Search

Abstract Background Patient-provider communication is a major challenge in resource-limited settings with large catchment areas. Though mobile phone usership increased 20-fold in Africa over the past decade, little is known about acceptability of, perceptions about disclosure and confidentiality, and preferences for cell phone communication of health information in the region. Methods We performed structured interviews of fifty patients at the Immune Suppression Syndrome clinic in Mbarara, Uganda to assess four domains of health-related communication: a) cell phone use practices and literacy, b) preferences for laboratory results communication, c) privacy and confidentiality, and d) acceptability of and preferences for text messaging to notify patients of abnormal test results. Results Participants had a median of 38 years, were 56% female, and were residents of a large catchment area throughout southwestern Uganda. All participants expressed interest in a service to receive information about laboratory results by cell phone text message, stating benefits of increased awareness of their health and decreased transportation costs. Ninety percent reported that they would not be concerned for unintended disclosure. A minority additionally expressed concerns about difficulty interpreting messages, discouragement upon learning bad news, and technical issues. Though all respondents expressed interest in password protection of messages, there was also a strong desire for direct messages to limit misinterpretation of information. Conclusions Cell phone text messaging for communication of abnormal laboratory results is highly acceptable in this cohort of HIV-infected patients in rural Uganda. The feasibility of text messaging, including an optimal balance between privacy and comprehension, should be further studied.

Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection with Mycobacterium tuberculosis (M.tb) by mechanisms that remain to be fully explained. We evaluated association between M.tb sensitization and T2DM among U.S adults and, via formal mediation analysis, the extent to which this association is mediated by insulin resistance and/or β-cell failure. These evaluations accounted for demographic, socio-economic, behavioral and clinical characteristics. T2DM was assessed by fasting plasma glucose, 2-hour oral glucose tolerance testing and HbA1c; homoeostasis model assessment 2 (HOMA2) was used to estimate β-cell dysfunction (HOMA2-B) and insulin resistance (HOMA2-IR); while M.tb sensitization status was ascertained by tuberculin skin testing (TST). Exposure to M.tb was associated with increased risk for T2DM, likely driven by an increase in insulin resistance. Definitive prospective studies examining incident T2DM following tuberculosis are warranted., Research in Context: What is already known about this subject?: Accumulating evidence suggests that pre-diabetes and new-onset type 2 diabetes mellitus (T2DM) may be a long-term complication of exposure to Mycobacterium tuberculosis ( M.tb ) via mechanisms that remain to be unraveled What is the key question?: To what extent do insulin resistance and β-cell failure mediate the association between M.tb sensitization with T2DM among US adults? What are the new findings?: M.tb sensitization is characterized by distinct glucose metabolic disturbances manifesting as increased risk of T2DM and isolated impaired fasting glucose (IFG) Insulin resistance, and not β-cell impairment, likely independently mediate the observed diabetogenic effects of M.tb sensitization How might this impact on clinical and/or public health practice in the foreseeable future?: If corroborated by prospective studies, both TB programs and individual clinical care must incorporate monitoring of serum glucose and long-term metabolic outcomesThis will be particularly urgent in sub-Saharan Africa and South-East Asia where scarce health resources coincide with overlapping endemic TB and epidemic T2DM.

It is unclear how rising obesity among people with HIV (PWH) in sub-Saharan Africa (SSA) impacts their risk of type 2 diabetes mellitus (diabetes). Using a South African national cross-sectional sample of adult PWH and their peers without HIV (PWOH), we examined the associations between HIV and prevalent diabetes across the spectrum of body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WtHR). Analyses were sex stratified, and adjusted for age, sociodemographic and behavioral factors. The prevalence of diabetes among males was similar between PWH and PWOH, overall and at all levels of adiposity. In contrast, overall diabetes prevalence was higher among female PWOH than female PWH. However, there were differences according to adiposity such that, compared to female PWOH, relative diabetes prevalence in female PWH was reduced with obesity but accentuated with leanness. These differences in the relationship between adiposity and diabetes by HIV serostatus call for better mechanistic understanding of sex-specific adipose tissue biology in HIV in South Africa, and possibly in other HIV endemic settings in SSA.

