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  • Slipping through the cracks: a qualitative study to explore pathways of HIV care and treatment amongst hospitalised patients with advanced HIV in Kenya and the Democratic Republic of the Congo.

    Burns, R; Venables, E; Odhoch, L; Kocholla, L; Wanjala, S; Mucinya, G; Bossard, C; Wringe, A (Taylor and Francis, 2021-08-26)
    Advanced HIV causes substantial mortality in sub-Saharan Africa despite widespread antiretroviral therapy coverage. This paper explores pathways of care amongst hospitalised patients with advanced HIV in rural Kenya and urban Democratic Republic of the Congo, with a view to understanding their care-seeking trajectories and poor health outcomes. Thirty in-depth interviews were conducted with hospitalised patients with advanced HIV who had previously initiated first-line antiretroviral therapy, covering their experiences of living with HIV and care-seeking. Interviews were audio-recorded, transcribed and translated before being coded inductively and analysed thematically. In both settings, participants' health journeys were defined by recurrent, severe symptoms and complex pathways of care before hospitalisation. Patients were often hospitalised after multiple failed attempts to obtain adequate care at health centres. Most participants managed their ill-health with limited support networks, lived in fragile economic situations and often experienced stress and other mental health concerns. Treatment-taking was sometimes undermined by strict messaging around adherence that was delivered in health facilities. These findings reveal a group of patients who had "slipped through the cracks" of health systems and social support structures, indicating both missed opportunities for timely management of advanced HIV and the need for interventions beyond hospital and clinical settings.
  • Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen.

    Keene, CM; Griesel, R; Zhao, Y; Gewabe, Z; Sayed, K; Hill, A; Cassidy, T; Ngwenya, O; Jackson, A; van Zyl, G; et al. (Gower Academic Journals, 2021-07-15)
    Objective: Recycling tenofovir and lamivudine/emtricitabine (XTC) with dolutegravir would provide a more tolerable, affordable, and scalable second-line regimen than dolutegravir with an optimized nucleoside reverse transcriptase inhibitor (NRTI) backbone. We evaluated efficacy of tenofovir/lamivudine/dolutegravir (TLD) in patients failing first-line tenofovir/XTC/efavirenz or nevirapine. Design: Single arm, prospective, interventional study. Setting: Two primary care clinics in Khayelitsha, South Africa. Participants: Sixty adult patients with two viral loads greater than 1000 copies/ml. Intervention: Participants were switched to TLD with additional dolutegravir (50 mg) for 2 weeks to overcome efavirenz induction. Primary outcome: Proportion achieving viral load less than 50 copies/ml at week 24 using the FDA snapshot algorithm. Results: Baseline median CD4+ cell count was 248 cells/μl, viral load 10 580 copies/ml and 48 of 54 (89%) had resistance (Stanford score ≥15) to one or both of tenofovir and XTC. No participants were lost to follow-up. At week 24, 51 of 60 [85%, 95% confidence interval (CI) 73-93%] were virologically suppressed, six had viral load 50-100 copies/ml, one had viral load 100-1000 copies/ml, one no viral load in window, and one switched because of tenofovir-related adverse event. No integrase mutations were detected in the one participant meeting criteria for resistance testing. Virological suppression was achieved by 29 of 35 (83%, 95% CI 66-93%) with resistance to tenofovir and XTC, 11 of 13 (85%, 95% CI 55-98%) with resistance to XTC, and six of six (100%, 95% CI 54-100%) with resistance to neither. Conclusion: A high proportion of adults switching to second-line TLD achieved virologic suppression despite substantial baseline NRTI resistance and most not suppressed had low-level viraemia (≤100 copies/ml). This suggests recycling tenofovir and XTC with dolutegravir could provide an effective second-line option.
  • High Prevalence of NRTI and NNRTI Drug Resistance Among ART-Experienced, Hospitalized Inpatients.

