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Most African countries have recorded relatively lower COVID-19 burdens than Western countries. This has been attributed to early and strong political commitment and robust implementation of public health measures, such as nationwide lockdowns, travel restrictions, face mask wearing, testing, contact tracing, and isolation, along with community education and engagement. Other factors include the younger population age strata and hypothesized but yet-to-be confirmed partially protective cross-immunity from parasitic diseases and/or other circulating coronaviruses. However, the true burden may also be underestimated due to operational and resource issues for COVID-19 case identification and reporting. In this perspective article, we discuss selected best practices and challenges with COVID-19 contact tracing in Nigeria, Rwanda, South Africa, and Uganda. Best practices from these country case studies include sustained, multi-platform public communications; leveraging of technology innovations; applied public health expertise; deployment of community health workers; and robust community engagement. Challenges include an overwhelming workload of contact tracing and case detection for healthcare workers, misinformation and stigma, and poorly sustained adherence to isolation and quarantine. Important lessons learned include the need for decentralization of contact tracing to the lowest geographic levels of surveillance, rigorous use of data and technology to improve decision-making, and sustainment of both community sensitization and political commitment. Further research is needed to understand the role and importance of contact tracing in controlling community transmission dynamics in African countries, including among children. Also, implementation science will be critically needed to evaluate innovative, accessible, and cost-effective digital solutions to accommodate the contact tracing workload.

Globally, there are prevailing knowledge gaps in the epidemiology, clinical manifestations, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among children and adolescents; and these gaps are especially wide in African countries. The availability of robust age-disaggregated data is a critical first step in improving knowledge on disease burden and manifestations of coronavirus disease 2019 (COVID-19) among children. Furthermore, it is essential to improve understanding of SARS-CoV-2 interactions with comorbidities and coinfections such as human immunodeficiency virus (HIV), tuberculosis, malaria, sickle cell disease, and malnutrition, which are highly prevalent among children in sub-Saharan Africa. The African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents is conducting studies across Western, Central, Eastern, and Southern Africa to address existing knowledge gaps. This consortium is expected to generate key evidence to inform clinical practice and public health policy-making for COVID-19 while concurrently addressing other major diseases affecting children in African countries.

The efficacy and safety of hydroxychloroquine (HCQ) for the prevention and treatment of COVID-19 has received great attention, and most notably, the enthusiasm for HCQ has been one of politicization rather than science. Laboratory studies and case series published early in the pandemic supported its efficacy. The scientific community raced to conduct observational and randomized evaluations of the drug in all stages of the disease, including prophylaxis, early treatment, and advanced disease. Yet a divisive media response affected recruitment, funding, and subsequent enthusiasm for continuing scientific investigations. Of the more than 300 HCQ trials registered, fewer than 50% report having recruited any patients, and most trials might fail to achieve any useful portions of their intended sample size. Multiple observational studies and two large randomized trials have demonstrated HCQ does not offer efficacy against COVID-19 in hospitalized patients. Prophylaxis studies and early treatment studies provided heterogeneous results and are plagued by low event rates and poor study outcome monitoring. Emerging high-quality evaluations of prophylaxis and early treatment do not support a role for HCQ in these populations. The story of HCQ for COVID-19 has followed a pattern of initial enthusiasm supported by poor quality evidence, followed by disappointment based on more rigorous evaluations. The experience of HCQ in the COVID-19 era calls for the depoliticization of science away from media glare.

This paper shows the scale of global health research and the context in which we frame the subsequent papers in the Series. In this Series paper, we provide a historical perspective on clinical trial research by revisiting the 1948 streptomycin trial for pulmonary tuberculosis, which was the first documented randomised clinical trial in the English language, and we discuss its close connection with global health. We describe the current state of clinical trial research globally by providing an overview of clinical trials that have been registered in the WHO International Clinical Trial Registry since 2010. We discuss challenges with current trial planning and designs that are often used in clinical trial research undertaken in low-income and middle-income countries, as an overview of the global health trials landscape. Finally, we discuss the importance of collaborative work in global health research towards generating sustainable and culturally appropriate research environments.

Little is known about the clinical features and outcomes of SARS-CoV-2 infection in Africa. We conducted a retrospective cohort study of patients hospitalized for COVID-19 between March 10, 2020 and July 31, 2020 at seven hospitals in Kinshasa, Democratic Republic of the Congo (DRC). Outcomes included clinical improvement within 30 days (primary) and in-hospital mortality (secondary). Of 766 confirmed COVID-19 cases, 500 (65.6%) were male, with a median (interquartile range [IQR]) age of 46 (34–58) years. One hundred ninety-one (25%) patients had severe/critical disease requiring admission in the intensive care unit (ICU). Six hundred twenty patients (80.9%) improved and were discharged within 30 days of admission. Overall in-hospital mortality was 13.2% (95% CI: 10.9–15.8), and almost 50% among those in the ICU. Independent risk factors for death were age < 20 years (adjusted hazard ratio [aHR] = 6.62, 95% CI: 1.85–23.64), 40–59 years (aHR = 4.45, 95% CI: 1.83–10.79), and ≥ 60 years (aHR = 13.63, 95% CI: 5.70–32.60) compared with those aged 20–39 years, with obesity (aHR = 2.30, 95% CI: 1.24–4.27), and with chronic kidney disease (aHR = 5.33, 95% CI: 1.85–15.35). In marginal structural model analysis, there was no statistically significant difference in odds of clinical improvement (adjusted odds ratio [aOR] = 1.53, 95% CI: 0.88–2.67, P = 0.132) nor risk of death (aOR = 0.65, 95% CI: 0.35–1.20) when comparing the use of chloroquine/azithromycin versus other treatments. In this DRC study, the high mortality among patients aged < 20 years and with severe/critical disease is of great concern, and requires further research for confirmation and targeted interventions.

The world is currently facing a novel COVID-19 pandemic caused by SARS-CoV-2 that, as of July 12, 2020, has caused a reported 12,322,395 cases and 556,335 deaths. To date, only two treatments, remdesivir and dexamethasone, have demonstrated clinical efficacy through randomized controlled trials (RCTs) in seriously ill patients. The search for new or repurposed drugs for treatment of COVID-19 continues. We have witnessed anecdotal use of herbal medicines, including Artemisia spp. extracts, in low-income countries, and exaggerated claims of their efficacies that are not evidence based, with subsequent political controversy. These events highlight the urgent need for further research on herbal compounds to evaluate efficacy through RCTs, and, when efficacious compounds are identified, to establish the active ingredients, develop formulations and dosing, and define pharmacokinetics, toxicology, and safety to enable drug development. Derivatives from the herb Artemisia annua have been used as traditional medicine over centuries for the treatment of fevers, malaria, and respiratory tract infections. We review the bioactive compounds, pharmacological and immunological effects, and traditional uses for Artemisia spp. derivatives, and discuss the challenges and controversies surrounding current efforts and the scientific road map to advance them to prevent or treat COVID-19.

As of June 11, 2020, the Democratic Republic of the Congo (DRC) has reported 4,258 COVID-19 cases with 90 deaths. With other African countries, the DRC faces the challenge of striking a balance between easing public health lockdown measures to curtail the spread of SARS-CoV-2 and minimizing both economic hardships for large sectors of the population and negative impacts on health services for other infectious and noninfectious diseases. The DRC recently controlled its tenth Ebola virus disease (EVD) outbreak, but COVID-19 and a new EVD outbreak beginning on June 1, 2020 in the northwest Équateur Province have added an additional burden to health services. Although the epidemiology and transmission of EVD and COVID-19 differ, leveraging the public health infrastructures and experiences from coordinating the EVD response to guide the public health response to COVID-19 is critical. Building on the DRC’s 40 years of experience with 10 previous EVD outbreaks, we highlight the DRC’s multi-sectoral public health approach to COVID-19, which includes community-based screening, testing, contact-tracing, risk communication, community engagement, and case management. We also highlight remaining challenges and discuss the way forward for achieving control of both COVID-19 and EVD in the DRC.

CITATION: Petersen, E. et al. 2020. COVID-19 travel restrictions and the International Health Regulations : call for an open debate on easing of travel restrictions. International Journal of Infectious Diseases, 94:88–90, doi:10.1016/j.ijid.2020.04.029.

Biomarkers for detecting early HIV infection and estimating HIV incidence should minimize false-recent rates (FRRs) while maximizing mean duration of recent infection (MDRI). We compared HIV subtypes B, E and D (BED) capture enzyme immunoassay (BED), Sedia limiting antigen (LAg) avidity enzyme immunoassay, and Bio-Rad avidity incidence (BRAI) assays using samples from Zimbabwean postpartum women infected with clade C HIV. We calculated MDRIs using 590 samples from 351 seroconverting postpartum women, and FRRs using samples from 2,825 women known to be HIV positive for >12 months. Antibody kinetics were more predictable with LAg and had higher precision compared with BED or BRAI. BRAI also exhibited more variability, and avidity reversal in some cases. For BED, LAg, and BRAI, used alone or with viral load, MDRI values in days were: BED-188 and 170 at normalized optical density (ODn) 0.8; LAg-104 and 100 at ODn cutoff 1.5; BRAI-135 and 134 at avidity index cutoff 30%. Corresponding FRRs were: BRAI 1.1% and 1.0% and LAg 0.57% and 0.35%: these were 3.8-10.9 times lower than BED values of 4.8% and 3.8%. BRAI and LAg have significantly lower FRRs and MDRIs than in published studies, and much lower than BED and could be used to estimate incidence in perinatal women and to measure population-level HIV incidence in HIV control operations in Africa.