Metabolic disease is increasing in people with HIV (PWH) in South Africa, but little is known about self-perceptions of body size, health, and nutritional behavior in this population. We performed a cross-sectional analysis of individual-level data from the 2016 South Africa Demographic and Health Survey. This survey measured HIV serostatus and body mass index (BMI). We categorized participants into six BMI groups: 18.5-22 kg/m 2 , 22-25 kg/m 2 , 25-27.5 kg/m 2 , 27.5-30 kg/m 2 , 30-35 kg/m 2 , and ≥ 35 kg/m 2 and stratified them by HIV serostatus. Our outcomes were self-reported (1) body size and (2) health status among all participants, and intake of (3) chips and (4) sugar-sweetened beverages (SSB) in PWH. We described these metrics and used multivariable regression to evaluate the relationship between the nutritional behaviors and BMI ≥ 25 kg/m 2 in PWH only, adjusting for age, sex, educational attainment, and household wealth quintile. Of 6138 participants, 1163 (19.7%) were PWH. Among PWH, < 10% with a BMI 25-30 kg/m 2 , < 20% with a BMI 30-35 kg/m 2 and < 50% with a BMI ≥ 35 kg/m 2 self-reported as overweight or obese. PWH reported being in poor health at higher rates than those without HIV at each BMI category except ≥ 35 kg/m 2 . In adjusted models, SSB consumption was associated with BMI ≥ 25 kg/m 2 (1.13 [1.01-1.25], t-statistic = 2.14, p = 0.033) in PWH. Perceptions of body size may challenge efforts to prevent weight gain in PWH in South Africa. SSB intake reduction should be further explored as a modifiable risk factor for obesity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: Little is known about the impact of HIV infection on the clinical presentation and outcomes after stroke in the modern antiretroviral therapy (ART) era. We aimed to compare stroke characteristics and outcomes between persons with HIV (PWH) and without HIV (PWOH) presenting with stroke in Uganda., Methods: We conducted a matched cohort study at Mulago National Referral Hospital and Mbarara Regional Referral Hospital between January 2018 and November 2020. We enrolled consecutive PWH presenting with CT-confirmed acute or subacute stroke (symptom onset ≤14 days) and matched them by sex and stroke type to 2 consecutive available PWOH admitted to the same hospital. We obtained baseline clinical data and followed participants for 90 days from the day of clinical presentation. We compared stroke severity (defined by the NIH stroke scale [NIHSS]) and 90-day all-cause mortality and morbidity (using the modified Rankin Scale [mRS]) by HIV serostatus with and without adjustment for confounders., Results: We enrolled 105 PWH and 157 PWOH with stroke. PWH were younger (mean [SD] age 49 [14] vs 59 [16] years, p < 0.001), and nearly 80% (82/105) were on ART for a median of 5 years and a median CD4 count of 214 cells/uL (interquartile range 140, 337). Compared with PWOH, PWH presented with a 3-point lower median NIHSS (16 vs 19, p = 0.011), a 20% lower proportion of all-cause mortality at 90 days ( p = 0.001), and had less disability at 90 days (median mRS 4 vs 5, p = 0.004). Age and NIHSS-adjusted odds ratio of 90-day all-cause mortality in PWH compared with PWOH was 0.45 (95% CI 0.22-0.96, p = 0.037)., Discussion: In the modern ART era, PWH with acute stroke in Uganda present with modest stroke and are significantly less likely to die within 90 days than PWOH. This potentially reflects the protective effects of ART, enhanced health care access, and their younger age at stroke presentation., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp. TAKE-HOME POINTS → In the antiretroviral therapy era, people with HIV presenting with stroke in Uganda now tend to be on antiretroviral therapy for many years, although persistently low CD4 counts are common in this population.→ People without HIV present with more severe strokes than people with HIV in Uganda, as evidenced by a higher median NIH Stroke Scale score.→ Stroke outcomes are poor overall with a mortality rate at 90 days of 40% in the entire cohort.→ Compared with people with HIV infection, those without HIV infection have higher all-cause mortality and greater disability 90 days after stroke., (© 2023 American Academy of Neurology.)

Despite the scale-up of antiretroviral therapy (ART) in South Africa, HIV-1 incidence remains high. The anticipated use of potent integrase strand transfer inhibitors and long-acting injectables aims to enhance viral suppression at the population level and diminish transmission. Nevertheless, pre-existing drug resistance could impede the efficacy of long-acting injectable ART combinations, such as rilpivirine (an NNRTI) and cabotegravir (an INSTI). Consequently, a thorough understanding of transmission networks and geospatial distributions is vital for tailored interventions, including pre-exposure prophylaxis with long-acting injectables. However, empirical data on background resistance and transmission networks remain limited. In a community-based study in rural KwaZulu-Natal (2018-2019), prior to the widespread use of integrase inhibitor-based first-line ART, we performed HIV testing with reflex HIV-1 RNA viral load quantification on 18,025 participants. From this cohort, 6,096 (33.9%) tested positive for HIV via ELISA, with 1,323 (21.7%) exhibiting detectable viral loads (> 40 copies/mL). Of those with detectable viral loads, 62.1% were ART-naïve, and the majority of the treated were on an efavirenz + cytosine analogue + tenofovir regimen. Deep sequencing analysis, with a variant abundance threshold of 20%, revealed NRTI resistance mutations such as M184V in 2% of ART-naïve and 32% of treated individuals. Tenofovir resistance mutations K65R and K70E were found in 12% and 5% of ART-experienced individuals, respectively, and in less than 1% of ART-naïve individuals. Integrase inhibitor resistance mutations were notably infrequent (< 1%). Prevalence of pre-treatment drug resistance to NNRTIs was 10%, predominantly consisting of the K103N mutation. Among those with viraemic ART, NNRTI resistance was 50%, with rilpivirine-associated mutations observed in 9% of treated and 6% of untreated individuals. Cluster analysis revealed that 20% (205/1,050) of those sequenced were part of a cluster. We identified 171 groups with at least two linked participants; three quarters of clusters had only two individuals, and a quarter had 3-6 individuals. Integrating phylogenetic with geospatial analyses, we revealed a complex transmission network with significant clustering in specific regions, notably peripheral and rural areas. These findings derived from population scale genomic analyses are encouraging in terms of the limited resistance to DTG, but indicate that transitioning to long-acting cabotegravir + rilpivirine for transmission reduction should be accompanied by prior screening for rilpivirine resistance. Whole HIV-1 genome sequencing allowed identification of significant proportions of clusters with multiple individuals, and geospatial analyses suggesting decentralised networks can inform targeting public health interventions to effectively curb HIV-1 transmission.