    Bossard, C; Schramm, B; Wanjala, S; Jain, L; Mucinya, G; Opollo, V; Wiesner, L; van Cutsem, G; Poulet, E; Szumilin, E; et al. (Lippincott Williams & Wilkins, 2021-07-01)
    Background: Patients hospitalized with advanced HIV have a high mortality risk. We assessed viremia and drug resistance among differentiated care services and explored whether expediting the switching of failing treatments may be justified. Setting: Hospitals in the Democratic Republic of (DRC) Congo (HIV hospital) and Kenya (general hospital including HIV care). Methods: Viral load (VL) testing and drug resistance (DR) genotyping were conducted for HIV inpatients ≥15 years, on first-line antiretroviral therapy (ART) for ≥6 months, and CD4 ≤350 cells/µL. Dual-class DR was defined as low-, intermediate-, or high-level DR to at least 1 nucleoside reverse transcriptase inhibitor and 1 non-nucleoside reverse transcriptase inhibitor. ART regimens were considered ineffective if dual-class DR was detected at viral failure (VL ≥1000 copies/mL). Results: Among 305 inpatients, 36.7% (Kenya) and 71.2% (DRC) had VL ≥1000 copies/mL, of which 72.9% and 73.7% had dual-class DR. Among viral failures on tenofovir disoproxil fumarate (TDF)-based regimens, 56.1% had TDF-DR and 29.8% zidovudine (AZT)-DR; on AZT regimens, 71.4% had AZT-DR and 61.9% TDF-DR, respectively. Treatment interruptions (≥48 hours during past 6 months) were reported by 41.7% (Kenya) and 56.7% (DRC). Approximately 56.2% (Kenya) and 47.4% (DRC) on TDF regimens had tenofovir diphosphate concentrations <1250 fmol/punch (suboptimal adherence). Among viral failures with CD4 <100 cells/µL, 76.0% (Kenya) and 84.6% (DRC) were on ineffective regimens. Conclusions: Many hospitalized, ART-experienced patients with advanced HIV were on an ineffective first-line regimen. Addressing ART failure promptly should be integrated into advanced disease care packages for this group. Switching to effective second-line medications should be considered after a single high VL on non-nucleoside reverse transcriptase inhibitor-based first-line if CD4 ≤350 cells/µL or, when VL is unavailable, among patients with CD4 ≤100 cells/µL.
  • Treated HIV Infection and Progression of Carotid Atherosclerosis in Rural Uganda: A Prospective Observational Cohort Study.

    Siedner, MJ; Bibangambah, P; Kim, JH; Lankowski, A; Chang, JL; Yang, IT; Kwon, DS; North, CM; Triant, VA; Longenecker, C; et al. (Wiley-Blackwell, 2021-06-05)
    Background Although ≈70% of the world's population of people living with HIV reside in sub-Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region. Methods and Results We conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population-based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3-4, range 1-5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, P=0.15). In multivariable models, increasing age, blood pressure, and non-high-density lipoprotein cholesterol were associated with greater cIMT (P<0.05), however change in cIMT per year was also no different by HIV serostatus (0.004 mm/year for HIV negative [95% CI, 0.001-0.007 mm], 0.006 mm/year for people living with HIV [95% CI, 0.003-0.008 mm], HIV×time interaction P=0.25). Conclusions In rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub-Saharan Africa. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02445079.
  • What gaps remain in the HIV cascade of care? Results of a population-based survey in Nsanje District, Malawi.

    Conan, N; Paye, CP; Ortuno, R; Chijuwa, A; Chiwandira, B; Goemaere, E; Garone, DB; Coulborn, RM; Chihana, M; Maman, D (Public Library of Science, 2021-04-22)
    Introduction: The Malawi Ministry of Health (MoH) has been in collaboration with Médecins sans Frontières (MSF) to increase access to quality HIV care through decentralization of antiretroviral therapy (ART) diagnosis and treatment from hospital to clinics in Nsanje District since 2011. A population-based household survey was implemented to provide information on HIV prevalence and cascade of care to inform and prioritize community-based HIV interventions in the district. Methods: A cross-sectional survey was conducted between September 2016 and January 2017. Using two-stage cluster sampling, eligible adult individuals aged ≥15 years living in the selected households were asked to participate. Participants were interviewed and tested for HIV at home. Those tested HIV-positive had their HIV-RNA viral load (VL) measured, regardless of their ART status. All participants tested HIV-positive at the time of the survey were advised to report their HIV test result to the health facility of their choice that MSF was supported in the district. HIV-RNA VL results were made available in this health facility. Results: Among 5,315 eligible individuals, 91.1% were included in the survey and accepted an HIV test. The overall prevalence was 12.1% (95% Confidence Interval (CI): 11.2-13.0) and was higher in women than in men: 14.0% versus 9.5%, P<0.001. Overall HIV-positive status awareness was 80.0% (95%CI: 76.4-83.1) and was associated with sex (P<0.05). Linkage to care was 78.0% (95%CI: 74.3-81.2) and participants in care 76.2% (95%CI: 72.4-79.5). ART coverage among participants aware of their HIV-positive status was 95.3% (95%CI: 92.9-96.9) and was not associated with sex (P = 0.55). Viral load suppression among participants on ART was 89.9% (95%CI: 86.6-92.4) and was not statistically different by sex (p = 0.40). Conclusions: Despite encouraging results in HIV testing coverage, cascade of care, and UNAIDS targets in Nsanje District, some gap remains in the first 90, specifically among men and young adults. Enhanced community engagement and new strategies of testing, such as index testing, could be implemented to identify those who are still undiagnosed, particularly men and young adults.
  • Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis.