Background Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. Methods of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan–Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death. Results Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63–3.59), retreatment of TB (aOR 4.92, 95% CI 2.31–10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01–3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3–60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2–6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88–9.71). Conclusions Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes., In tuberculosis (TB) patients from post-conflict eastern Democratic Republic of the Congo, 11.1% had rifampicin-resistant TB, of whom 46.5% had no prior TB. Cures were achieved in 83% and 74% of patients on 9- and 20/24-month multidrug-resistant TB regimens, respectively.

Background: Little is known about the prevalence of co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) in the post-conflict South-Kivu Province, Eastern Democratic Republic of the Congo. Therefore, we aimed to determine such data at Panzi Referral Hospital. Methods: We conducted a cross-sectional study of 198 HIV-positive patients seen in consultation from June to 31 November 2017. Socio-demographic and clinical data were collected by interview and clinical examination. Blood sample was taken for serological analyses. The presence of HBV serological markers was determined by enzyme linked immunoassay (ELISA) tests. CD4+ T cell counts were determined for all patients. Data analysis was done using the JMP 7.1 software. Proportions were compared using a Chi-square test or Fisher test. Results: Fourteen of 198 participants (7.07%, 95% confidence interval [CI]: 4.35 - 11.51) were HBsAg-positive. Overall, 33.33% of the subjects had been in contact with HBV and 36.87% were carriers of the immunization marker. Among co-infected patients, 28.57% had a chronic replicative viral B infection, 57.14% a chronic non-replicative infection and 14.29% were inactive carriers. No patient had an acute infection. Co-infection was higher in participants who were aged 55 and over (8.3%), men (12.90%, p = 0.0306), married (12.00%, p = 0.0063), or of Lega ethnicity (14.3%, p = 0.0100). Some clinical signs such as hepatomegaly and jaundice (p < 0.0001), fever (p = 0.0095), splenomegaly (p = 0.0007), ascites (p = 0.0173) and viral encephalitis (p ≤ 0.0001) were associated with co-infection. Severe immunosuppression (50.00%, p = 0.0110) and WHO clinical stage III/IV (10.64%; p = 0.0301) were associated with HIV/HBV co-infection. Conclusions: The relative high prevalence of HIV/HBV co-infection and chronic nature call for the need of integrating HBV screening programs into HIV routine care to reduce morbidity and mortality levels caused by HIV/HBV co-infection.

Introduction Addressing the intersection between mental health and HIV is critical for the wellbeing of persons living with HIV (PLWH). This systematic review synthesized the literature on mental health interventions for PLWH in low‐ and middle‐income countries (LMICs) to determine intervention components and explore their relationship with intervention effectiveness. Methods We included only controlled clinical trials of interventions aiming to improve the mental health of PLWH. We conducted a search in the following databases: PubMed, CINAHL, PsycINFO and EMBASE for eligible studies describing the evaluation of interventions for mental health problems among PLWH in LMICs published through August 2020. Two reviewers independently screened references in two successive stages of title/abstract screening and then full‐text screening for references meeting title/abstract criteria. Results We identified a total of 30 eligible articles representing 6477 PLWH who were assigned to either the intervention arm (n = 3182) or control arm (n = 3346). The mental health interventions evaluated were psychological (n = 17, 56.67%), pharmacological (n = 6, 20.00%), combined psychological and pharmacological (n = 1, 3.33%) and complementary/alternative treatments (n = 6, 20.00%). The mental health problems targeted were depression (n = 22, 73.33 %), multiple psychological symptoms (n = 1, 3.33%), alcohol and substance use problems (n = 4, 13.33%), post‐traumatic stress disorder (n = 1, 3.33%) and HIV‐related neuro‐cognitive impairment (n = 2, 6.67%). Studies of interventions with significant effects had significantly a higher number of active ingredients than those without significant effects [3.41 (2.24) vs. 1.84 (1.46) Mean (SD)] [Mean difference = −1.56, 95% CI = −3.03 to −0.09, p = 0.037]. Conclusions There continue to be advances in mental health interventions for PLWH with mental illness in LMICs. However, more research is needed to elucidate how intervention components lead to intervention effectiveness. We recommend scale up of culturally appropriate interventions that have been successfully evaluated in low‐ and middle‐income countries.

Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5-71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by − 0.85% (− 0.19 to − 0.52) (p ≤ 0.0001) and − 14% (− 28.22 to − 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05-1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome. Pulmonary tuberculosis (PTB) kills almost 2 million individuals every year and is thus a leading cause of death among adults worldwide. Mycobacterium tuberculosis (Mtb) infects more than 10 million people each year 1-3. Mtb potently induces cytokines and chemokines from polymorphonuclear cells and monocytes, thus resulting in intense local inflammation in the lungs 4. Alveolar macrophages are anti-inflammatory in nature, but their function can be impaired by pollutants, including mineral dusts, thereby diminishing the body's ability to clear infections 5-8. This is probably why mineworkers are more susceptible to develop PTB. Telomere length (TL) reflects the history of oxidative stress and chronic inflammation, and is a marker for age-related disease susceptibility 9-12. In normal physiology, mitochondria are important in the cell as they generate most of the adenosine triphosphate (ATP) through the oxidative phosphorylation mechanism (OXPHOS), which is a critical energy supply for cellular processes and partially encoded with mitochondrial DNA (mtDNA). The OXPHOS mechanism uses dietary intake to produce ATP, but it also produces ROS which can destroy mitochon-drial DNA, impairs respiratory chain function and cause nuclear DNA damage 12-14. Further, Mitochondrial DNA (mtDNA) damage can result in genomic instability, cellular senescence and altered intercellular communication. Hallmarks of aging genomic instability and deregulated nutrient sensing can contribute to reduced mitochondrial OPEN Funding P.D.M.C.K was fellow of the Fonds Marc Vervenne of the KU Leuven (Belgium) and he is supported by the US National Institutes of Health (NIH)-Fogarty Postdoctoral Fellowship: Grant no. 1D43TW010937-01A1. D.S.M is a FWO postdoc, with funding number: FWO Grant 12X9620N. Fieldwork has been supported by the KU Leuven Alumni Association and the University of Antwerp-USOS via the CEGEMI of the Catholic University of Bukavu. The costs of measuring Telomere length and mtDNA were covered by a grant of the European Research Council (ENVIRONAGE). The funders had no role in the study design, data collection, analysis, interpretation, or writing of the report. The corresponding author had full access to all the study data and had final responsibility for the decision to submit for publication. Acknowledgements We thank Profs J. Balmes (UCSF), N. Lorent, E. André (KU Leuven), and C. Tonne (ISGlobal) for their critical appraisal of the manuscript. We are grateful to the study participants and their relatives, the TB clinics, and the DRC’s National/Provincial TB and HIV programs for their collaboration.

Background Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)–detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). Methods We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. Results Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1–100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5–72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. Conclusions In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.

The novel severe acute respiratory syndrome-coronavirus-2 pandemic has spread to Africa, where nearly all countries have reported laboratory-confirmed cases of novel coronavirus disease (COVID-19). Although there are ongoing clinical trials of repurposed and investigational antiviral and immune-based therapies, there are as yet no scientifically proven, clinically effective pharmacological treatments for COVID-19. Among the repurposed drugs, the commonly used antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) have become the focus of global scientific, media, and political attention despite a lack of randomized clinical trials supporting their efficacy. Chloroquine has been used worldwide for about 75 years and is listed by the WHO as an essential medicine to treat malaria. Hydroxychloroquine is mainly used as a therapy for autoimmune diseases. However, the efficacy and safety of CQ/HCQ for the treatment of COVID-19 remains to be defined. Indiscriminate promotion and widespread use of CQ/HCQ have led to extensive shortages, self-treatment, and fatal overdoses. Shortages and increased market prices leave all countries vulnerable to substandard and falsified medical products, and safety issues are especially concerning for Africa because of its healthcare system limitations. Much needed in Africa is a cross-continental collaborative network for coordinated production, distribution, and post-marketing surveillance aligned to low-cost distribution of any approved COVID-19 drug; this would ideally be piggybacked on existing global aid efforts. Meanwhile, African countries should strongly consider implementing prescription monitoring schemes to ensure that any off-label CQ/HCQ use is appropriate and beneficial during this pandemic.

