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The unprecedented and ongoing COVID-19 pandemic has exposed weaknesses in African countries' health systems. The impact of shifted focus on COVID-19 for the past 2 years on routine health services, especially those for the epidemics of Tuberculosis, HIV/AIDS and Malaria, have been dramatic in both quantity and quality.In this article, we reflect on the COVID-19 related disruptions on the Tuberculosis, HIV/AIDS and Malaria routine health services across Africa.The COVID-19 pandemic resulted in disruptions of routine health services and diversion of already limited available resources in sub-Saharan Africa. As a result, disease programs like TB, malaria and HIV have recorded gaps in prevention and treatment with the prospects of reversing gains made towards meeting global targets. The extent of the disruption is yet to be fully quantified at country level as most data available is from modelling estimates before and during the pandemic.Accurate country-level data is required to convince donors and governments to invest more into revamping these health services and help prepare for managing future pandemics without disruption of routine services. Increasing government expenditure on health is a critical part of Africa's economic policy. Strengthening health systems at various levels to overcome the negative impacts of COVID-19, and preparing for future epidemics will require strong visionary political leadership. Innovations in service delivery and technological adaptations are required as countries aim to limit disruptions to routine services.

Nearly two years since the start of the SARS-CoV-2 pandemic, which has caused over 5 million deaths, the world continues to be on high COVID-19 alert. The World Health Organization (WHO), in collaboration with national authorities, public health institutions and scientists have been closely monitoring and assessing the evolution of SARS-CoV-2 since January 2020 (WHO 2021a; WHO 2021b). The emergence of specific SARS-CoV-2 variants were characterised as Variant of Interest (VOI) and Variant of Concern (VOC), to prioritise global monitoring and research, and to inform the ongoing global response to the COVID-19 pandemic. The WHO and its international sequencing networks continuously monitor SARS-CoV-2 mutations and inform countries about any changes that may be needed to respond to the variant, and prevent its spread where feasible. Multiple variants of the virus have emerged and become dominant in many countries since January 2021, with the Alpha, Beta, Gamma and Delta variants being the most prominent to date. (Table 1).

Recurrent disease outbreaks caused by a range of emerging and resurging pathogens over the past decade reveal major gaps in public health preparedness, detection, and response systems in Africa. Underlying causes of recurrent disease outbreaks include inadequacies in the detection of new infectious disease outbreaks in the community, in rapid pathogen identification, and in proactive surveillance systems. In sub-Saharan Africa, where 70% of zoonotic outbreaks occur, there remains the perennial risk of outbreaks of new or re-emerging pathogens for which no vaccines or treatments are available. As the Ebola virus disease, COVID-19, and mpox (formerly known as monkeypox) outbreaks highlight, a major paradigm shift is required to establish an effective infrastructure and common frameworks for preparedness and to prompt national and regional public health responses to mitigate the effects of future pandemics in Africa.

COVID-19 underscores the need to reimagine North–South partnerships and redefine best practices for building public health and research capacity to address emergent health threats and pandemic preparedness in low- and-middle income countries (LMICs). Historically, outbreak and emergency responses have failed to ensure that the Global South has the autonomy and capacity to respond to public health threats in a timely and equitable manner. The COVID-19 response, however, has demonstrated that innovations and solutions in the Global South can not only fill resource and capacity gaps in LMICs but can also provide solutions to challenges globally. These innovations offer valuable lessons about strengthening local manufacturing capacity to produce essential diagnostic, treatment, and prevention tools; implementing high-quality research studies; expanding laboratory and research capacity; and promoting effective cooperation and governance. We discuss specific examples of capacity-building from Rwanda, South Africa, and Senegal. To fulfill promises made to the Global South during the COVID-19 pandemic, restore and resume health service delivery, and effectively prevent and respond to the next health threat, we need to prioritize equitable access to local manufacturing of basic health tools while building health systems capacities in the Global South.

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.

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.

The novel coronavirus disease 2019 (COVID-19) has rapidly spread to all 7 continents. Due to yet unknown reasons, the African continent has remained relatively unaffected. We discuss the importance of mitigating pan-continental spread in light of the fragile healthcare systems.