    Mesic, A; Spina, A; Mar, HT; Thit, P; Decroo, T; Lenglet, A; Thandar, MP; Thwe, TT; Kyaw, AA; Homan, T; et al. (BioMed Central, 2021-04-21)
    Background: Progress toward the global target for 95% virological suppression among those on antiretroviral treatment (ART) is still suboptimal. We describe the viral load (VL) cascade, the incidence of virological failure and associated risk factors among people living with HIV receiving first-line ART in an HIV cohort in Myanmar treated by the Médecins Sans Frontières in collaboration with the Ministry of Health and Sports Myanmar. Methods: We conducted a retrospective cohort study, including adult patients with at least one HIV viral load test result and having received of at least 6 months' standard first-line ART. The incidence rate of virological failure (HIV viral load ≥ 1000 copies/mL) was calculated. Multivariable Cox's regression was performed to identify risk factors for virological failure. Results: We included 25,260 patients with a median age of 33.1 years (interquartile range, IQR 28.0-39.1) and a median observation time of 5.4 years (IQR 3.7-7.9). Virological failure was documented in 3,579 (14.2%) participants, resulting in an overall incidence rate for failure of 2.5 per 100 person-years of follow-up. Among those who had a follow-up viral load result, 1,258 (57.1%) had confirmed virological failure, of which 836 (66.5%) were switched to second-line treatment. An increased hazard for failure was associated with age ≤ 19 years (adjusted hazard ratio, aHR 1.51; 95% confidence intervals, CI 1.20-1.89; p < 0.001), baseline tuberculosis (aHR 1.39; 95% CI 1.14-1.49; p < 0.001), a history of low-level viremia (aHR 1.60; 95% CI 1.42-1.81; p < 0.001), or a history of loss-to-follow-up (aHR 1.24; 95% CI 1.41-1.52; p = 0.041) and being on the same regimen (aHR 1.37; 95% CI 1.07-1.76; p < 0.001). Cumulative appointment delay was not significantly associated with failure after controlling for covariates. Conclusions: VL monitoring is an important tool to improve programme outcomes, however limited coverage of VL testing and acting on test results hampers its full potential. In our cohort children and adolescents, PLHIV with history of loss-to-follow-up or those with low-viremia are at the highest risk of virological failure and might require more frequent virological monitoring than is currently recommended.
  • PrEP reminds me that I am the one to take responsibility of my life: a qualitative study exploring experiences of and attitudes towards pre-exposure prophylaxis use by women in Eswatini.

    Bjertrup, PJ; Mmema, N; Dlamini, V; Ciglenecki, I; Mpala, Q; Matse, S; Kerschberger, B; Wringe, A (BioMed Central, 2021-04-14)
    Background: Pre-exposure-prophylaxis (PrEP) has been heralded for its potential to put women in control of preventing HIV infection, but uptake and continuation rates have been disappointing in high-incidence settings in sub-Saharan Africa. We explored structural and social factors that influenced PrEP use among young women and pregnant or breastfeeding women in rural Eswatini. Methods: We conducted two in-depth interviews with ten women on PrEP, and one-time in-depth interviews with fourteen women who declined or discontinued PrEP. Interviews covered decision-making processes around PrEP initiation and experiences with pill-taking. In-depth interviews were conducted with nine health workers, covering experiences in delivering PrEP services, and two focus group discussions were held with men to elicit their perceptions of PrEP. Interviews and discussions were audio-recorded, translated, transcribed and analysed thematically, using an inductive approach. Results: PrEP initiation and use were experienced by many women as empowering them to take control of their health and well-being, and stay HIV free, facilitating them to realise their aspirations relating to motherhood and educational attainment. However, the social norms that defined relationship dynamics with partners or family members either undermined or promoted this empowerment potential. In particular, young women were rarely supported by family members to take PrEP unless it was perceived to be for protecting an unborn child. Stigmatisation of pill-taking through its associations with HIV and the burden of daily pill-taking also contributed to PrEP discontinuation. Conclusions: Unlike many prevention tools, PrEP enabled women to achieve a sense of control over their lives. Nevertheless, women's agency to continue and adhere to PrEP was influenced by social and structural factors including gender norms, family expectations of young women, relationship dynamics and stigma related to HIV. Future interventions should address these barriers to promote PrEP use among sexually-active women.
  • The Impact of Same-Day Antiretroviral Therapy Initiation under the WHO Treat-All Policy.