SETTING Tygerberg Hospital, Western Cape Province, Cape Town, South Africa. OBJECTIVE To investigate the prevalence of and factors associated with simultaneous tuberculosis (TB) and human immunodeficiency virus (HIV) diagnoses in children. DESIGN Retrospective cohort study in TB-HIV co-infected children aged

The HPTN 071 (PopART) trial showed that a combination HIV prevention package including universal HIV testing and treatment (UTT) reduced population-level incidence of HIV compared with standard care. However, evidence is scarce on the costs and cost-effectiveness of such an intervention.Using an individual-based model, we simulated the PopART intervention and standard care with antiretroviral therapy (ART) provided according to national guidelines for the 21 trial communities in Zambia and South Africa (for all individuals aged14 years), with model parameters and primary cost data collected during the PopART trial and from published sources. Two intervention scenarios were modelled: annual rounds of PopART from 2014 to 2030 (PopART 2014-30; as the UNAIDS Fast-Track target year) and three rounds of PopART throughout the trial intervention period (PopART 2014-17). For each country, we calculated incremental cost-effectiveness ratios (ICERs) as the cost per disability-adjusted life-year (DALY) and cost per HIV infection averted. Cost-effectiveness acceptability curves were used to indicate the probability of PopART being cost-effective compared with standard care at different thresholds of cost per DALY averted. We also assessed budget impact by projecting undiscounted costs of the intervention compared with standard care up to 2030.During 2014-17, the mean cost per person per year of delivering home-based HIV counselling and testing, linkage to care, promotion of ART adherence, and voluntary medical male circumcision via community HIV care providers for the simulated population was US$6·53 (SD 0·29) in Zambia and US$7·93 (0·16) in South Africa. In the PopART 2014-30 scenario, median ICERs for PopART delivered annually until 2030 were $2111 (95% credible interval [CrI] 1827-2462) per HIV infection averted in Zambia and $3248 (2472-3963) per HIV infection averted in South Africa; and $593 (95% CrI 526-674) per DALY averted in Zambia and $645 (538-757) per DALY averted in South Africa. In the PopART 2014-17 scenario, PopART averted one infection at a cost of $1318 (1098-1591) in Zambia and $2236 (1601-2916) in South Africa, and averted one DALY at $258 (225-298) in Zambia and $326 (266-391) in South Africa, when outcomes were projected until 2030. The intervention had almost 100% probability of being cost-effective at thresholds greater than $700 per DALY averted in Zambia, and greater than $800 per DALY averted in South Africa, in the PopART 2014-30 scenario. Incremental programme costs for annual rounds until 2030 were $46·12 million (for a mean of 341 323 people) in Zambia and $30·24 million (for a mean of 165 852 people) in South Africa.Combination prevention with universal home-based testing can be delivered at low annual cost per person but accumulates to a considerable amount when scaled for a growing population. Combination prevention including UTT is cost-effective at thresholds greater than $800 per DALY averted and can be an efficient strategy to reduce HIV incidence in high-prevalence settings.US National Institutes of Health, President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, BillMelinda Gates Foundation.

Little is known about the major cardiovascular risk factors in HIV-infected as compared to the HIV-uninfected patients in the Democratic Republic of Congo (DR Congo). We determined the prevalence of hypertension, obesity (BMI ≥ 30 kg/m2), total cholesterol > 200 mg/dl, HDLcholesterol &≤ 40 mg/dl, and glycemia > 126 mg/dl. We also calculated the average and/or median of total cholesterol, HDL-cholesterol, and glycemia among HIV-infected and HIV-uninfected patients.We conducted a cross-sectional study that enrolled 592 HIV-uninfected and 445 HIV-infected patients of whom 425 (95.5%) were on first-line antiretroviral therapy based on stavudine-lamivudine-nevirapine. Clinical and laboratory data of the patients were collected. The results were analyzed by chi-square, t-student, and Wilcoxon rank sum tests. 11.5% of HIV-infected patients had an average blood pressure suggesting hypertension versus 10.6% of HIV-uninfected (P = 0.751). But in absolute value, HIVinfected patients had a median of diastolic blood pressure of 90 mmHg versus 85 mmHg of HIV-uninfected (P 200 mg/dl and HDL-cholesterol ≤ 40 mg/dl. Proactive screening and prompt management of dyslipidemia and hypertension in this population should be a priority.

Summary Background Although lifelong combination antiretroviral therapy (ART) is recommended for all individuals with HIV, few data exist for pregnancy outcomes associated with ART initiation before conception. We assessed adverse pregnancy outcomes associated with ART initiated before conception compared with that of ART started after conception. Methods We did a systematic review of studies from low-income, middle-income, and high-income countries by searching the Cochrane Central Register of Controlled Trials, Embase, LILACS, MEDLINE, Toxline, Web of Knowledge, and WHO Global Index Medicus and trials in progress (International Clinical Trials Registry Platform) for randomised trials, quasi-randomised trials, and prospective cohort studies done between Jan 1, 1980, and June 1, 2016, in which timing of ART initiation in pregnant women living with HIV was reported. We used the risk ratio (RR) and corresponding 95% CIs as the primary measure to assess the association between the selected outcomes and ART initiation before conception versus after conception. We used a random-effects model to pool risk ratios. Findings We included 11 studies with 19 189 mother–infant pairs. Women who started ART before conception were significantly more likely to deliver preterm (pooled RR 1·20, 95% CI 1·01−1·44) or very preterm (1·53, 1·22−1·92), or to have low-birthweight infants (1·30, 1·04−1·62) than were those who began ART after conception. Few data exist for neonatal mortality. The risk of very low birthweight, small for gestational age, severe small for gestational age, stillbirth, and congenital anomalies did not differ significantly between women who were taking ART before conception and those who began ART after conception. Interpretation The benefits of ART for maternal health and prevention of perinatal transmission outweigh risks, but data for the extent and severity of these risks are scarce and of low quality. As use of ART before conception rapidly increases globally, monitoring for potential adverse pregnancy outcomes will be crucial. Funding WHO.

Background Despite antiretroviral therapy (ART) being widely available, HIV continues to cause substantial illness and premature death in low‐and‐middle‐income countries. High rates of loss to follow‐up after HIV diagnosis can delay people starting ART. Starting ART within seven days of HIV diagnosis (rapid ART initiation) could reduce loss to follow‐up, improve virological suppression rates, and reduce mortality. Objectives To assess the effects of interventions for rapid initiation of ART (defined as offering ART within seven days of HIV diagnosis) on treatment outcomes and mortality in people living with HIV. We also aimed to describe the characteristics of rapid ART interventions used in the included studies. Search methods We searched CENTRAL, the Cochrane Database of Systematic Reviews, MEDLINE, Embase, and four other databases up to 14 August 2018. There was no restriction on date, language, or publication status. We also searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, and websites for unpublished literature, including conference abstracts. Selection criteria We included randomized controlled trials (RCTs) that compared rapid ART versus standard care in people living with HIV. Children, adults, and adolescents from any setting were eligible for inclusion. Data collection and analysis Two review authors independently assessed the eligibility of the studies identified in the search, assessed the risk of bias and extracted data. The primary outcomes were mortality and virological suppression at 12 months. We have presented all outcomes using risk ratios (RR), with 95% confidence intervals (CIs). Where appropriate, we pooled the results in meta‐analysis. We assessed the certainty of the evidence using the GRADE approach. Main results We included seven studies with 18,011 participants in the review. All studies were carried out in low‐ and middle‐income countries in adults aged 18 years old or older. Only one study included pregnant women. In all the studies, the rapid ART intervention was offered as part of a package that included several cointerventions targeting individuals, health workers and health system processes delivered alongside rapid ART that aimed to facilitate uptake and adherence to ART. Comparing rapid ART with standard initiation probably results in greater viral suppression at 12 months (RR 1.18, 95% CI 1.10 to 1.27; 2719 participants, 4 studies; moderate‐certainty evidence) and better ART uptake at 12 months (RR 1.09, 95% CI 1.06 to 1.12; 3713 participants, 4 studies; moderate‐certainty evidence), and may improve retention in care at 12 months (RR 1.22, 95% CI 1.11 to 1.35; 5001 participants, 6 studies; low‐certainty evidence). Rapid ART initiation was associated with a lower mortality estimate, however the CIs included no effect when compared to standard of care (RR 0.72, 95% CI 0.51 to 1.01; 5451 participants, 7 studies; very low‐certainty evidence). It is uncertain whether rapid ART has an effect on modification of ART treatment regimens as data are lacking (RR 7.89, 95% CI 0.76 to 81.74; 977 participants, 2 studies; very low‐certainty evidence). There was insufficient evidence to draw conclusions on the occurrence of adverse events. Authors' conclusions RCTs that include initiation of ART within one week of diagnosis appear to improve outcomes across the HIV treatment cascade in low‐ and middle‐income settings. The studies demonstrating these effects delivered rapid ART combined with several setting‐specific cointerventions. This highlights the need for pragmatic research to identify feasible packages that assure the effects seen in the trials when delivered through complex health systems. 16 September 2019 Up to date All studies incorporated from most recent search All published trials found in the last search (14 Aug, 2018) were included, and we identified three ongoing studies, Plain language summary Effects of starting antiretroviral therapy within one week of diagnosis on people living with HIV What is the aim of this review? The aim was to determine whether starting antiretroviral therapy (ART) within one week of HIV diagnosis (rapid ART) resulted in a lower risk of dying or better suppression of the virus in people's blood than standard care; as well as studying the effect of this intervention on whether people start taking ART and continue to be engaged in care after 12 months. Key messages Offering ART to people living with HIV (PLWH) within one week of diagnosis probably increases the number of people initiating the therapy at 12 months and the number of PLWH whose virus has been suppressed in the blood at 12 months. It may also improve the number of people who are still in contact with healthcare services at 12 months. We don't know the effect this has on people dying. We found that several other changes need to be made alongside rapid ART for services to achieve these outcomes. What was studied in the review? HIV is a leading cause of death worldwide. Although more people are taking ART than ever before, there is a large percentage of PLWH who are not being treated. One of the reasons identified is the long period between being diagnosed with HIV and starting ART. Rapid ART has been proposed as a way to increase the number of PLWH being started on ART and improve HIV‐related outcomes. What are the main results of the review? We found seven studies that met the inclusion criteria of the review and assessed the effect of rapid ART on PLWH. Rapid ART probably increases the number of people being initiated on ART at 12 months and the number of PLWH with no detectable virus in their blood at 12 months (moderate‐certainty evidence). Based on low‐certainty evidence, rapid ART may increase the number of PLWH being retained in care. We don't know whether rapid ART has an effect on the number of deaths (very low‐certainty evidence). We found that if healthcare services aim to offer ART within a week of diagnosis, changes to how these systems operate will need to be made. How up to date is the review? We searched for relevant trials up to 14 August 2018.