Background: Incomplete antiretroviral therapy (ART) adherence has been linked to deleterious immunologic, inflammatory, and clinical consequences, even among virally suppressed (<50 copies/mL) persons with human immunodeficiency virus (PWH). The impact of improving adherence in the risk of severe non-AIDS events (SNAEs) and death in this population is unknown., Methods: We estimated the reduction in the risk of SNAEs or death resulting from an increase in ART adherence by (1) applying existing data on the association between adherence with high residual inflammation/coagulopathy in virally suppressed PWH, and (2) using a Cox proportional hazards model derived from changes in plasma interleukin 6 (IL-6) and D-dimer from 3 randomized clinical trials. Comparatively, assuming 100% ART adherence in a PWH who achieves viral suppression, we estimated the number of persons in whom a decrease in adherence to <100% would need to be observed for an additional SNAE or death event to occur during 3- and 5-year follow-up., Results: Increasing ART adherence to 100% in PWH who are suppressed on ART despite imperfect adherence translated into a 6%-37% reduction in the risk of SNAEs or death. Comparatively, based on an anticipated 12% increase in IL-6, 254 and 165 PWH would need to decrease their adherence from 100% to <100% for an additional event to occur over 3- and 5-year follow-up, respectively., Conclusions: Modest gains in ART adherence could have clinical benefits beyond virologic suppression. Increasing ART adherence (eg, via an intervention or switch to long-acting ART) in PWH who remain virally suppressed despite incomplete adherence should be evaluated., Competing Interests: Potential conflicts of interest. J. R. C.-M. has received research support (investigator initiated) from Gilead Sciences, paid to his institution. M. C.'s institution has received research grants from Gilead, MSD, and ViiV Healthcare and travel grants from Gilead. S. S.-V. has received research grants from Gilead Sciences and MSD, and nonfinancial support from Gilead Sciences and ViiV Healthcare. J. E. H. has been a paid consultant for Merck and owns stock in Natera. T. T. B. has served as consultant to Merck, ViiV Healthcare, and Janssen. C. C is a full-time employee of Gilead Sciences. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Over the past decade, 15 high-priority countries in eastern and southern Africa have promoted voluntary medical male circucmsion for HIV and STI prevention. Despite male circumcision prevalence in Uganda nearly doubling from 26% in 2011 to 43% in 2016, it remained below the target level by 2020. Little is known about perceived norms of male circumcision and their association with circumcision uptake among men., Methods: We conducted a cross-sectional study targeting all adult residents across eight villages in Rwampara District, southwestern Uganda in 2020-2022. We compared what men and women reported as the adult male circumcision prevalence within their village (perceived norm: >50% (most), 10% to <50% (some), <10%, (few), or do not know) to the aggregated prevalence of circumcision as reported by men aged <50 years. We used a modified multivariable Poisson regression model to estimate the association between perceived norms about male circumcision uptake and personal circumcision status among men., Results: Overall, 167 (38%) men < 50 years old were circumcised (and 27% of all men were circumcised). Among all 1566 participants (91% response rate), 189 (27%) men and 177 (20%) women underestimated the male circumcision prevalence, thinking that few men in their own village had been circumcised. Additionally, 10% of men and 25% of women reported not knowing the prevalence. Men who underestimated the prevalence were less likely to be circumcised (aRR = 0.51, 95% CI 0.37 to 0.83) compared to those who thought that some village men were circumcised, adjusting for perceived personal risk of HIV, whether any same-household women thought most men were circumcised, and other sociodemographic factors., Conclusions: Across eight villages, a quarter of the population underestimated the local prevalence of male circumcision. Men who underestimated circumcision uptake were less likely to be circumcised. Future research should evaluate norms-based approaches to promoting male circumcision uptake. Strategies may include disseminating messages about the increasing prevalence of adult male circumcision uptake in Uganda and providing personalized normative feedback to men who underestimated local rates about how uptake is greater than they thought.

Background: Antiretroviral therapy (ART) has led to an increased lifespan for people living with HIV (PWH). This increased lifespan, coupled with the effects of HIV and adverse effects of ART have resulted in an increasing burden of cardiometabolic disease (CMD) among PWH. Physical activity (PA) has been proposed as an effective strategy to reduce the risk of developing cardiometabolic disease and other health complications in PWH. The aim of this paper is to review the characteristics and efficacy of PA interventions to improve cardiometabolic and psychosocial outcomes among PWH in sub-Saharan Africa., Methods: The review will follow the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P). Literature searches will be conducted in PubMed, Web of Science (WoS), African Index Medicus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Embase. Peer-reviewed publications will be included if they include adults (age 18 or older), PWH in sub-Saharan Africa, and a PA intervention to improve cardiometabolic outcomes and/or psychosocial outcomes. We will include randomized controlled trials and quasi-experimental study designs. Two independent reviewers will screen all abstracts and full-text articles. The study methodological quality (or bias) will be appraised using the Revised tool to assess risk of bias in randomized trials and the Downs and Black checklist. Certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation guidelines. Meta-analyses will be conducted if our results are adequate for meta-analysis. Outcomes will be analyzed as continuous or dichotomous and meta-analyses will be conducted using random effects models with Stata computer software., Discussion: This review will identify and synthesize the current evidence regarding the characteristics and efficacy of PA interventions to improve cardiometabolic and psychosocial outcomes among PWH in sub-Saharan Africa. We also plan to identify the strengths and weaknesses of evaluated interventions. Based on the evidence, recommendations will be made to promote the design and further evaluate the most promising strategies to maximize the efficacy of PA interventions in improving cardiometabolic and psychosocial outcomes in PWH in sub-Saharan Africa., Systematic Review Registration: PROSPERO registration ID: CRD42021271937., (© 2023. The Author(s).)

Competing Interests: Competing interests: GK has a family financial interest in a global health technology company, Dimagi. KR receives royalties from UpToDate, for authorship of an article about electronic cigarettes. NAR receives royalties from UpToDate for writing about smoking cessation topics and is a consultant for Achieve Life Sciences regarding an investigational smoking cessation medication.

Competing Interests: FV reports grants from the US Agency of International Development, Unitaid, AIDS Fonds, and the South African Medical Research Council; non-financial support from Gilead, ViiV Healthcare, and MSD; personal fees from Gilead, ViiV, Mylan, Merk, Adcock-Ingram, Aspen, Abbott, Roche, Johnson & Johnson, Virology Education; and other support from Merck and Johnson & Johnson, outside the submitted work. All other authors declare no competing interests. The findings and conclusions in this systematic review are those of the authors and do not necessarily represent the official position of the funding agencies. This work has been supported by the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.