    Kerschberger, B; Boulle, A; Kuwengwa, R; Ciglenecki, I; Schomaker, M (Oxford University Press, 2021-02-12)
    Rapid initiation of antiretroviral therapy (ART) is recommended for people living with HIV, with the option to start treatment on the day of diagnosis (same-day-ART). However, the effect of same-day-ART remains unknown in realistic public sector settings. We established a cohort of ≥16-year-old patients who initiated first-line ART under Treat-All in Nhlangano (Eswatini) between 2014-2016, either on the day of HIV care enrolment (same-day-ART) or 1–14 days thereafter (early-ART). Directed acyclic graphs, flexible parametric survival analysis and targeted maximum likelihood estimation (TMLE) were used to estimate the effect of same-day-ART initiation on the composite unfavourable treatment outcome (loss to follow-up;death;viral failure). Of 1328 patients, 839 (63.2%) initiated same-day ART. The adjusted hazard ratio of the unfavourable outcome was increased by 1.48 (95% CI:1.16–1.89) for same-day-ART compared with early-ART. TMLE suggested that after 1 year, 28.9% of patients would experience the unfavourable outcome under same-day-ART compared with 21.2% under early-ART (difference: 7.7%; 1.3–14.1%). This estimate was driven by loss to follow-up and varied over time, with a higher hazard during the first year after HIV care enrolment and a similar hazard thereafter. We found an increased risk with same-day-ART. A limitation was possible silent transfers that were not captured.
  • "It's a secret between us": a qualitative study on children and care-giver experiences of HIV disclosure in Kinshasa, Democratic Republic of Congo.

    Sumbi, EM; Venables, E; Harrison, R; Garcia, M; Iakovidi, K; van Cutsem, G; Chalachala, JL (BMC, 2021-02-06)
    Background: It is estimated that 64,000 children under 15 years of age are living with HIV in the Democratic Republic of Congo (DRC). Non-disclosure - in which the child is not informed about their HIV status - is likely to be associated with poor outcomes during adolescence including increased risk of poor adherence and retention, and treatment failure. Disclosing a child's HIV status to them can be a difficult process for care-givers and children, and in this qualitative study we explored child and care-giver experiences of the process of disclosing, including reasons for delay. Methods: A total of 22 in-depth interviews with care-givers and 11 in-depth interviews with HIV positive children whom they were caring for were conducted in one health-care facility in the capital city of Kinshasa. Care-givers were purposively sampled to include those who had disclosed to their children and those who had not. Care-givers included biological parents, grandmothers, siblings and community members and 86% of them were female. Interviews were conducted in French and Lingala. All interviews were translated and/or transcribed into French before being manually coded. Thematic analysis was conducted. Verbal informed consent/assent was taken from all interviewees. Results: At the time of interview, the mean age of children and care-givers was 17 (15-19) and 47 (21-70) years old, respectively. Many care-givers had lost family members due to HIV and several were HIV positive themselves. Reasons for non-disclosure included fear of stigmatisation; wanting to protect the child and not having enough knowledge about HIV or the status of the child to disclose. Several children had multiple care-givers, which also delayed disclosure, as responsibility for the child was shared. In addition, some care-givers were struggling to accept their own HIV status and did not want their child to blame them for their own positive status by disclosing to them. Conclusions: Child disclosure is a complex process for care-givers, health-care workers and the children themselves. Care-givers may require additional psycho-social support to manage disclosure. Involving multiple care-givers in the care of HIV positive children could offer additional support for disclosure.
  • Virologic response of adolescents living with perinatally acquired HIV receiving antiretroviral therapy in the period of early adolescence (10-14 years) in South Africa.

    Nyakato, P; Schomaker, M; Sipambo, N; Technau, KG; Fatti, G; Rabie, H; Tanser, F; Eley, B; Euvrard, J; Wood, R; et al. (Lippincott, Williams & Wilkins, 2021-01-21)
    Background and objectives: Adolescents living with perinatally acquired HIV (ALPHIV) on antiretroviral therapy (ART) have been noted to have poorer adherence, retention and virologic control compared to adolescents with nonperinatally acquired HIV, children or adults. We aimed to describe and examine factors associated with longitudinal virologic response during early adolescence. Design: A retrospective cohort study Methods: We included ALPHIV who initiated ART before age 9.5 years in South African cohorts of the International epidemiology Database to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration (2004–2016); with viral load (VL) values <400 copies/ml at age 10 years and at least one VL measurement after age 10 years. We used a log-linear quantile mixed model to assess factors associated with elevated (75th quantile) VLs. Results: We included 4396 ALPHIV, 50.7% were male, with median (interquartile range) age at ART start of 6.5 (4.5, 8.1) years. Of these, 74.9% were on a nonnucleoside reverse transcriptase inhibitor (NNRTI) at age 10 years. After adjusting for other patient characteristics, the 75th quantile VLs increased with increasing age being 3.13-fold (95% CI 2.66, 3.68) higher at age 14 versus age 10, were 3.25-fold (95% CI 2.81, 3.75) higher for patients on second-line protease-inhibitor and 1.81-fold for second-line NNRTI-based regimens (versus first-line NNRTI-based regimens). There was no difference by sex. Conclusions: As adolescents age between 10 and 14 years, they are increasingly likely to experience higher VL values, particularly if receiving second-line protease inhibitor or NNRTI-based regimens, which warrant adherence support interventions.
  • Prevalence of HIV, viral hepatitis B/C and tuberculosis and treatment outcomes among people who use drugs: Results from the implementation of the first drop-in-center in Mozambique