Little is known about the effect of community versus health facility-based interventions to improve and sustain antiretroviral therapy (ART) adherence, virologic suppression, and retention in care among HIV-infected individuals in low- and middle-income countries (LMICs). We systematically searched four electronic databases for all available randomized controlled trials (RCTs) and comparative cohort studies in LMICs comparing community versus health facility-based interventions. Relative risks (RRs) for pre-defined adherence, treatment engagement (linkage and retention in care), and relevant clinical outcomes were pooled using random effect models. Eleven cohort studies and eleven RCTs (N = 97,657) were included. Meta-analysis of the included RCTs comparing community- versus health facility-based interventions found comparable outcomes in terms of ART adherence (RR = 1.02, 95 % CI 0.99 to 1.04), virologic suppression (RR = 1.00, 95 % CI 0.98 to 1.03), and all-cause mortality (RR = 0.93, 95 % CI 0.73 to 1.18). The result of pooled analysis from the RCTs (RR = 1.03, 95 % CI 1.01 to 1.06) and cohort studies (RR = 1.09, 95 % CI 1.03 to 1.15) found that participants assigned to community-based interventions had statistically significantly higher rates of treatment engagement. Two studies found community-based ART delivery model either cost-saving or cost-effective. Community- versus facility-based models of ART delivery resulted in at least comparable outcomes for clinically stable HIV-infected patients on treatment in LMICs and are likely to be cost-effective.

As access to antiretroviral treatment in low- and middle-income countries improves, the number of older adults (aged ≥ 50 years) living with HIV is increasing. This study compares the adherence to antiretroviral treatment among older adults to that of younger adults living in Africa. We searched PubMed, Medline, Cochrane CENTRAL, CINAHL, Google Scholar and EMBASE for keywords (HIV, ART, compliance, adherence, age, Africa) on publications from 1st Jan 2000 to 1st March 2016. Eligible studies were pooled for meta-analysis using a random-effects model, with the odds ratio as the primary outcome. Twenty studies were included, among them were five randomised trials and five cohort studies. Overall, we pooled data for 148,819 individuals in two groups (older and younger adults) and found no significant difference in adherence between them [odds ratio (OR) 1.01; 95% CI 0.94–1.09]. Subgroup analyses of studies using medication possession ratio and clinician counts to measure adherence revealed higher proportions of older adults were adherent to medication regimens compared with younger adults (OR 1.06; 95% CI 1.02–1.11). Antiretroviral treatment adherence levels among older and younger adults in Africa are comparable. Further research is required to identify specific barriers to adherence in the aging HIV affected population in Africa which will help in development of interventions to improve their clinical outcomes and quality of life.

OBJECTIVE: To determine the prevalence of and risk factors for metabolic syndrome (MS) in HIV-infected adults at three urban clinics in Bukavu, Democratic Republic of the Congo. DESIGN: Cross-sectional study. METHODS: From July to September 2016, baseline socio-demographics, risk factors and clinical characteristics were collected using a structured questionnaire or extracted from medical records. Fasting blood sugar and lipids were measured. MS was defined per the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) and the International Diabetes Federation (IDF) criteria. Adjusted odds ratio (OR) was generated through multivariate logistic regression models. RESULTS: Of 495 participants, 356 (72%) were women and 474 (95.8%) were receiving antiretroviral therapy (ART). The median age (years) [interquartile range (IQR)] was 43 [36-51]. The overall prevalence of MS per NECP/ATP III and IDF criteria was 27% [95% CI: 20-35%] or 30% [95% CI: 23-38%], respectively. In a multivariate logistic regression, low physical activity (OR 2.47, 95% CI: 1.40-4.36); daily exposure to biomass fuel smoke (BMF) for more than 2 h (OR 2.18, 95% CI: 1.01-4.68); protease inhibitor containing ART (OR: 2.96, 95% CI: 1.07-8.18); and stavudine-containing ART regimen (OR: 2.57, 95% CI: 1.11-5.93) were independently associated with MS. CONCLUSIONS: MS was highly prevalent in this hospital-based study population. Beside known traditional risk factors and contribution of specific ART regimens to MS, daily exposure to BMF is new and of specific concern, necessitating targeted urgent prevention and management interventions.

Little is known about the respiratory health damage related to household air pollution (HAP) in survivors of pulmonary tuberculosis (PTB). In a population-based cross-sectional study, we determined the prevalence and associated predictors of chronic cough and hemoptysis in 441 randomly selected PTB survivors living in 13 remote health zones with high TB burden in the South Kivu province of the Democratic Republic of Congo (DRC). Trained community and health-care workers administered a validated questionnaire. In a multivariate logistic regression, chronic cough was independently associated with HAP (adjusted odds ratios (aOR) 2.10, 95% CI: 1.10&ndash, 4.00) and PTB treatment &gt, 6 months (aOR 3.80, 95% CI: 1.62&ndash, 8.96). Among women, chronic cough was associated with cooking &ge, 3 h daily (aOR 2.74, 95% CI: 1.25&ndash, 6.07) and with HAP (aOR 3.93, 95% CI: 1.15&ndash, 13.43). Independent predictors of hemoptysis were PTB retreatment (aOR 3.04, 95% CI: 1.04&ndash, 5.09) and ignorance of treatment outcome (aOR 2.24, 95% CI: 1.09&ndash, 4.58) but not HAP (aOR 1.86, 95% CI: 0.61&ndash, 5.62). Exposure to HAP proved a major risk factor for chronic cough in PTB survivors, especially in women. This factor is amenable to intervention.

Introduction Several studies have measured health outcomes in the United States, but none have provided a comprehensive assessment of patterns of health by state. Objective To use the results of the Global Burden of Disease Study (GBD) to report trends in the burden of diseases, injuries, and risk factors at the state level from 1990 to 2016. Design and Setting A systematic analysis of published studies and available data sources estimates the burden of disease by age, sex, geography, and year. Main Outcomes and Measures Prevalence, incidence, mortality, life expectancy, healthy life expectancy (HALE), years of life lost (YLLs) due to premature mortality, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 333 causes and 84 risk factors with 95% uncertainty intervals (UIs) were computed. Results Between 1990 and 2016, overall death rates in the United States declined from 745.2 (95%UI, 740.6 to 749.8) per 100 000 persons to 578.0 (95%UI, 569.4 to 587.1) per 100 000 persons. The probability of death among adults aged 20 to 55 years declined in 31 states and Washington, DC from 1990 to 2016. In 2016, Hawaii had the highest life expectancy at birth (81.3 years) and Mississippi had the lowest (74.7 years), a 6.6-year difference. Minnesota had the highest HALE at birth (70.3 years), andWest Virginia had the lowest (63.8 years), a 6.5-year difference. The leading causes of DALYs in the United States for 1990 and 2016 were ischemic heart disease and lung cancer, while the third leading cause in 1990 was low back pain, and the third leading cause in 2016 was chronic obstructive pulmonary disease. Opioid use disorders moved from the 11th leading cause of DALYs in 1990 to the 7th leading cause in 2016, representing a 74.5%(95%UI, 42.8%to 93.9%) change. In 2016, each of the following 6 risks individually accounted for more than 5%of risk-attributable DALYs: tobacco consumption, high body mass index (BMI), poor diet, alcohol and drug use, high fasting plasma glucose, and high blood pressure. Across all US states, the top risk factors in terms of attributable DALYs were due to 1 of the 3 following causes: tobacco consumption (32 states), high BMI (10 states), or alcohol and drug use (8 states). Conclusions and Relevance There are wide differences in the burden of disease at the state level. Specific diseases and risk factors, such as drug use disorders, high BMI, poor diet, high fasting plasma glucose level, and alcohol use disorders are increasing and warrant increased attention. These data can be used to inform national health priorities for research, clinical care, and policy.

Background: Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment remains challenging. Purpose: To assess evidence from randomized, controlled trials of the timing of ART initiation in HIV-infected adults with newly diagnosed pulmonary TB. Data Sources: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, conference abstracts, and ClinicalTrials.gov (from January 1980 to May 2015). Study Selection: Randomized, controlled trials evaluating early versus delayed ART initiation (1 to 4 weeks vs. 8 to 12 weeks after initiation of TB treatment) or deferred ART initiation (after the end of TB treatment). Data Extraction: Three reviewers independently extracted data and assessed risk of bias. The main outcome measures were all-cause mortality and the TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Data Synthesis: The 8 included trials (n = 4568) were conducted in Africa, Asia, and the United States and were generally at low risk of bias for the assessed domains. Overall, early ART reduced mortality compared with delayed ART (relative risk [RR], 0.81 [95% CI, 0.66 to 0.99]; I2 = 0%). In a prespecified subgroup analysis, early ART reduced mortality compared with delayed ART among patients with baseline CD4+ T-cell counts less than 0.050 × 109 cells/L (RR, 0.71 [CI, 0.54 to 0.93]; I2 = 0%). However, a mortality benefit from early ART was not found among those with CD4+ T-cell counts greater than 0.050 × 109 cells/L (RR, 1.05 [CI, 0.68 to 1.61]; I2 = 56%). Early ART was associated with a higher incidence of TB-IRIS than delayed ART (RR, 2.31 [CI, 1.87 to 2.86]; I2 = 19%). Limitation: Few trials provided sufficient data for subgroup analysis. Conclusion: Early ART in HIV-infected adults with newly diagnosed TB improves survival in those with CD4+ T-cell counts less than 0.050 × 109 cells/L, although this is associated with a 2-fold higher frequency of TB-IRIS. In patients with CD4+ T-cell counts greater than 0.050 × 109 cells/L, evidence is insufficient to support or refute a survival benefit conferred by early versus delayed ART initiation.