Background: The late recognition of virologic failure (VF) places persons with HIV in Sub-Saharan Africa at risk for HIV transmission, disease progression, and death. We conducted a systematic review and meta-analysis to determine if the recognition and response to VF in the region has improved., Methods: We searched for studies reporting CD4 count at confirmed VF or at switch to second-line antiretroviral therapy (ART). Using a random-effects metaregression model, we analyzed temporal trends in CD4 count at VF-or at second-line ART switch-over time. We also explored temporal trends in delay between VF and switch to second-line ART., Results: We identified 26 studies enrolling patients with VF and 10 enrolling patients at second-line ART switch. For studies that enrolled patients at VF, pooled mean CD4 cell count at failure was 187 cells/mm 3 (95% CI, 111 to 263). There was no significant change in CD4 count at confirmed failure over time (+4 cells/year; 95% CI, -7 to 15). Among studies that enrolled patients at second-line switch, the pooled mean CD4 count was 108 cells/mm 3 (95% CI, 63 to 154). CD4 count at switch increased slightly over time (+10 CD4 cells/year; 95% CI, 2 to 19). During the same period, the mean delay between confirmation of VF and switch was 530 days, with no significant decline over time (-14 days/year; 95% CI, -58 to 52)., Conclusions: VF in Africa remains an event recognized late in HIV infection, a problem compounded by ongoing delays between VF and second-line switch., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Obesity is common among people living with HIV (PLWH) and early-stage infection, yet associations with combination antiretroviral (cART) adherence are unclear., Methods: Among PLWH initiating cART in Uganda and South Africa, body mass index (BMI) was assessed at cART initiation, and cART adherence was monitored in real-time over 12 months. The association of obesity (BMI ≥ 30 kg/m 2 ) with adherence was assessed among nonpregnant participants with CD4 > 350 cells/mm 3 using fractional regression modeling., Results: Among 322 participants, median age was 32 years, 70% were female, and 54% were from Uganda. Prevalence of obesity was 12% in Uganda and 28% in South Africa. Mean overall cART adherence was 83% in Uganda and 66% in South Africa. Participants with obesity had higher adherence than those without obesity: +3.6% (p = 0.44) in Uganda and +11.4% (p = 0.02) in South Africa., Conclusion: Obesity at cART initiation was common and associated with higher adherence, although only significantly in South Africa., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: In low- and middle-income settings, obtaining informed consent for biobanking may be complicated by socio-economic vulnerability and context-specific power dynamics. We explored participants experiences and perceptions of the research objectives in a community-based multidisease screening and biospecimen collection platform in rural KwaZulu-Natal, South Africa., Methods: We undertook semi-structured in-depth interviews to assess participant understanding of the informed consent, research objectives and motivation for participation., Results: Thirty-nine people participated (individuals who participated in screening/biospecimen collection and those who did not and members of the research team). Some participants said they understood the information shared with them. Some said they participated due to the perceived benefits of the reimbursement and convenience of free healthcare. Most who did not participate said it was due to logistical rather than ethical concerns. None of the participants recalled aspects of biobanking and genetics from the consent process., Conclusions: Although most people understood the study objectives, we observed challenges to identifying language appropriate to explain biobanking and genetic testing to our target population. Engagement with communities to adopt contextually relevant terminologies that participants can understand is crucial. Researchers need to be mindful of the impact of communities' socio-economic status and how compensation can be potentially coercive., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Introduction: Antiretroviral therapy (ART) has revolutionised the care of HIV-positive individuals resulting in marked decreases in morbidity and mortality, and markedly reduced transmission to sexual partners. However, these benefits can only be realised if individuals are aware of their HIV-positive status, initiated and retained on suppressive lifelong ART. Framed using the socio-ecological model, the present study explores factors contributing to poor ART uptake among community members despite high acceptance of HIV-testing within a Treatment as Prevention (TasP) trial. In this paper we identify barriers and facilitators to treatment across different levels of the socio-ecological framework covering individual, community and health system components., Methods: This research was embedded within a cluster-randomised trial (ClinicalTrials.gov, number NCT01509508) of HIV treatment as Prevention in rural KwaZulu-Natal, South Africa. Data were collected between January 2013 and July 2014 from resident community members. Ten participants contributed to repeat in-depth interviews whilst 42 participants took part in repeat focus group discussions. Data from individual interviews and focus group discussions were triangulated using community walks to give insights into community members' perception of the barriers and facilitators of ART uptake. We used thematic analysis guided by a socio-ecological framework to analyse participants' narratives from both individual interviews and focus group discussions., Results: Barriers and facilitators operating at the individual, community and health system levels influence ART uptake. Stigma was an over-arching barrier, across all three levels and expressed variably as fear of HIV disclosure, concerns about segregated HIV clinical services and negative community religious perceptions. Other barriers were individual (substance misuse, fear of ART side effects), community (alternative health beliefs). Facilitators cited by participants included individual (expectations of improved health and longer life expectancy following ART, single tablet regimens), community (availability of ART in the community through mobile trial facilities) and health system factors (fast and efficient service provided by friendly staff)., Discussion: We identified multiple barriers to achieving universal ART uptake. To enhance uptake in HIV care services, and achieve the full benefits of ART requires interventions that tackle persistent HIV stigma, and offer people with HIV respectful, convenient and efficient services. These interventions require evaluation in appropriately designed studies., Competing Interests: I have updated the competing interest statement in the text of the manuscript. Revised text below I have read the journal's policy and the authors of this manuscript have the following competing interests: CI received research grants, honoraria for consulting services and conference attendance support from Gilead Sciences. All other authors declare that they have no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: There is limited literature on the appropriateness of viral load (VL) monitoring and management of detectable VL in public health settings in rural South Africa., Methods: We analysed data captured in the electronic patient register from HIV-positive patients ≥ 15 years old initiating antiretroviral therapy (ART) in 17 public sector clinics in rural KwaZulu-Natal, during 2010-2016. We estimated the completion rate for VL monitoring at 6, 12, and 24 months. We described the cascade of care for those with any VL measurement ≥ 1000 HIV-1 RNA copies/mL after ≥ 20 weeks on ART, including the following proportions: (1) repeat VL within 6 months; (2) re-suppressed; (3) switched to second-line regimen., Results: There were 29 384 individuals who initiated ART during the period [69% female, median age 31 years (interquartile range 25-39)]. Of those in care at 6, 12, and 24 months, 40.7% (9861/24 199), 34% (7765/22 807), and 25.5% (4334/16 965) had a VL test at each recommended time-point, respectively. The VL results were documented at all recommended time-points for 12% (2730/22 807) and 6.2% (1054/16 965) of ART-treated patients for 12 and 24 months, respectively. Only 391 (18.3%) of 2135 individuals with VL ≥ 1000 copies/mL on first-line ART had a repeat VL documenting re-suppression or were appropriately changed to second-line with persistent failure. Completion of the treatment failure cascade occurred a median of 338 days after failure was detected., Conclusion: We found suboptimal VL monitoring and poor responses to virologic failure in public-sector ART clinics in rural South Arica. Implications include increased likelihood of morbidity and transmission of drug-resistant HIV., (© 2020 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Over the past decade, there has been a massive scale-up of primary and secondary prevention services to reduce the population-wide incidence of HIV. However, the impact of these services on HIV incidence has not been demonstrated using a prospectively followed, population-based cohort from South Africa-the country with the world's highest rate of new infections. To quantify HIV incidence trends in a hyperendemic population, we tested a cohort of 22,239 uninfected participants over 92,877 person-years of observation. We report a 43% decline in the overall incidence rate between 2012 and 2017, from 4.0 to 2.3 seroconversion events per 100 person-years. Men experienced an earlier and larger incidence decline than women (59% vs. 37% reduction), which is consistent with male circumcision scale-up and higher levels of female antiretroviral therapy coverage. Additional efforts are needed to get more men onto consistent, suppressive treatment so that new HIV infections can be reduced among women.