    Sema Baltazar, C; Kellogg, TA; Boothe, M; Loarec, A; de Abreu, E; Condula, M; Fazito, E; Raymond, HF; Temmerman, M; Luchters, S (Elsevier, 2021-01-08)
    Background People who use drugs (PWUD) which includes both people who inject drugs (PWID) and non-injection drug users (NIDU) are marginalized, experience high levels of stigma and discrimination, and are likely to have challenges with accessing health services. Mozambique implemented the first drop-in center (DIC) for PWUD in Maputo City in 2018. This analysis aims to assess the prevalence of HIV, viral hepatitis B (HBV) and C (HCV) and tuberculosis (TB) among PWUD, and assess their linkage to care and associated correlates. Methods We conducted a cross-sectional retrospective analysis of routine screening data collected from the first visit at the drop-in center (DIC) during the period of May 2018 to November 2019 (18 months). Descriptive and multivariable logistic regression analysis were conducted to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) of HIV, HBV, HCV and TB infections among PWID and NIDU. Cox proportional hazards models of determinants were used to estimate time from HIV diagnosis to linkage to care for PWUD. Results A total of 1,818 PWUD were screened at the DIC, of whom 92.6% were male. The median age was 27 years (range:14–63). Heroin was the most consumed drug (93.8%), and among people who used it, 15.5% injected it. Prevalence of HIV (43.9%), HCV (22.6%) and HBV (5.9%) was higher among PWID (p<0.001). Linkage to HIV care was observed in 40.5% of newly diagnosed PWID. Factors associated with shorter time to linkage to care included drug injection (aHR=1.6) and confirmed TB infection (aHR=2.9). Conclusion This was the first analysis conducted on the implementation of the DIC in Mozambique and highlights the importance of targeted services for this high-risk population. Our analysis confirmed a high prevalence of HIV, HBV and HCV, and highlight the challenges with linkage to care among PWID. The expansion of DIC locations to other high-risk localities to enhance HIV testing, treatment services and linkage to care to reduce ongoing transmission of HIV, HBV, HCV and TB and improve health outcomes.
  • Outcomes of AIDS-associated Kaposi sarcoma in Mozambique after treatment with pegylated liposomal doxorubicin

    Coldiron, ME; Gutierrez Zamudio, AG; Manuel, R; Luciano, G; Rusch, B; Ciglenecki, I; Telnov, A; Grais, RF; Trellu, LT; Molfino, L (BMC, 2021-01-07)
    Background Kaposi’s sarcoma (KS) is a common HIV-associated malignancy frequently associated with poor outcomes. It is the most frequently diagnosed cancer in major cities of Mozambique. Antiretroviral therapy is the cornerstone of KS treatment, but many patients require cytotoxic chemotherapy. The traditional regimen in Mozambique includes conventional doxorubicin, bleomycin and vincristine, which is poorly tolerated. In 2016, pegylated liposomal doxorubicin was introduced at a specialized outpatient center in Maputo, Mozambique. Methods We performed a prospective, single-arm, open-label observational study to demonstrate the feasibility, safety, and outcomes of treatment with pegylated liposomal doxorubicin (PLD) in patients with AIDS-associated Kaposi sarcoma (KS) in a low-resource setting. Chemotherapy-naïve adults with AIDS-associated KS (T1 or T0 not responding to 6 months of antiretroviral therapy) were eligible if they were willing to follow up for 2 years. Patients with Karnofsky scores < 50 or contraindications to PLD were excluded. One hundred eighty-three patients were screened and 116 participants were enrolled. Patients received PLD on three-week cycles until meeting clinical stopping criteria. Follow-up visits monitored HIV status, KS disease, side effects of chemotherapy, mental health (PHQ-9) and quality of life (SF-12). Primary outcome measures included vital status and disease status at 6, 12, and 24 months after enrollment. Results At 24 months, 23 participants (20%) had died and 15 (13%) were lost to follow-up. Baseline CD4 < 100 was associated with death (HR 2.7, 95%CI [1.2–6.2], p = 0.016), as was T1S1 disease compared to T1S0 disease (HR 2.7, 95%CI [1.1–6.4], p = 0.023). Ninety-two participants achieved complete or partial remission at any point (overall response rate 80%), including 15 (13%) who achieved complete remission. PLD was well-tolerated, and the most common AEs were neutropenia and anemia. Quality of life improved rapidly after beginning PLD. Discussion PLD was safe, well-tolerated and effective as first-line treatment of KS in Mozambique. High mortality was likely due to advanced immunosuppression at presentation, underscoring the importance of earlier screening and referral for KS.
  • Ending deaths from HIV-related cryptococcal meningitis by 2030