BACKGROUND Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. METHODS We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level

Summary Background Adherence to antiretroviral therapy (ART) is necessary for the improvement of the health of patients and for public health. We sought to determine the comparative effectiveness of different interventions for improving ART adherence in HIV-infected people living in Africa. Methods We searched for randomised trials of interventions to promote antiretroviral adherence within adults in Africa. We searched AMED, CINAHL, Embase, Medline (via PubMed), and ClinicalTrials.gov from inception to Oct 31, 2014, with the terms "HIV", "ART", "adherence", and "Africa". We created a network of the interventions by pooling the published and individual patients' data for comparable treatments and comparing them across the individual interventions with Bayesian network meta-analyses. The primary outcome was adherence defined as the proportion of patients meeting trial defined criteria; the secondary endpoint was viral suppression. Findings We obtained data for 14 randomised controlled trials, with 7110 patients. Interventions included daily and weekly short message service (SMS; text message) messaging, calendars, peer supporters, alarms, counselling, and basic and enhanced standard of care (SOC). Compared with SOC, we found distinguishable improvement in self-reported adherence with enhanced SOC (odds ratio [OR] 1·46, 95% credibility interval [CrI] 1·06–1·98), weekly SMS messages (1·65, 1·25–2·18), counselling and SMS combined (2·07, 1·22–3·53), and treatment supporters (1·83, 1·36–2·45). We found no compelling evidence for the remaining interventions. Results were similar when using viral suppression as an outcome, although the network contained less evidence than that for adherence. Treatment supporters with enhanced SOC (1·46, 1·09–1·97) and weekly SMS messages (1·55, 1·01–2·38) were significantly better than basic SOC. Interpretation Several recommendations for improving adherence are unsupported by the available evidence. These findings can inform future intervention choices for improving ART adherence in low-income settings. Funding None.

Objective To determine the prevalence and factors associated with optimal antiretroviral therapy (ART) adherence and virological failure (VLF) among HIV-infected adults enrolled in the national ART programme at the teaching hospital of Fann, Dakar, Senegal. Methods Cross-sectional study from 1 September 2013 to 30 January 2014. Outcomes: (1) optimal ART adherence by the Center for Adherence Support Evaluation (CASE) Index Score (>10) and (2) VLF (HIV RNA > 1000 copies/ml). Diagnostic accuracy of CASE Index Score assessed using sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and corresponding 95% confidence intervals (CIs). Multivariate logistic regression analysis was performed to identify independent factors associated with optimal adherence and VLF. Results Of 98 HIV-infected patients on ART, 68% were female. The median (IQR) age was 42 (20–50) years. A total of 57 of 98 (60%) were on ART more than 3 years, and majority (88%) were on NNRTI-based first-line ART regimen. A total of 79 of 98 (80%) patients reported optimal ART adherence, and only five of 84 (5.9%) had documented VLF. Patients with VLF were significantly more likely to have suboptimal ART adherence (17.7% vs. 2.9%; P = 0.02). CASE Index Score showed the best trade-off in Se (78.9%, 95% CI: 54.4–93.9%), Sp (20.0%, 95% CI: 11.1–31.7), PPV (22.4, 95% CI: 13.1–34.2%) and NPV (76.5%, 95% CI: 50.1–93.2), when used VLF threshold of HIV RNA >50 copies/ml. Factors independently associated with VLF were CASE Index Score

Background: Suboptimal adherence to antiretroviral therapy (ART) is a strong predictor of virologic failure (VF) among people with HIV. Various methods such as patient self-report, pill counts and pharmacy refills have been utilized to monitor adherence. However, there are limited data on the accuracy of combining methods to better predict VF in routine clinical settings. We examined various methods to assess adherence including pill count, medication possession ratio (MPR), and self-reported adherence in order to determine which was most highly associated with VF after > 6 months on ART. Methods: We conducted a secondary analysis of data from a case-control study. At enrollment, pharmacy refill data were collected retrospectively from the medical chart, pill counts were completed to derive a pill count adherence ratio (PCAR) and a self-report questionnaire was administered to all participants. Parametric smooth splines and receiver operator characteristic (ROC) analyses were carried out to assess the accuracy of the adherence methods. Results: 458 patients were enrolled from October 2010 to June 2012. Of these, 158 (34.50%) experienced VF (cases) and 300 (65.50%) were controls. The median (IQR) PCAR was 1.10 (0.99-1.14) for cases and 1.13 (1.08-1.18) for controls (p

Africa's health care challenges include a high burden of disease, low life expectancy, health workforce shortages, and varying degrees of commitment to primary health care on the part of policy makers and government officials. One overarching goal of the Medical Education Partnership Initiative (MEPI) is to develop models of medical education in Sub-Saharan Africa. To do this, MEPI has created a network of universities and other institutions that, among other things, recognizes the importance of supporting training programs in family medicine. This article provides a framework for assessing the stage of the development of family medicine training in Africa, including the challenges that were encountered and how educational organizations can help to address them. A modified "stages of change" model (precontemplation, contemplation, action, maintenance, and relapse) was used as a conceptual framework to understand the various phases that countries go through in developing family medicine in the public sector and to determine the type of assistance that is useful at each phase.

Design: Few global studies have assessed HIV clinician–patient communication regarding cardiovascular disease (CVD) risks. Methods: We conducted a multicountry, comparative, cross-sectional survey of HIV-infected individuals in 12 countries on 5 continents in 2010, with 100 to 200 enrollees per country. HIV-infected adults >17 years and on antiretroviral therapy were recruited in clinics and community organizations and surveyed via direct interview, telephone encounter, or online. Chi-square analyses were performed with an 80% power to detect a difference of >20%. Results: Of 2035 participants, 37% were women. Prevalence of self-reported CVD risk factors was 28% overall, and greater CVD risk was present in 55% of patients in North America, 12% in Africa, and 26% to 28% on other continents. Only 19% of patients ever discussed CVD with their physician, and 31% had ever discussed hypertension, hypercholesterolemia, family history of CVD, or smoking; these findings were true for HIV clinicians in all regions of the world. Forty-four percent of smokers reported never discussing smoking with their HIV clinician. Conclusion: We found that HIV clinicians worldwide are not sufficiently addressing CVD risk factors with their patients. Expanded training and education for HIV clinicians should include effective approaches to the mitigation of CV risk factors.

Although malaria remains one of the most important infectious causes of morbidity and mortality world-wide with 40% of the global population at risk, significant progress has been made toward elimination, notably with the development and use of rapid diagnostic tests, insecticide-treated bed nets, indoor residual spraying, and artemisinin-based combination therapies (ACTs). P. falciparum infection remains the most common cause of severe infection and death, but non-P. P. falciparum infections, including the recently emerged 5(th) plasmodium species, P. knowlesi, are increasingly recognized as causes of severe disease, especially in southeast Asia. Chemotherapy for severe infections has been revolutionized following results of the SEQUAMAT and AQUAMAT trials showing that parenteral artesunate (versus quinine) reduced severe malaria mortality by 34.7% and 22.5% in Asian adults and African children, respectively, making it the drug of choice for severe malaria. However, rising rates of artemisinin resistance, currently confined to the Greater Mekong sub-region, are threatening the long-term efficacy of artemisinins. HIV infection remains an important risk factor for death and severe disease due to malaria. The full amplitude of mutual interactions between these conditions is only beginning to be elucidated while the complex, multi-directional and pharmacokinetic interactions between antimalarial agents and HIV drugs continue to emerge.

Recent data from studies on treatment as prevention (TasP) and preexposure prophylaxis (PrEP) show that antiretroviral drugs can be used in prevention, as well as in treatment. The movement from first-generation antiretroviral therapy (ART) coformulations based on thymidine analogues to second-generation ART coformulations based on tenofovir may coincide with future prevention strategies that also use tenofovir/emtricitabine, raising concerns regarding drug resistance. In published studies, failure of prophylaxis was associated with poor adherence and low plasma drug levels. Although rates of drug resistance in cases of failed prevention was low, regular human immunodeficiency virus (HIV) testing was undertaken in these clinical trials. Although legitimate concerns exist about ART adherence and drug resistance associated with PrEP and TasP in real-world settings, efforts to curb the continuing HIV epidemic through use of these novel prevention strategies should move forward because the development and approval of newer drugs reserved for prevention might take many more years. Efforts must be made to monitor ART adherence and to intervene through counseling and other means in order to optimize adherence and retention in care, whenever necessary. Finally, further research involving the generalized epidemic is needed to determine when suboptimal drug use may occur and when regular testing and monitoring of the long-term consequences of ART use may not be routine.