Objectives: The aim of the study was to estimate rates of linkage to HIV care and antiretroviral treatment (ART) initiation after the introduction of home-based HIV counselling and testing (HBHCT) and telephone-facilitated support for linkage in rural South Africa., Methods: A population-based prospective cohort study was carried out in KwaZulu Natal, South Africa. All residents aged ≥ 15 years were eligible for HBHCT. Those who tested positive and were not in care were referred for ART at one of 11 public-sector clinics. Individuals who did not attend the clinic within 2 weeks were sent a short message service (SMS) reminder; those who had not attended after a further 2 weeks were telephoned by a nurse counsellor, to discuss concerns and encourage linkage. Kaplan-Meier methods were used to estimate the proportion of newly diagnosed individuals linking to care and initiating ART., Results: Among 38 827 individuals visited, 26% accepted HBHCT. Uptake was higher in women than in men (30% versus 20%, respectively), but similar in people aged < 30 years and ≥ 30 years (28% versus 26%, respectively). A total of 784 (8%) tested HIV positive, of whom 427 (54%) were newly diagnosed. Within 6 months, 31% of women and 18% of men < 30 years old had linked to care, and 29% and 16%, respectively, had started ART. Among those ≥ 30 years, 41% of women and 38% of men had linked to care within 6 months, and 41% and 35%, respectively, had started ART., Conclusions: Despite facilitated linkage, rates of timely linkage to care and ART initiation after HBHCT were very low, particularly among young men. Innovations are needed to provide effective HIV care and prevention interventions to young people, and thus maximize the benefits of universal test and treat., (© 2019 British HIV Association.)

Introduction: Africa contributes little to the biomedical literature despite its high burden of infectious diseases. Global health research partnerships aimed at addressing Africa-endemic disease may be polarised. Therefore, we assessed the contribution of researchers in Africa to research on six infectious diseases., Methods: We reviewed publications on HIV and malaria (2013-2016), tuberculosis (2014-2016), salmonellosis, Ebola haemorrhagic fever and Buruli ulcer disease (1980-2016) conducted in Africa and indexed in the PubMed database using Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Papers reporting original research done in Africa with at least one laboratory test performed on biological samples were included. We studied African author proportion and placement per study type, disease, funding, study country and lingua franca., Results: We included 1182 of 2871 retrieved articles that met the inclusion criteria. Of these, 1109 (93.2%) had at least one Africa-based author, 552 (49.8%) had an African first author and 41.3% (n=458) an African last author. Papers on salmonellosis and tuberculosis had a higher proportion of African last authors (p<0.001) compared with the other diseases. Most of African first and last authors had an affiliation from an Anglophone country. HIV, malaria, tuberculosis and Ebola had the most extramurally funded studies (≥70%), but less than 10% of the acknowledged funding was from an African funder., Conclusion: African researchers are under-represented in first and last authorship positions in papers published from research done in Africa. This calls for greater investment in capacity building and equitable research partnerships at every level of the global health community., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There is increasing interest in home based testing and treatment of HIV to expand access to treatment in sub-Saharan Africa. Such programs rely on self-reported HIV history and use of antiretroviral therapy (ART). However, the accuracy of self-reported ART use in community settings is not well described. In this study, we compared self-reported ART (SR-ART) use in a home based survey against biological exposure to ART (BE-ART), in a population study of older adults in South Africa. Health and Aging in Africa: a Longitudinal Study of an INDEPTH community in South Africa (HAALSI) is a cohort of adults aged 40 +. The baseline home-based interview included self-reported HIV status and ART use. All participants also underwent biological testing for HIV antibodies, viral load and exposure to emtricitabine (FTC) or lamivudine (3TC), which are included in all first-line and second-line ART regimens in the public-sector South African HIV program. We calculated the performance characteristics for SR-ART compared to BE-ART and fit multivariable logistic regression models to identify correlates of invalid SR-ART responses. Of 4560 HAALSI participants with a valid HIV test result available, 1048 (23%) were HIV-positive and 734 [70% of people living with HIV (PLWH)] were biologically validated ART users (BE-ART). The sensitivity of SR-ART use was 64% (95% CI 61-68%) and the specificity was 94% (95% CI 91-96%); the positive predictive value (PPV) was 96% (95% CI 94-98%) and negative predictive value (NPV) was 52% (95% CI 48-56%). We found no sociodemographic predictors of accurate SR-ART use. Over one in three individuals with detectable ART in their blood denied current ART use during a home-based interview. These results demonstrate ongoing stigma related to HIV and its treatment, and have important implications for community health worker programs, clinical programs, and research studies planning community-based ART initiation in the region.