    Shroufi, A; Chiller, T; Jordan, A; Denning, DW; Harrison, TS; Govender, NP; Loyse, A; Baptiste, S; Rajasingham, R; Boulware, DR; et al. (Elsevier, 2021-01-01)
    The UNAIDS target to reduce HIV-related death to fewer than 500 000 deaths per year by 2020 will not be met. 1 This statement might not be headline grabbing as this target was never as prominent as the 90-90-90 targets, 2 the achievement of which is a necessary but not sufficient step towards ending AIDS mortality.
  • Urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in the medical wards identifies a large proportion of patients with tuberculosis at risk of death

    Huerga, H; Mathabire Rucker, SC; Bastard, M; Mpunga, J; Amoros Quiles, I; Kabaghe, C; Sannino, L; Szumilin, E (Oxford University Press, 2020-12-23)
    Background Diagnosing tuberculosis (TB), the leading cause of death in people with HIV, remains a challenge in resource-limited countries. We assessed TB diagnosis using a strategy that included systematic urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in the medical wards and 6-month mortality according to the LAM result. Methods This prospective, observational study included adult HIV patients hospitalized in the medical wards of a public district hospital in Malawi regardless of their TB symptoms or CD4 count. Each patient had a clinical examination and Alere Determine TB-LAM, sputum microscopy, sputum GeneXpert MTB/RIF (Xpert), chest X-ray, and CD4 count were systematically requested. Results Among 387 inpatients, 54% had a CD4<200 cells/µL, 64% had presumptive TB and 90% had ≥1 TB symptom recorded in the medical file. LAM results were available for 99.0% of the patients, microscopy for 62.8% and Xpert for 60.7%. In total, 26.1% (100/383) had LAM-positive results, 48% (48/100) of which were grades 2-4. Any TB laboratory test result was positive in 30.8% (119/387). Among patients with no Xpert result, 28.5% (43/151) were LAM-positive. Cumulative 6-months mortality was 40.1% (151/377): 50.5% (49/97) in LAM-positives and 36.2% (100/276) in LAM-negatives, p=0.013. In multivariable regression analyses, LAM-positive patients had higher risk of mortality than LAM-negatives (aOR: 2.5, 95%CI: 1.1-5.8, p=0.037). Conclusions In resource-limited hospital medical wards with high TB prevalence, a diagnostic strategy including systematic urine-LAM testing for all HIV patients is an easily implementable strategy that identifies a large proportion of patients with TB at risk of death.
  • Urine Lipoarabinomannan Testing for All HIV Patients Hospitalized in Medical Wards Identifies a Large Proportion of Patients With Tuberculosis at Risk of Death.

    Huerga, H; Rucker, SCM; Bastard, M; Mpunga, J; Amoros Quiles, I; Kabaghe, C; Sannino, L; Scumilin, E (Oxford University Press, 2020-12-23)
    Among 387 inpatients, 54% had a CD4 <200 cells/µL, 64% had presumptive TB, and 90% had ≥1 TB symptom recorded in their medical file. LAM results were available for 99.0% of patients, microscopy for 62.8%, and Xpert for 60.7%. In total, 26.1% (100/383) had LAM-positive results, 48% (48/100) of which were grades 2-4. Any TB laboratory test result was positive in 30.8% (119/387). Among patients with no Xpert result, 28.5% (43/151) were LAM-positive. Cumulative 6-month mortality was 40.1% (151/377): 50.5% (49/97) in LAM-positives and 36.2% (100/276) in LAM-negatives (P = .013). In multivariable regression analyses, LAM-positive patients had a higher risk of mortality than LAM-negatives (adjusted odds ratio, 2.5; 95% CI, 1.1-5.8; P = .037).
  • Twenty‐four‐month outcomes from a cluster‐randomized controlled trial of extending antiretroviral therapy refills in ART adherence clubs