BACKGROUND: Retaining patients in clinical care is necessary to ensure successful antiretroviral treatment (ART) outcomes. Among patients who discontinue care, some reenter care at a later stage, whereas others are or will be lost from follow-up. We examined risk factors for health care interruptions and loss to follow-up within a cohort receiving ART in Uganda. METHODS: Using a large hospital cohort providing free universal ART and HIV clinical care, we assessed characteristics and risk factors for treatment interruptions, defined as a 12-month absence from care at Mildmay, and loss to follow-up, defined as absence from care greater than 12 months without reengagement in care at Mildmay. We included patients aged 14 years and above. We assessed these outcomes over time using Kaplan-Meier analysis and multivariable regression. RESULTS: Of 6970 eligible patients, 784 (11.2%) had a health care interruption of at least 12 months and 217 (3.1%) were lost to follow-up. Patients experiencing health care interruptions had higher baseline CD4 T-cell counts at ART initiation, defined as ≥ 250 cells per cubic millimeter [odds ratio (OR): 1.29, 95% confidence intervals (CI): 1.11 to 1.50], and lower levels of education (OR: 1.32, 95% CI: 1.09 to 1.61). Adolescents were much more likely to be lost to follow-up (OR: 3.11, 95% CI: 2.23 to 4.34). In contrast, having a partner (OR: 0.22, 95% CI: 0.16 to 0.31) or being sexually active at baseline (OR: 0.40, 95% CI: 0.28 to 0.55) was protective of loss to follow-up. CONCLUSIONS: Within this cohort, long periods of unsupervised health care interruptions were common.

Challenges to scaling up treatment as prevention (TasP) of HIV transmission are considerable in the developing-world context and include accessing at-risk populations, human resource shortages, adherence and retention in care, access to newer treatments, measurement of treatment effects, and long-term sustainable funding. Optimism about ending AIDS needs to be tempered by the realities of the logistic challenges of strengthening health systems in countries most affected and by balancing TasP with overall combination prevention approaches.

To determine factors that influence excision treatment outcome and recurrence of cervical squamous intraepithelial lesions (SIL) in women living with HIV infection, we analysed 1848 women who underwent excision treatment of cervical SIL at Tygerberg Hospital, Cape Town, South Africa. We compared treatment failure defined as presence of cervical intraepithelial neoplasia (CIN) I (presence of CIN I or higher at first follow-up after excision treatment) and post-excision recurrence of lesions (at one year or later) between women of HIV-positive, -negative or unknown status and examined factors associated with excision treatment outcome and recurrence. HIV-infected women experienced higher treatment failure than uninfected women (53.8% versus 26.9%, P< 0.001). At treatment failure, more HIV-infected women had low-grade squamous intraepithelial lesion (LSIL) compared with uninfected women (64.9% versus 37.3%, P < 0.001). Treatment failure did not differ with the type of excision used in HIV-infected women. HIV-infected women were more likely to experience recurrence of lesions after excision treatment than uninfected women (hazard ratio 1.95, 95% confidence interval [CI] 1.59-2.39; P < 0.001). Antiretroviral therapy (ART) initiated before excision biopsy had a strong protective effect against recurrence (hazard ratio 0.70, 95% CI 0.55-0.89; P = 0.006). Our data suggest that women with cervical SIL initiated on ART earlier may be expected to have better long-term excision treatment outcome. Close follow-up should be maintained after cervical excision treatment, especially in a setting of high HIV prevalence.

Background Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities. Methods and Findings We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART. We calculated pooled proportions of reported barriers to adherence per age group (adults, adolescents, and children). We included data from 125 studies that provided information about adherence barriers for 17,061 adults, 1,099 children, and 856 adolescents. We assessed differences according to geographical location and level of economic development. The most frequently reported individual barriers included forgetting (adults 41.4%, 95% CI 37.3%–45.4%; adolescents 63.1%, 95% CI 46.3%–80.0%; children/caregivers 29.2%, 95% CI 20.1%–38.4%), being away from home (adults 30.4%, 95% CI 25.5%–35.2%; adolescents 40.7%, 95% CI 25.7%–55.6%; children/caregivers 18.5%, 95% CI 10.3%–26.8%), and a change to daily routine (adults 28.0%, 95% CI 20.9%–35.0%; adolescents 32.4%, 95% CI 0%–75.0%; children/caregivers 26.3%, 95% CI 15.3%–37.4%). Depression was reported as a barrier to adherence by more than 15% of patients across all age categories (adults 15.5%, 95% CI 12.8%–18.3%; adolescents 25.7%, 95% CI 17.7%–33.6%; children 15.1%, 95% CI 3.9%–26.3%), while alcohol/substance misuse was commonly reported by adults (12.9%, 95% CI 9.7%–16.1%) and adolescents (28.8%, 95% CI 11.8%–45.8%). Secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of adults and children across all regions (adults 13.6%, 95% CI 11.9%–15.3%; children/caregivers 22.3%, 95% CI 10.2%–34.5%). Among adults, feeling sick (15.9%, 95% CI 13.0%–18.8%) was a more commonly cited barrier to adherence than feeling well (9.3%, 95% CI 7.2%–11.4%). Health service–related barriers, including distance to clinic (adults 17.5%, 95% CI 13.0%–21.9%) and stock outs (adults 16.1%, 95% CI 11.7%–20.4%), were also frequently reported. Limitations of this review relate to the fact that included studies differed in approaches to assessing adherence barriers and included variable durations of follow up. Studies that report self-reported adherence will likely underestimate the frequency of non-adherence. For children, barriers were mainly reported by caregivers, which may not correspond to the most important barriers faced by children. Conclusions Patients on ART face multiple barriers to adherence, and no single intervention will be sufficient to ensure that high levels of adherence to treatment and virological suppression are sustained. For maximum efficacy, health providers should consider a more triaged approach that first identifies patients at risk of poor adherence and then seeks to establish the support that is needed to overcome the most important barriers to adherence., In this systematic review and meta-analysis, Nathan Ford and colleagues assess the most frequently reported barriers by patients experiencing challenges adhering to antiretroviral therapy., Author Summary Why Was This Study Done? Despite more than two decades of research on adherence to antiretroviral therapy (ART) and more than 17 million HIV-positive individuals on treatment, adherence to ART remains a major challenge. This review aimed to assess the most frequently reported barriers to adherence by patients experiencing adherence challenges. What Did the Researchers Do and Find? Published data from 125 studies on patient-reported barriers to adherence were systematically reviewed and analyzed by age group. The most frequently reported individual barriers across all age groups included forgetting, being away from home, and a change to daily routine. Depression was reported as a barrier to adherence by more than 15% of patients across all age categories, while alcohol/substance misuse was commonly reported as a barrier by adults and adolescents. With respect to contextual barriers, secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of patients across all regions. Health service–related barriers were frequently reported, including distance to clinic and stock outs. What Do These Findings Mean? Evidence-based interventions exist that may address many of the most common patient-reported barriers to adherence. However, no single intervention will be sufficient to ensure that high levels of adherence to treatment and virological suppression are sustained. Health providers should consider a more triaged approach that first identifies patients at risk of poor adherence and then seeks to establish the support that is needed to overcome the most important barriers to adherence. Several key health service improvements are also required to ensure that patients are able to consistently access ART.

Jean B Nachega,1,2 Donald Skinner,3 Larissa Jennings,4 Jessica F Magidson,5 Frederick L Altice,6 Jessica G Burke,7 Richard T Lester,8 Olalekan A Uthman,9,10 Amy R Knowlton,11 Mark F Cotton,12 Jean R Anderson,13 Gerhard B Theron14 1Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA; 2Department of Medicine, Centre for Infectious Diseases, and ACTG Clinical Trial Unit (CTU)/Family Clinical Research Unit (FAMCRU), 3Research on Health and Society, Department of Interdisciplinary Health Studies, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; 4Social and Behavioral Interventions Program, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 5Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 6Division of Infectious Diseases, AIDS Program, Yale University School of Medicine, New Haven, CT, 7Department of Behavioral and Community Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA; 8Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, BC, Canada; 9Warwick Centre for Applied Health Research and Delivery (WCAHRD), Division of Health Sciences, Warwick Medical School, The University of Warwick, Coventry, UK; 10Centre for Evidence-Based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; 11Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 12Department of Pediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; 13Department of Obstetrics and Gynecology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; 14Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa Objective: To examine the acceptability and feasibility of mobile health (mHealth)/short message service (SMS) and community-based directly observed antiretroviral therapy (cDOT) as interventions to improve antiretroviral therapy (ART) adherence for preventing mother-to-child human immunodeficiency virus (HIV) transmission (PMTCT). Design and methods: A mixed-method approach was used. Two qualitative focus group discussions with HIV-infected pregnant women (n=20) examined the acceptability and feasibility of two ART adherence interventions for PMTCT: 1) SMS text messaging and 2) patient-nominated cDOT supporters. Additionally, 109 HIV-infected, pregnant South African women (18–30 years old) receiving PMTCT services under single-tablet antiretroviral therapy regimen during pregnancy and breastfeeding and continuing for life (“Option B+”) were interviewed about mobile phone access, SMS use, and potential treatment supporters. Setting: A community primary care clinic in Cape Town, South Africa. Participants: HIV-infected pregnant women. Main outcomes: Acceptability and feasibility of mHealth and cDOT interventions. Results: Among the 109 women interviewed, individual mobile phone access and SMS use were high (>90%), and 88.1% of women were interested in receiving SMS ART adherence support messages such as reminders, motivation, and medication updates. Nearly all women (95%) identified at least one person close to them to whom they had disclosed their HIV status and would nominate as a cDOT supporter. Focus group discussions revealed that cDOT supporters and adherence text messages were valued, but some concerns regarding supporter time availability and risk of unintended HIV status disclosure were expressed. Conclusion: mHealth and/or cDOT supporter as interventions to improve ART adherence are feasible in this setting. However, safe HIV status disclosure to treatment supporters and confidentiality of text messaging content about HIV and ART were deemed crucial. Keywords: HIV, AIDS, pregnancy, short messaging system, social support

