Risk factors for baseline bedaquiline (BDQ) resistance, amplification during treatment, and correlations with treatment outcomes are not fully understood. This cohort included Armenian patients with multidrug-resistant TB predominantly fluoroquinolone-resistant enrolled between 2013 and 2015 in a BDQ compassionate use program. BDQ resistance at baseline and during treatment was assessed using MGIT (pDSTMGIT), minimal inhibitory concentration in 7H11 (MIC7H11), and whole-genome sequencing. Risk factors, such as treatment effectiveness or stage of the disease, were analyzed for association with baseline BDQ resistance, acquired BDQ resistance, and treatment outcome. Among 39 patients, baseline BDQ resistance was 6% (2/33) by pDSTMGIT and 7% (2/29) by MIC7H11. All four baseline isolates with an Rv0678 mutation were phenotypically resistant. During treatment, 48% of the patients acquired BDQ resistance by pDSTMGIT, and 52% acquired mutations at various frequencies (97% in Rv0678). None of the factors significantly contributed to baseline or acquired BDQ resistance. Unfavorable treatment outcome (41%) was more frequent in the presence of acquired Rv0678 mutations [odds ratio (OR) 132, 95% confidence interval (CI) 7.43, 2375], phenotypic BDQ resistance (OR 176, 95% CI 6.48, 2423), or MIC increase above or below the critical concentration (both OR 84.3, 95% CI 2.93, 2423) during treatment. For these highly treatment-experienced patients, low baseline prevalence but high incidence of acquired BDQ resistance was observed. Acquisition of mutations in BDQ candidate resistance genes, regardless of their frequency, or increased MICs during treatment, even below the critical concentration, should be seen as a warning sign of resistance amplification and increased risk of unfavorable treatment outcome.
We performed a systematic review to generate evidence on the association between cumulative human immunodeficiency virus (HIV) viraemia and health outcomes.
METHODS
Quantitative studies reporting on HIV cumulative viraemia (CV) and its association with health outcomes among people living with HIV (PLHIV) on antiretroviral treatment (ART) were included. We searched MEDLINE via PubMed, Embase, Scopus and Web of Science and conference abstracts from 1 January 2008 to 1 August 2022.
RESULTS
The systematic review included 26 studies. The association between CV and mortality depended on the study population, methods used to calculate CV and its level. Higher CV was not consistently associated with greater risk of acquire immunodeficiency syndrome–defining clinical conditions. However, four studies present a strong relationship between CV and cardiovascular disease. The risk was not confirmed in relation of increased hazards of stroke. Studies that assessed the effect of CV on the risk of cancer reported a positive association between CV and malignancy, although the effect may differ for different types of cancer.
CONCLUSIONS
CV is associated with adverse health outcomes in PLHIV on ART, especially at higher levels. However, its role in clinical and programmatic monitoring and management of PLHIV on ART is yet to be established.
The burden of advanced HIV disease (AHD) and predictors of outcomes among people living with HIV (PLHIV) re-engaging in care are not well known.
METHODS
We conducted a retrospective cohort study of PLHIV who re-engaged in care after being lost to follow-up (LFU), from 2003 to 2019, in Myanmar. We calculated the incidence rates of attrition after re-engagement and performed Cox regression to identify risk factors for attrition.
RESULTS
Of 44 131 PLHIV who started antiretroviral treatment, 12 338 (28.0%) were LFU at least once: 7608 (61.6%) re-engaged in care, 4672 (61.4%) with AHD at re-engagement. The death and LFU rates were 2.21-fold (95% CI 1.82 to 2.67) and 1.46-fold (95% CI 1.33 to 1.61) higher among patients who re-engaged with AHD (p>0.001). Death in patients who re-engaged with AHD was associated with male sex (adjusted HR [aHR] 2.63; 95% CI 1.31 to 5.26; p=0.006), TB coinfection (aHR 2.26; 95% CI 1.23 to 4.14; p=0.008) and sex work (aHR 7.49, 95% CI 2.29 to 22.52; p<0.001). History of intravenous drug use was identified as a predictor of being LFU.