    Cassidy, T; Grimsrud, A; Keene, C; Lebelo, K; Hayes, H; Orrell, C; Zokufa, N; Mutsetekwa, T; Voget, J; Gerstenhaber, R; et al. (Wiley Open Access, 2020-12-19)
    Introduction The antiretroviral therapy (ART) adherence club (AC) model has supported clinically stable HIV patients’ retention with group ART refills and psychosocial support. Reducing visit frequency by increasing ART refills to six months could further benefit patients and unburden health systems. We conducted a pragmatic non‐inferiority cluster randomized trial comparing standard of care (SoC) ACs and six‐month refill intervention ACs in a primary care facility in Khayelitsha, South Africa. Methods Existing community‐based and facility‐based ACs were randomized to either SoC or intervention ACs. SoC ACs met five times annually, receiving two‐month refills with a four‐month refill over year‐end. Blood was drawn at one AC visit with a clinical assessment at the next. Intervention ACs met twice annually receiving six‐month refills, with an individual blood collection visit before the annual clinical assessment AC visit. The first study visits were in October and November 2017 and participants followed for 27 months. We report retention in care, viral load completion and viral suppression (<400 copies/mL) 24 months after enrolment and calculated intention‐to‐treat risk differences for the primary outcomes using generalized estimating equations specifying for clustering by AC. Results Of 2150 participants included in the trial, 977 were assigned to the intervention arm (40 ACs) and 1173 to the SoC (48 ACs). Patient characteristics at enrolment were similar across groups. Retention in care at 24 months was similarly high in both arms: 93.6% (1098/1173) in SoC and 92.6% (905/977) in the intervention arm, with a risk difference of −1.0% (95% CI: −3.2 to 1.3). The intervention arm had higher viral load completion (90.8% (999/1173) versus 85.1% (887/977)) and suppression (87.3% (969 /1173) versus 82.6% (853/977)) at 24 months, with a risk difference for completion of 5.5% (95% CI: 1.5 to 9.5) and suppression of 4.6% (95% CI: 0.2 to 9.0). Conclusions Intervention AC patients receiving six‐month ART refills showed non‐inferior retention in care, viral load completion and viral load suppression to those in SoC ACs, adding to a growing literature showing good outcomes with extended ART dispensing intervals.
  • Factors associated with antiretroviral treatment failure among people living with HIV on antiretroviral therapy in resource-poor settings: a systematic review and metaanalysis

    Lailulo, Y; Kitenge, M; Jaffer, S; Aluko, O; Nyasulu, PS (BMC, 2020-12-12)
    Background Despite the increase in the number of people accessing antiretroviral therapy (ART), there is limited data regarding treatment failure and its related factors among HIV-positive individuals enrolled in HIV care in resource-poor settings. This review aimed to identify factors associated with antiretroviral treatment failure among individuals living with HIV on ART in resource-poor settings. Methods We conducted a comprehensive search on MEDLINE (PubMed), Excerpta Medica Database (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization’s (WHO’s) library database, and Latin American and Caribbean Health Sciences Literature (LILACS). We included observational studies (cohort, case-control, and cross-sectional studies) where adolescents and adults living with HIV were on antiretroviral treatment regardless of the ART regimen. The primary outcomes of interest were immunological, virological, and clinical failure. Some of the secondary outcomes were mm3 opportunistic infections, WHO clinical stage, and socio-demographic factors. We screened titles, abstracts, and the full texts of relevant articles in duplicate. Disagreements were resolved by consensus. We analyzed the data by doing a meta-analysis to pool the results for each outcome of interest. Results Antiretroviral failure was nearly 6 times higher among patients who had poor adherence to treatment as compared to patients with a good treatment adherence (OR = 5.90, 95% CI 3.50, 9.94, moderate strength of evidence). The likelihood of the treatment failure was almost 5 times higher among patients with CD4 < 200 cells/mm3 compared to those with CD4 ≥ 200 CD4 cells/mm3 (OR = 4.82, 95% CI 2.44, 9.52, low strength of evidence). This result shows that poor adherence and CD4 count below < 200 cells/mm3 are significantly associated with treatment failure among HIV-positive patients on ART in a resource-limited setting. Conclusion This review highlights that low CD4 counts and poor adherence to ART were associated to ART treatment failure. There is a need for healthcare workers and HIV program implementers to focus on patients who have these characteristics in order to prevent ART treatment failure.
  • Radical Pleasure: Feminist Digital Storytelling by, with, and for Women Living with HIV