Introduction : It is unclear whether using peers can improve adherence to antiretroviral therapy (ART). To construct the World Health Organization’s global guidance on adherence interventions, we conducted a systematic review and network meta-analysis to determine the effectiveness of using peers for achieving adequate adherence and viral suppression. Methods : We searched for randomized clinical trials of peer-based interventions to promote adherence to ART in HIV populations. We searched six electronic databases from inception to July 2015 and major conference abstracts within the last three years. We examined the outcomes of adherence and viral suppression among trials done worldwide and those specific to low- and middle-income countries (LMIC) using pairwise and network meta-analyses. Results and discussion : Twenty-two trials met the inclusion criteria. We found similar results between pairwise and network meta-analyses, and between the global and LMIC settings. Peer supporter+Telephone was superior in improving adherence than standard-of-care in both the global network (odds-ratio [OR]=4.79, 95% credible intervals [CrI]: 1.02, 23.57) and the LMIC settings (OR=4.83, 95% CrI: 1.88, 13.55). Peer support alone, however, did not lead to improvement in ART adherence in both settings. For viral suppression, we found no difference of effects among interventions due to limited trials. Conclusions : Our analysis showed that peer support leads to modest improvement in adherence. These modest effects may be due to the fact that in many settings, particularly in LMICs, programmes already include peer supporters, adherence clubs and family disclosures for treatment support. Rather than introducing new interventions, a focus on improving the quality in the delivery of existing services may be a more practical and effective way to improve adherence to ART. Keywords: antiretroviral therapy adherence; peer interventions; viral suppression; systematic review; meta-analysis; network meta-analysis. To access the supplementary material to this article please see Supplementary Files in the column to the right (under Article Tools). (Published: 30 November 2016) Citation: Kanters S et al. Journal of the International AIDS Society 2016, 19 :21141 http://www.jiasociety.org/index.php/jias/article/view/21141 | http://dx.doi.org/10.7448/IAS.19.1.21141

Summary Background High adherence to antiretroviral therapy is crucial to the success of HIV treatment. We evaluated comparative effectiveness of adherence interventions with the aim of informing the WHO's global guidance on interventions to increase adherence. Methods For this systematic review and network meta-analysis, we searched for randomised controlled trials of interventions that aimed to improve adherence to antiretroviral therapy regimens in populations with HIV. We searched Cochrane Central Register of Controlled Trials, Embase, and MEDLINE for reports published up to July 16, 2015, and searched major conference abstracts from Jan 1, 2013, to July 16, 2015. We extracted data from eligible studies for study characteristics, interventions, patients' characteristics at baseline, and outcomes for the study populations of interest. We used network meta-analyses to compare adherence and viral suppression for all study settings (global network) and for studies in low-income and middle-income countries only (LMIC network). Findings We obtained data from 85 trials with 16 271 participants. Short message service (SMS; text message) interventions were superior to standard of care in improving adherence in both the global network (odds ratio [OR] 1·48, 95% credible interval [CrI] 1·00−2·16) and in the LMIC network (1·49, 1·04−2·09). Multiple interventions showed generally superior adherence to single interventions, indicating additive effects. For viral suppression, only cognitive behavioural therapy (1·46, 1·05−2·12) and supporter interventions (1·28, 1·01−1·71) were superior to standard of care in the global network; none of the interventions improved viral response in the LMIC network. For the global network, the time discrepancy (whether the study outcome was measured during or after intervention was withdrawn) was an effect modifier for both adherence to antiretroviral therapy (coefficient estimate −0·43, 95% CrI −0·75 to −0·11) and viral suppression (−0·48; −0·84 to −0·12), suggesting that the effects of interventions wane over time. Interpretation Several interventions can improve adherence and viral suppression; generally, their estimated effects were modest and waned over time. Funding WHO.

To describe the incidence of rapid kidney function decline (RKFD), and stage 3 chronic kidney disease (CKD) in HIV-1-infected adults initiated on tenofovir-containing antiretroviral therapy.A retrospective cohort study at the infectious diseases clinic of Tygerberg Academic Hospital in Cape Town, South Africa. Patients with more than 3 ml/min per year decline in estimated glomerular filtration were classified as having RKFD, and stage 3 CKD was defined as a value less than 60 ml/min per 1.73 m. We used logistic and Cox proportional hazards regression models to determine factors associated with RKFD and stage 3 CKD.Of 650 patients, 361 (55%) experienced RKFD and 15 (2%) developed stage 3 CKD during a median interquartile range follow-up time of 54 (46.6-98) weeks. For every 10-year increase in age and 10 ml/min lower baseline estimated glomerular filtration, the odds of RKFD increased by 70% [adjusted odds ratio = 1.70, 95% confidence interval (CI) 1.36-2.13] and 57% (adjusted odds ratio = 1.57, 95% CI 1.38-1.80), respectively. Each 10-year older age was associated with a 1.90-fold increased risk of developing stage 3 CKD (adjusted hazard ratio = 1.90, 95% CI: 1.10-3.29). Women had about four-fold greater risk of stage 3 CKD compared with men (adjusted hazard ratio = 3.96, 95% CI: 1.06-14.74).About half of our study population developed RKFD but only 2% progressed to stage 3 CKD. Approaches that provide balanced allocation of limited resources toward screening and monitoring for kidney dysfunction and HIV disease management are critically needed in this setting.

BACKGROUND: Established in 2000, Millennium Development Goal 4 (MDG4) catalysed extraordinary political, financial, and social commitments to reduce under-5 mortality by two-thirds between 1990 and 2015. At the country level, the pace of progress in improving child survival has varied markedly, highlighting a crucial need to further examine potential drivers of accelerated or slowed decreases in child mortality. The Global Burden of Disease 2015 Study (GBD 2015) provides an analytical framework to comprehensively assess these trends for under-5 mortality, age-specific and cause-specific mortality among children under 5 years, and stillbirths by geography over time. METHODS: Drawing from analytical approaches developed and refined in previous iterations of the GBD study, we generated updated estimates of child mortality by age group (neonatal, post-neonatal, ages 1-4 years, and under 5) for 195 countries and territories and selected subnational geographies, from 1980-2015. We also estimated numbers and rates of stillbirths for these geographies and years. Gaussian process regression with data source adjustments for sampling and non-sampling bias was applied to synthesise input data for under-5 mortality for each geography. Age-specific mortality estimates were generated through a two-stage age-sex splitting process, and stillbirth estimates were produced with a mixed-effects model, which accounted for variable stillbirth definitions and data source-specific biases. For GBD 2015, we did a series of novel analyses to systematically quantify the drivers of trends in child mortality across geographies. First, we assessed observed and expected levels and annualised rates of decrease for under-5 mortality and stillbirths as they related to the Soci-demographic Index (SDI). Second, we examined the ratio of recorded and expected levels of child mortality, on the basis of SDI, across geographies, as well as differences in recorded and expected annualised rates of change for under-5 mortality. Third, we analysed levels and cause compositions of under-5 mortality, across time and geographies, as they related to rising SDI. Finally, we decomposed the changes in under-5 mortality to changes in SDI at the global level, as well as changes in leading causes of under-5 deaths for countries and territories. We documented each step of the GBD 2015 child mortality estimation process, as well as data sources, in accordance with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). FINDINGS: Globally, 5·8 million (95% uncertainty interval [UI] 5·7-6·0) children younger than 5 years died in 2015, representing a 52·0% (95% UI 50·7-53·3) decrease in the number of under-5 deaths since 1990. Neonatal deaths and stillbirths fell at a slower pace since 1990, decreasing by 42·4% (41·3-43·6) to 2·6 million (2·6-2·7) neonatal deaths and 47·0% (35·1-57·0) to 2·1 million (1·8-2·5) stillbirths in 2015. Between 1990 and 2015, global under-5 mortality decreased at an annualised rate of decrease of 3·0% (2·6-3·3), falling short of the 4·4% annualised rate of decrease required to achieve MDG4. During this time, 58 countries met or exceeded the pace of progress required to meet MDG4. Between 2000, the year MDG4 was formally enacted, and 2015, 28 additional countries that did not achieve the 4·4% rate of decrease from 1990 met the MDG4 pace of decrease. However, absolute levels of under-5 mortality remained high in many countries, with 11 countries still recording rates exceeding 100 per 1000 livebirths in 2015. Marked decreases in under-5 deaths due to a number of communicable diseases, including lower respiratory infections, diarrhoeal diseases, measles, and malaria, accounted for much of the progress in lowering overall under-5 mortality in low-income countries. Compared with gains achieved for infectious diseases and nutritional deficiencies, the persisting toll of neonatal conditions and congenital anomalies on child survival became evident, especially in low-income and low-middle-income countries. We found sizeable heterogeneities in comparing observed and expected rates of under-5 mortality, as well as differences in observed and expected rates of change for under-5 mortality. At the global level, we recorded a divergence in observed and expected levels of under-5 mortality starting in 2000, with the observed trend falling much faster than what was expected based on SDI through 2015. Between 2000 and 2015, the world recorded 10·3 million fewer under-5 deaths than expected on the basis of improving SDI alone. INTERPRETATION: Gains in child survival have been large, widespread, and in many places in the world, faster than what was anticipated based on improving levels of development. Yet some countries, particularly in sub-Saharan Africa, still had high rates of under-5 mortality in 2015. Unless these countries are able to accelerate reductions in child deaths at an extraordinary pace, their achievement of proposed SDG targets is unlikely. Improving the evidence base on drivers that might hasten the pace of progress for child survival, ranging from cost-effective intervention packages to innovative financing mechanisms, is vital to charting the pathways for ultimately ending preventable child deaths by 2030. FUNDING: Bill & Melinda Gates Foundation. Erratum: Department of Error, The Lancet,Volume 389, Issue 10064, 2017, Page e1. DOI: 10.1016/S0140-6736(16)32608-3