CONCLUSIONS
Re-engagement in HIV care in Myanmar is frequent and those who re-engage carry a high burden of AHD. As AHD at re-engagement is associated with higher attrition rates, implementation of differentiated interventions that enable earlier linkage to care and prompt identification and management of AHD in this population is necessary.
Despite HIV viral load (VL) monitoring being serial, most studies use a cross-sectional design to evaluate the virological status of a cohort. The objective of our study was to use a simplified approach to calculate viraemic-time: the proportion of follow-up time with unsuppressed VL above the limit of detection. We estimated risk factors for higher viraemic-time and whether viraemic-time predicted mortality in a second-line antiretroviral treatment (ART) cohort in Myanmar.
METHODS
We conducted a retrospective cohort analysis of people living with HIV (PLHIV) who received second-line ART for a period >6 months and who had at least two HIV VL test results between 01 January 2014 and 30 April 2018. Fractional logistic regression assessed risk factors for having higher viraemic-time and Cox proportional hazards regression assessed the association between viraemic-time and mortality. Kaplan-Meier curves were plotted to illustrate survival probability for different viraemic-time categories.
RESULTS
Among 1,352 participants, 815 (60.3%) never experienced viraemia, and 172 (12.7%), 214 (15.8%), and 80 (5.9%) participants were viraemic <20%, 20–49%, and 50–79% of their total follow-up time, respectively. Few (71; 5.3%) participants were ≥80% of their total follow-up time viraemic. The odds for having higher viraemic-time were higher among people with a history of injecting drug use (aOR 2.01, 95% CI 1.30–3.10, p = 0.002), sex workers (aOR 2.10, 95% CI 1.11–4.00, p = 0.02) and patients treated with lopinavir/ritonavir (vs. atazanavir; aOR 1.53, 95% CI 1.12–2.10, p = 0.008). Viraemic-time was strongly associated with mortality hazard among those with 50–79% and ≥80% viraemic-time (aHR 2.92, 95% CI 1.21–7.10, p = 0.02 and aHR 2.71, 95% CI 1.22–6.01, p = 0.01). This association was not observed in those with viraemic-time <50%.
CONCLUSIONS
Key populations were at risk for having a higher viraemic-time on second-line ART. Viraemic-time predicts clinical outcomes. Differentiated services should target subgroups at risk for a higher viraemic-time to control both HIV transmission and mortality.
A consequence of the West Africa Ebola outbreak 2014–2015 was the unprecedented number of Ebola survivors discharged from the Ebola Treatment Units (ETUs). Liberia alone counted over 5,000 survivors. We undertook a qualitative study in Monrovia to better understand the mental distress experienced by survivors during hospitalization and reintegration into their community.
METHODS
Purposively selected Ebola survivors from ELWA3, the largest ETU in Liberia, were invited to join focus group discussions. Verbal-informed consent was sought. Three focus groups with a total of 17 participants were conducted between February and April 2015. Thematic analysis approach was applied to analyze the data.
RESULTS
The main stressors inside the ETU were the daily exposure to corpses, which often remained several hours among the living; the patients’ isolation from their families and worries about their well-being; and sometimes, the perception of disrespect by ETU staff. However, most survivors reported how staff motivated patients to drink, eat, bathe, and walk. Additionally, employing survivors as staff fostered hope, calling patients by their name increased confidence and familiarity, and organizing prayer and singing activities brought comfort. When Ebola virus disease survivors returned home, the experience of being alive was both a gift and a burden. Flashbacks were common among survivors. Perceived as contagious, many were excluded from their family, professional, and social life. Some survivors faced divorce, were driven out of their houses, or lost their jobs. The subsequent isolation prevented survivors from picking up daily life, and the multiple losses affected their coping mechanisms. However, when available, the support of family, friends, and prayer enabled survivors to cope with their mental distress. For those excluded from society, psychosocial counseling and the survivor’s network were ways to give a meaning to life post-Ebola.
CONCLUSION
Exposure to death in the ETU and stigma in the communities induced posttraumatic stress reactions and symptoms of depression among Ebola survivors. Distress in the ETU can be reduced through timely management of corpses. Coping mechanisms can be strengthened through trust relationships, religion, peer/community support, and community-based psychosocial care. Mental health disorders need to be addressed with appropriate specialized care and follow-up.