    Carter, A; Anam, F; Sanchez, M; Roche, J; Wynne, ST; Stash, J; Webster, K; Nicholson, V; Patterson, S; Kaida, A (Springer, 2020-11-24)
    Despite the fact that HIV can be controlled with medication to undetectable levels where it cannot be passed on, stigmatization of women living with HIV persists. Such stigmatization pivots on stereotypes around sex and sexism and has force in women’s lives. Our aim was to create an inspirational resource for women living with HIV regarding sex, relationships, and sexuality: www.lifeandlovewithhiv.ca (launched in July 2018). This paper describes the development and mixed-method evaluation of our first year and a half activities. We situated our work within a participatory arts-based knowledge translation planning framework and used multiple data sources (Google Analytics, stories and comments on the website, team reflections over multiple meetings) to report on interim outcomes and impacts. In our first 1.5 years, we recruited and mentored 12 women living with HIV from around the world (Canada, Australia, New Zealand, Kenya, South Africa, Spain, Nigeria, and the U.S.) to write their own stories, with the support of a mentor/editor, as a way of regaining control of HIV narratives and asserting their right to have pleasurable, fulfilling, and safer sexual lives. Writers published 43 stories about pleasure, orgasm, bodies, identities, trauma, resilience, dating, disclosure, self-love, and motherhood. Our social media community grew to 1600, and our website received approximately 300 visits per month, most by women (70%) and people aged 25–44 years (65%), from more than 50 cities globally, with shifts in use and demographics over time. Qualitative data indicated the power of feminist digital storytelling for opportunity, access, validation, and healing, though not without risks. We offer recommendations to others interested in using arts-based digital methods to advance social equity in sexual health.
  • Treating HIV-associated cytomegalovirus retinitis with oral valganciclovir and intra-ocular ganciclovir by primary HIV clinicians in southern Myanmar: a retrospective analysis of routinely collected data

    Murray, J; Hilbig, A; Soe, TT; Ei, WLSS; Soe, KP; Ciglenecki, I (BMC, 2020-11-13)
    Background Cytomegalovirus retinitis (CMVR) is an opportunistic infection in HIV-infected people. Intraocular or intravenous ganciclovir was gold standard for treatment; however, oral valganciclovir replaced this in high-income countries. Low- and middle-income countries (LMIC) frequently use intraocular injection of ganciclovir (IOG) alone because of cost. Methods Retrospective review of all HIV-positive patients with CMVR from February 2013 to April 2017 at a Médecins Sans Frontièrs HIV clinic in Myanmar. Treatment was classified as local (IOG) or systemic (valganciclovir, or valganciclovir and IOG). The primary outcome was change in visual acuity (VA) post-treatment. Mortality was a secondary outcome. Results Fifty-three patients were included. Baseline VA was available for 103 (97%) patient eyes. Active CMVR was present in 72 (68%) eyes. Post-treatment, seven (13%) patients had improvement in VA, 30 (57%) had no change, and three (6%) deteriorated. Among patients receiving systemic therapy, four (12.5%) died, compared with five (24%) receiving local therapy (p = 0.19). Conclusions Our results from the first introduction of valganciclovir for CMVR in LMIC show encouraging effectiveness and safety in patients with advanced HIV. We urge HIV programmes to include valganciclovir as an essential medicine, and to include CMVR screening and treatment in the package of advanced HIV care.
  • Implementation and operational feasibility of SAMBA I HIV‐1 semi‐quantitative viral load testing at the point‐of‐care in rural settings in Malawi and Uganda

    Gueguen, M; Nicholas, S; Poulet, E; Schramm, B; Szumilin, E; Wolters, L; Wapling, J; Ajule, E; Rakesh, A; Mwenda, R; et al. (Wiley, 2020-11-07)
    Objective We monitored a large‐scale implementation of the Simple Amplification‐Based Assay semi‐quantitative viral load test for HIV‐1 version I (SAMBA I Viral Load = SAMBA I VL) within Médecins Sans Frontières’ HIV programmes in Malawi and Uganda, to assess its performance and operational feasibility. Methods Descriptive analysis of routine programme data between August 2013 and December 2016. The dataset included samples collected for VL monitoring and tested using SAMBA I VL in five HIV clinics in Malawi (four peripheral health centres and one district hospital), and one HIV clinic in a regional referral hospital in Uganda. SAMBA I VL was used for VL testing in patients who had been receiving ART for between 6 months and ten years, to determine whether plasma VL was above or below 1000 copies/mL of HIV‐1, reflecting ART failure or efficacy. Randomly selected samples were quantified with commercial VL assays. SAMBA I instruments and test performance, site throughput, and delays in communicating results to clinicians and patients were monitored. Results Between August 2013 and December 2016 a total of 60 889 patient samples were analysed with SAMBA I VL. Overall, 0.23% of initial SAMBA I VL results were invalid; this was reduced to 0.04% after repeating the test once. Global test failure, including instrument failure, was 1.34%. Concordance with reference quantitative testing of VL was 2620/2727, 96.0% (1338/1382, 96.8% in Malawi; 1282/1345, 95.3% in Uganda). For Chiradzulu peripheral health centres and Arua Hospital HIV clinic, where testing was performed on‐site, same‐day results were communicated to clinicians for between 91% and 97% of samples. Same‐day clinical review was obtained for 84.7% across the whole set of samples tested. Conclusions SAMBA I VL testing is feasible for monitoring cohorts of 1000 to 5000 ART‐experienced patients. Same‐day results can be used to inform rapid clinical decision‐making at rural and remote health facilities, potentially reducing time available for development of resistance and conceivably helping to reduce morbidity and mortality.

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