We conducted a cross-sectional study of 148 HIV+ on HIV antiretroviral therapy and 149 HIV- adults in Mbarara, Uganda, to estimate the association between HIV infection and homeostasis model assessment of insulin resistance (HOMA-IR) using multivariable regression analysis. In addition, we evaluated whether intestinal fatty acid-binding protein (I-FABP), monocyte activation markers soluble (s)CD14 and sCD163, and proinflammatory cytokine interleukin 6 (IL-6) mediated this association. HOMA-IR was greater among HIV+ than HIV- adults [median (interquartile range): 1.3 (0.7-2.5) vs. 0.9 (0.5-2.4); p  = 0.008]. In models adjusted for sociodemographic variables, diet, hypertension, and smoking history, HIV infection was associated with 37% [95% confidence intervals (95% CIs): 5-77] greater HOMA-IR compared with HIV- participants. The magnitude of association was greater when I-FABP was included as a covariate although the additive effect was modest (40% CI: 8-82). By contrast adding sCD14 to the model was associated with greater HOMA-IR (59%; 95% CI: 21-109) among HIV+ participants compared with HIV- participants. Among HIV+ participants, greater CD4 nadir was non-significantly associated with greater HOMA-IR (22%; 95% CI: -2 to 52). Each 5-unit increase in body mass index (BMI; 49% greater HOMA-IR; 95% CI: 18-87) and female sex (71%; 95% CI: 17-150) remained associated in adjusted models. In this study of mainly normal-weight Ugandan adults, HIV infection, female sex, and greater BMI were all associated with greater insulin resistance (IR). This association was strengthened modestly after adjustment for sCD14, suggesting possible distinct immune pathways to IR that are independent of HIV or related to inflammatory changes occurring on HIV treatment.

Objective: To move closer to achieving the third target of the UNAIDS 90-90-90 goals, we prospectively implemented a viral load (VL) champion (VLC) program aimed at enhancing VL monitoring and recognition of treatment failure. Design: Three clinics in eThekwini, Kwa-Zulu Natal (low-, medium- and high-volume, encompassing 9184 patients overall) were each assigned a VLC. We employed a descriptive analysis (chart audit) to compare the pre-intervention period to a 1-year post-intervention period. The number of patients with a VL test performed 6 and 12 months after the intervention was calculated as a proportion of VL tests due at those time points (VL completion rate). Results: The pre-implementation VL completion rate at the three sites was respectively 68% (140/205 patients), 54% (84/155 patients) and 64% (323/504 patients), and the 6-month post-implementation completion rate increased to 83% (995/1194 patients), 90% (793/878 patients) and 99% (3101/3124 patients) ( P < 0.0001 for each site). VL completion rates remained significantly higher at 12 months post-implementation, with an average cumulative VL completion rate of >90% across all facilities. Conclusion: We demonstrate a successful, multifaceted, quality-improvement intervention centered on a clinic-level VLC which, taken to scale, has important implications for attaining the third UNAIDS 90-90-90 target., Competing Interests: Conflicts of interest: none declared.

Hepatitis B virus (HBV) infection is hyperendemic in Cameroon, and healthcare workers (HCWs) are at high risk of infection. We aimed to assess prevalence, risk factors and vaccine coverage of HBV infection among HCWs in Cameroon. We conducted a cross-sectional study in 16 hospitals across all regions of Cameroon. HCWs were tested for HBV using rapid diagnostic tests (RDT). We collected data on socio-demographics and HBV vaccination status. We estimated prevalence of HBV and used Poisson regression models with robust standard errors to model the prevalence ratios of HBV positivity between covariates. We enrolled 1824 of 1836 eligible HCWs (97.5%). The mean age was 34 (SD: 10) years, 65.3% (n = 1787) were women, and 11.4% (n = 1747) had three or more doses of the HBV vaccine. Overall, we found a HBV prevalence of 8.7% (95% CI: 5.2%-14.3%). Patient transporters had the highest crude prevalence (14.3%; 95%CI: 5.4%-32.9%), whereas medical doctors had the lowest (3.2%; 95%CI: 0.8%-12.1%). The Far North Region had the highest prevalence of HBV (24.0%; 95%CI: 18.3%-30.8%). HBV prevalence decreased with increasing doses of the HBV vaccine (10.3% for no doses vs 3.5% for three or more doses; P < 0.001). In conclusion, approximately 1 in 12 HCWs in Cameroon have evidence of HBV infection, yet fewer than 1 in 6 have been fully vaccinated. Our results illustrate the urgent need to scale up systematic HBV screening and targeted vaccination of HCWs in the region., (© 2018 John Wiley & Sons Ltd.)

Competing Interests: Competing interests: None declared.

