition, treatment expansion and ART coverage were described over 9 years. We used flexible parametric survival models to assess the relationship between time to ART attrition and covariates. Of 24 772 ART initiations, 6% (n = 1488) occurred in 2006, vs. 13% (n = 3192) in 2014. Between these years, median CD4 cell count at ART initiation increased (113-265 cells/mm Programmatic outcomes improved during large expansion of the treatment cohort and increased ART coverage. Changes in ART programming may have contributed to better outcomes.

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