Objective The impact of severe mental illness (SMI) on retention in HIV care remains uncertain. We aimed to measure the association between SMI at antiretroviral therapy (ART) initiation and subsequent retention in care in HIV-infected Ugandan adults. Method We conducted cohort study of 773 patients who initiated ART between January 2005 and July 2009 at the Butabika HIV clinic in Kampala, Uganda. SMI was defined as any clinically diagnosed organic brain syndrome, affective disorder or psychotic disorder. We used Kaplan–Meier and Cox proportional hazards analysis to evaluate the association between SMI and retention in care. Results The prevalence of SMI at ART initiation was 23%. Patients with SMI at baseline were similar to those without SMI in terms of age (median [IQR]: 35 [28–40] vs. 35 [30–40], P = 0.03), sex (36% vs. 35% female, P = 0.86) and baseline CD4+ T-cell count (112 [54–175] vs. 120 [48–187] cells/mm3, P = 0.86). At 12 months after ART initiation, Kaplan–Meier estimates of continuous retention in care were 65% (95% confidence interval, CI: 31–39%) among patients without SMI, vs. 47% (95% CI: 39–55%) among those with SMI (P 0.05). In multivariable analysis, the only baseline variable independently associated with breakage of continuous care was SMI (HR = 1.58, 95% CI: 1.06─2.33). Conclusions Severe mental illness at ART initiation is associated with worse retention in HIV care in this urban Ugandan referral hospital. As ART is scaled up across sub-Saharan Africa, greater attention must be paid to the burden of mental illness and its impact on retention in care. Objectif L'impact de la maladie mentale severe (MMS) sur la retention dans les soins du VIH reste incertain. Nous avons cherche a mesurer l'association entre la MMS a l'initiation de la therapie antiretrovirale (ART) et la retention ulterieure dans les soins chez les adultes ougandais infectes par le VIH. Methode Nous avons mene une etude de cohorte sur 773 patients qui ont commence l’ART entre janvier 2005 et juillet 2009 a la clinique VIH de Butabika a Kampala, en Ouganda. La MMS a ete definie comme tout syndrome cerebral organique cliniquement diagnostique, le trouble affectif ou psychotique. Nous avons utilise l'analyse des risques proportionnels de Kaplan–Meier et Cox pour evaluer l'association entre la MMS et la retention dans les soins. Resultats La prevalence de la MMS a l'initiation de l'ART etait de 23%. Les patients atteints de MMS au depart etaient semblables a ceux sans MMS en termes d’âge [mediane (IQR): 35 (28–40) vs. 35 (30–40), P = 0,03], de sexe (36% contre 35% de femmes, P = 0,86) et de numeration de base des cellules T CD4+ [112 (54–175) vs. 120 (48–187) cellules/mm3, P = 0,86]. A 12 mois apres l'initiation de l'ART, les estimations de Kaplan–Meier pour la retention continue dans les soins etaient de 65% (intervalle de confiance a 95% IC: 31-39%) chez les patients sans MMS, contre 47% (IC95%: 39–55%) chez ceux avec une MMS (P 0,05). Dans l'analyse multivariee, la seule variable de base independamment associee a une rupture de la continuite des soins etait la MMS (HR = 1,58; IC95%: 1,06–2,33). Conclusions La MMS a l'initiation de l’ART est associee a une plus mauvaise retention dans le traitement du VIH dans cet hopital urbain de reference ougandais. Comme l’ART est deployee a travers l’Afrique subsaharienne, une plus grande attention devrait etre accordee a la charge de morbidite de la maladie mentale et son impact sur la retention dans les soins. Objetivo El impacto de la enfermedad mental severa (EMS) sobre la retencion dentro de los cuidados para VIH continua siendo incierto. Buscabamos medir la asociacion entre EMS y la iniciacion de la terapia antirretroviral (TAR) y la retencion subsecuente, en adultos infectados con VIH en Uganda. Metodos Hemos realizado un estudio de cohortes con 773 pacientes que iniciaron TAR entre Enero del 2005 y Julio del 2009 en la Clinica Butabika para VIH en Kampala, Uganda. La EMS se definio como un sindrome cerebral organico con diagnostico clinico, desorden afectivo, o desorden psicotico. Utilizamos un analisis Kaplan-Meier y un modelo de riesgos proporcionales de Cox para evaluar la asociacion entre EMS y la retencion en los cuidados para VIH. Resultados La prevalencia de EMS al comienzo del TAR era del 23%. Los pacientes con EMS al comienzo del estudio eran similares a aquellos sin EMS en terminos de edad (mediana [IQR]: 35 [28-40] vs. 35 [30-40], P = 0.03), sexo (36% vs. 35% mujer, P = 0.86), y conteo de celulas T CD4 + al comienzo del estudio (112 [54-175] vs. 120 [48-187] celulas/mm3, P = 0.86). Doce meses despues del inicio del TAR, los calculos de Kaplan-Meier de retencion continuada en los cuidados para VIH eran del 65% (95% intervalo de confianza, IC: 31-39%) entre pacientes sin EMS, versus 47% (95% IC: 39–55%) entre aquellos con EMS (P 0.05). En un analisis multivariado, la unica variable presente al comienzo del estudio, independientemente asociada con el interrumpir los cuidados continuos era la EMS (HR = 1.58, IC 95%: 1.06–2.33). Conclusiones Una enfermedad mental severa al inicio del TAR estaba asociada con una peor retencion en los cuidados para VIH en este hospital de referencia de Uganda. A medida que se extienda el TAR en Africa subsahariana, se debera prestar una mayor atencion a la carga de enfermedad mental y a su impacto sobre la retencion de cuidados.

Currently, boosted protease inhibitor-containing regimens are the only option after first-line regimen failure available for patients in most resource-limited settings, yet little is known about long-term adherence and outcomes.We enrolled patients with virologic failure (VF) who initiated lopinavir/ritonavir-containing second-line antiretroviral therapy (ART). Medication possession ratios were calculated using pharmacy refill dates. Factors associated with 12-month second-line virologic suppression [viral load (VL)50 copies/mL] and adherence were determined.One hundred six patients (median CD4 count and VL at failure: 153 cells/mm(3) and 28,548 copies/mL, respectively) were enrolled. Adherence improved after second-line ART switch (median adherence 6 months prior, 67%; median adherence during initial 6 months of second-line ART, 100%; P = 0.001). Higher levels of adherence during second-line ART was associated with virologic suppression at month 12 of ART (odds ratio 2.5 per 10% adherence increase, 95% CI 1.3 to 4.8, P = 0.01). Time to virologic suppression was most rapid among patients with 91%-100% adherence compared with patients with 80%-90% and80% adherence (log rank test, P = 0.01). VF during 24 months of second-line ART was moderate (month 12: 25%, n = 32/126; month 18: 21%, n = 23/112; and month 24: 25%, n = 25/99).The switch to second-line ART in South Africa was associated with an improvement in adherence, however, a moderate ongoing rate of VF--among approximately 25% of patients receiving second-line ART patients at each follow-up interval--was a cause for concern. Adherence level was associated with second-line ART virologic outcome, helping explain why some patients achieved virologic suppression after switch and others did not.

This study aimed to investigate the progression and persistence of low-grade squamous intraepithelial lesions (SILs) in human immunodeficiency virus (HIV)-infected women.Study participants for this retrospective cohort study were 1,720 women who had LSIL as their first abnormal Pap smear. A comparison of the survival of LSIL without progression to high-grade SIL as progression-free time and the survival of SIL without clearance of the lesion as persistence of SIL was done for women of HIV-positive, HIV-negative, or unknown status using the Kaplan-Meier method. Multivariable Cox proportional hazards regression model was applied to identify independent risk factors for disease progression or persistence.We found progression of LSIL not different between HIV groups but that persistence occurred more in HIV-positive women (63.8% vs 35.0%, p.001). For the HIV group, antiretroviral therapy that was started before the first LSIL was associated with decreased risk for progression compared with no antiretroviral therapy (hazard ratio = 0.66, 95% CI = 0.54-0.81, p.001). Antiretroviral therapy also improved clearance when corrected for excision treatment and age (hazard ratio = 1.71, 95% CI = 1.29-2.27, p.001). Excision of LSIL reduced the risk of progression. In HIV-negative women, progression was reduced from 54.7% to 0.0% (p.001), and from 46.9% to 6.4% in HIV-positive women (p.001). Excision also reduced persistence in HIV-negative women from 39.5% to 7.1% (p = .001), but for HIV-positive women, the effect was smaller (from 66.3% to 45.5%, p.001).Antiretroviral treatment reduced the risk for progression and persistence of LSIL in HIV-infected women.