Objective: Diagnosis of bacterial meningitis often requires cytometry, chemistry and/or microbiologic culture capabilities. Unfortunately, laboratory resources in low-resource settings (LRS) often lack the capacity to perform these studies. We sought to determine whether the presence of white blood cells in CSF detected by commercially available urine reagent strips could aid in the diagnosis of bacterial meningitis., Methods: We searched PubMed for studies published between 1980 and 2016 that investigated the use of urine reagent strips to identify cerebrospinal fluid (CSF) pleocytosis. We assessed studies in any language that enrolled subjects who underwent lumbar puncture and had cerebrospinal fluid testing by both standard laboratory assays and urine reagent strips. We abstracted true-positive, false-negative, false-positive and true-negative counts for each study using a diagnostic threshold of ≥10 white blood cells per microlitre for suspected bacterial meningitis and performed mixed regression modelling with random effects to estimate pooled diagnostic accuracy across studies., Results: Our search returned 13 studies including 2235 participants. Urine reagent strips detected CSF pleocytosis with a pooled sensitivity of 92% (95% CI: 84-96), a pooled specificity of 98% (95% CI: 94-99) and a negative predictive value of 99% when the bacterial meningitis prevalence is 10%., Conclusions: Urine reagent strips could provide a rapid and accurate tool to detect CSF pleocytosis, which, if negative, can be used to exclude diagnosis of bacterial meningitis in settings without laboratory infrastructure. Further investigation of the diagnostic value of using protein, glucose and bacteria components of these strips is warranted., (© 2017 John Wiley & Sons Ltd.)

Background: In 2008, researchers reported that Timothy Brown (the 'Berlin Patient'), a man with HIV infection and leukemia, received a stem-cell transplant that removed HIV from his body as far as can be detected. In 2013, an infant born with HIV infection received anti-retroviral treatment shortly after birth, but was then lost to the health care system for the next six months. When tested for HIV upon return, the child (the 'Mississippi Baby') had no detectable viral load despite cessation of treatment. These remarkable clinical developments have helped reinvigorate the field of 'HIV cure' research., Discussion: Although this research field is largely in a pre-clinical phase, talk about curing HIV has become a regular feature in the global mass media. This paper explores the language of HIV cure from philosophical, ethical and historical perspectives. Examination of currently influential definitions of 'functional' and 'sterilizing' HIV cure reveal that these conceptualizations are more complicated than they seem. Cure is often understood in narrowly biomedical terms in isolation from the social and psychological dimensions of illness. Contemporary notions of HIV cure also inherit some of the epistemic problems traditionally associated with cures for other health conditions, such as cancer. Efforts to gain greater conceptual clarity about cure lead to the normative question of how 'HIV cure research' ought to be talked about., Summary: We argue that attention to basic concepts ethically matter in this context, and identify advantages as well as potential pitfalls of how different HIV/AIDS stakeholders may make use of the concept of cure. While concepts other than cure (such as remission) may be appropriate in clinical contexts, use of the word cure may be justified for other important purposes in the struggle against HIV/AIDS.

Background: Less than one-third of HIV-infected pregnant women eligible for combination antiretroviral therapy (ART) globally initiate treatment prior to delivery, with lack of access to timely CD4 results being a principal barrier. We evaluated the effectiveness of an SMS-based intervention to improve access to timely antenatal ART., Methods: We conducted a stepped-wedge cluster randomized trial of a low-cost programmatic intervention in 20 antenatal clinics in Gaborone, Botswana. From July 2011-April 2012, 2 clinics were randomly selected every 4 weeks to receive an ongoing clinic-based educational intervention to improve CD4 collection and to receive CD4 results via an automated SMS platform with active patient tracing. CD4 testing before 26 weeks gestation and ART initiation before 30 weeks gestation were assessed., Results: Three-hundred-sixty-six ART-naïve women were included, 189 registering for antenatal care under Intervention and 177 under Usual Care periods. Of CD4-eligible women, 100 (59.2%) women under Intervention and 79 (50.6%) women under Usual Care completed CD4 phlebotomy before 26 weeks gestation, adjusted odds ratio (aOR, adjusted for time that a clinic initiated Intervention) 0.87 (95% confidence interval [CI]0.47-1.63, P = 0.67). The SMS-based platform reduced time to clinic receipt of CD4 test result from median of 16 to 6 days (P<0.001), was appreciated by clinic staff, and was associated with reduced operational cost. However, rates of ART initiation remained low, with 56 (36.4%) women registering under Intervention versus 37 (24.2%) women under Usual Care initiating ART prior to 30 weeks gestation, aOR 1.06 (95%CI 0.53-2.13, P = 0.87)., Conclusions: The augmented SMS-based intervention delivered CD4 results more rapidly and efficiently, and this type of SMS-based results delivery platform may be useful for a variety of tests and settings. However, the intervention did not appear to improve access to timely antenatal CD4 testing or ART initiation, as obstacles other than CD4 impeded ART initiation during pregnancy.

Background: Point-of-care tests have the capacity to improve healthcare delivery by reducing costs and delay associated with care. A novel point-of-care immunochromatographic test for dual diagnosis of both HIV and syphilis by detecting IgG, IgM and IgA antibodies to HIV, and specific and recombinant Treponema pallidum antigens has recently been developed, but has not been evaluated in rural field settings. We evaluated the performance of the SD Bioline Syphilis/HIV Duo (Duo) assay at a healthcare center in rural Uganda., Methods: A convenience sample of pregnant women attending Kinoni Health Centre IV from March to May, 2013 was enrolled. Venous blood was collected and centrifuged for plasma isolation. Samples were tested with the Duo assay and compared with the Treponema pallidum hemaglutination assay and paired HIV rapid antibody tests as the reference standards. The ease of use and time required for the Duo assay were also assessed by laboratory technicians., Results: Two hundred twenty women were enrolled with a mean age of 25.00 years (SD 5.41). The sensitivity and specificity of the Duo assay were 100% (95% CI 79.0 - 100%) and 100% (95% CI 97.6 - 100.0) respectively, for syphilis, and, 100% (75.9 - 100%) and 99.5% (96.8 - 99.9%) respectively, for HIV. The duo kit was found to be faster and easier to use than the current HIV and syphilis testing techniques., Conclusion: The sensitivity and specificity of the SD Bioline HIV/Syphilis Duo test were excellent in a field setting in Uganda. The Duo assay should be further evaluated in alternate populations and with point-of-care specimens (e.g. whole blood from finger stick specimens), but shows promise as a tool for improved HIV and syphilis surveillance, diagnosis, and treatment in field settings.

Background: The resazurin microtiter assay (classic REMA), a colorimetric liquid culture-based drug susceptibility assay for Mycobacterium tuberculosis (MTB), has been endorsed by the World Health Organization. The assay requires 8-16 days to obtain results, delaying management of drug resistant tuberculosis patients. A modified REMA which allows results in as little as 24 hours for bacterial strains, has been developed and validated using Staphylococcus aureus, but has not yet been evaluated for MTB. Therefore we assessed the performance of the modified REMA for rifampicin (RIF) and isoniazid (INH) susceptibility, using the classic REMA as the reference standard. We also compared simplicity (from the technicians' point of view), time taken to obtain results (rank-sum testing), specificity and Kappa statistics of the two methods., Results: The modified REMA, which is a one-step procedure, was found to be simpler to perform and results were obtained in a significantly shorter time (5 versus 9 days, p < 0.0001) compared to the classic REMA due to addition of indicator and strain at the same time. The specificity of the modified REMA was low {46.8% (35.5% - 58.4%) for RIF and 13.9% (7.2% - 23.5%) for INH}. Kappa statistics were 16.0% for RIF and 2.0% for INH. Low specificity and kappa statistics are due to indicator reduction by the strains before complete drug activity., Conclusion: Although modified REMA is faster and simpler compared to classic REMA, it is not reliable for MTB drug susceptibility testing.

A real-time wireless electronic adherence monitor (EAM) and weekly self-report of missed doses via interactive voice response (IVR) and short message service (SMS) queries were used to measure antiretroviral therapy adherence in 49 adults and 46 children in rural Uganda. Median adherence was 89.5% among adults and 92.8% among children by EAM, and 99-100% for both adults and children by IVR/SMS self-report. Loss of viral suppression was significantly associated with adherence by EAM (odds ratio 0.58 for each 10% increase), but not IVR/SMS. Wireless EAM creates an exciting opportunity to monitor and potentially intervene with adherence challenges as they are happening.

Optimal tuberculosis testing usually involves sputum centrifugation followed by broth culture. However, centrifuges are biohazardous and scarce in the resource-limited settings where most tuberculosis occurs. To optimize tuberculosis testing for these settings, centrifugation of 111 decontaminated sputum samples was compared with syringe-aspiration through polycarbonate membrane-filters that were then cultured in broth. To reduce the workload of repeated microscopic screening of broth cultures for tuberculosis growth, the colorimetric redox indicator 2,3-diphenyl-5-(2-thienyl) tetrazolium chloride was added to the broth, which enabled naked-eye detection of culture positivity. This combination of filtration and colorimetric growth-detection gave similar results to sputum centrifugation followed by culture microscopy regarding mean colony counts (43 versus 48; P = 0.6), contamination rates (0.9% versus 1.8%; P = 0.3), and sensitivity (94% versus 95%; P = 0.7), suggesting equivalency of the two methods. By obviating centrifugation and repeated microscopic screening of cultures, this approach may constitute a more appropriate technology for rapid and sensitive tuberculosis diagnosis in basic laboratories.

Although Hodgkin and Reed-Sternberg (HRS) cells are B lymphoid cells, they are unlike any normal cells of that lineage. Moreover, the limited proliferative potential of HRS cells belies the clinical aggressiveness of Hodgkin lymphoma (HL). More than 20 years ago, the L428 HL cell line was reported to contain a small population of phenotypic B cells that appeared responsible for the continued generation of HRS cells. This observation, however, has never been corroborated, and such clonotypic B cells have never been documented in HL patients. We found that both the L428 and KM-H2 HL cell lines contained rare B-cell subpopulations responsible for the generation and maintenance of the predominant HRS cell population. The B cells within the HL cell lines expressed immunoglobulin light chain, the memory B-cell antigen CD27, and the stem cell marker aldehyde dehydrogenase (ALDH). Clonal CD27(+)ALDH(high) B cells, sharing immunoglobulin gene rearrangements with lymph node HRS cells, were also detected in the blood of most newly diagnosed HL patients regardless of stage. Although the clinical significance of circulating clonotypic B cells in HL remains unclear, these data suggest they may be the initiating cells for HL.

The fatty acid synthesis type II pathway has received considerable interest as a candidate therapeutic target in Plasmodium falciparum asexual blood-stage infections. This apicoplast-resident pathway, distinct from the mammalian type I process, includes FabI. Here, we report synthetic chemistry and transfection studies concluding that Plasmodium FabI is not the target of the antimalarial activity of triclosan, an inhibitor of bacterial FabI. Disruption of fabI in P. falciparum or the rodent parasite P. berghei does not impede blood-stage growth. In contrast, mosquito-derived, FabI-deficient P. berghei sporozoites are markedly less infective for mice and typically fail to complete liver-stage development in vitro. This defect is characterized by an inability to form intrahepatic merosomes that normally initiate blood-stage infections. These data illuminate key differences between liver- and blood-stage parasites in their requirements for host versus de novo synthesized fatty acids, and create new prospects for stage-specific antimalarial interventions.