To examine environmental and human factors that affect the spatial and temporal dynamism of malaria in DRC's South-Kivu province.In a cross-sectional study conducted between 1 January 2010 and 31 December 2015, spatial distribution was determined through thematic maps of malaria attack rate. SatScan ™ software and Monte Carlo test were used to identify spatial risk clusters. Temporal evolutions were analysed using the Cleveland algorithm. Generalized Additive Models for Location Scale and Shape and negative binomial regression were used to assess the independent human and environmental factors associated with incident malaria.The cumulative annual incidence of malaria increased from 10 968/100 000 in 2013 to 15 501/100 000 in 2015 (P for trend ˂0.001); malaria lethality increased from 0.1% in 2013 to 0.3% in 2015 (P for trend = 0.62). Between 2010 and 2015, 18 of 34 health zones consistently reported the highest attack rates, which ranged from 25 000 to 50 000/100 000. Four risk clusters areas were identified, with relative risk (RR) of 1.2 to 3.0, from which malaria was reported continuously during each year. Factors significantly associated with malaria cases were agro-pisciculture practices (Incidence Risk Ratio [IRR]: 1.96; 95% CI: 1.23-3.13) and the presence of a lake in the health zone (IRR: 2.48, 95% CI: 1.51-4.42).Malaria control in this setting must be intensified in peri-lacustrine areas and those in which the population is intensively engaged in standing water-associated activities.Examiner les facteurs environnementaux et humains qui affectent le dynamisme spatial et temporel du paludisme dans la province du Sud-Kivu en RDC. MÉTHODES: Dans une étude transversale menée entre le 1La lutte contre le paludisme dans ce contexte doit être intensifiée dans les zones péri-lacustres et celles dans lesquelles la population est intensément engagée dans des activités liées à l'eau stagnante.

After a century of controversies on its usefulness in protection against TB, underlying mechanisms of action, and benefits in various groups and geographical areas, the BCG vaccine is yet again a focus of global attention- this time due to the global COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have shown that human CD4+ and CD8+ T-cells primed with a BCG-derived peptide developed high reactivity to its corresponding SARS-CoV-2-derived peptide. Furthermore, BCG vaccine has been shown to substantially increase interferon-gamma (IFN-g) production and its effects on CD4 + T-cells and these non-specific immune responses through adjuvant effect could be harnessed as cross protection against severe forms of COVID-19.The completion of ongoing BGG trials is important as they may shed light on the mechanisms underlying BCG-mediated immunity and could lead to improved efficacy, increased tolerance of treatment, and identification of other ways of combining BCG with other immunotherapies.

The October 2020 Global TB report reviews TB control strategies and United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York. Progress in TB care and prevention has been very slow. In 2019, TB remained the most common cause of death from a single infectious pathogen. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208, 000 deaths among people living with HIV. Adults accounted for 88% and children for 12% of people with TB. The WHO regions of South-East Asia (44%), Africa (25%), and the Western Pacific (18%) had the most people with TB. Eight countries accounted for two thirds of the global total: India (26%), Indonesia (8.5%), China (8.4%), the Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%) and South Africa (3.6%). Only 30% of the 3.5 million five-year target for children treated for TB was met. Major advances have been development of new all oral regimens for MDRTB and new regimens for preventive therapy. In 2020, the COVID-19 pandemic dislodged TB from the top infectious disease cause of mortality globally. Notably, global TB control efforts were not on track even before the advent of the COVID-19 pandemic. Many challenges remain to improve sub-optimal TB treatment and prevention services. Tuberculosis screening and diagnostic test services need to be ramped up. The major drivers of TB remain undernutrition, poverty, diabetes, tobacco smoking, and household air pollution and these need be addressed to achieve the WHO 2035 TB care and prevention targets. National programs need to include interventions for post-tuberculosis holistic wellbeing. From first detection of COVID-19 global coordination and political will with huge financial investments have led to the development of effective vaccines against SARS-CoV2 infection. The world now needs to similarly focus on development of new vaccines for TB utilizing new technological methods.

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.

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.

In the African context, there is a paucity of data on SARS-CoV-2 infection and associated COVID-19 in pregnancy. Given the endemicity of infections such as malaria, HIV, and tuberculosis (TB) in sub-Saharan Africa (SSA), it is important to evaluate coinfections with SARS-CoV-2 and their impact on maternal/infant outcomes. Robust research is critically needed to evaluate the effects of the added burden of COVID-19 in pregnancy, to help develop evidence-based policies toward improving maternal and infant outcomes. In this perspective, we briefly review current knowledge on the clinical features of COVID-19 in pregnancy; the risks of preterm birth and cesarean delivery secondary to comorbid severity; the effects of maternal SARS-CoV-2 infection on the fetus/neonate; and in utero mother-to-child SARS-CoV-2 transmission. We further highlight the need to conduct multicountry surveillance as well as retrospective and prospective cohort studies across SSA. This will enable assessments of SARS-CoV-2 burden among pregnant African women and improve the understanding of the spectrum of COVID-19 manifestations in this population, which may be living with or without HIV, TB, and/or other coinfections/comorbidities. In addition, multicountry studies will allow a better understanding of risk factors and outcomes to be compared across countries and subregions. Such an approach will encourage and strengthen much-needed intra-African, south-to-south multidisciplinary and interprofessional research collaborations. The African Forum for Research and Education in Health’s COVID-19 Research Working Group has embarked upon such a collaboration across Western, Central, Eastern and Southern Africa.

With increasing effectiveness of antiretroviral therapy, people with HIV (PWH) are living longer and the prevalence of older PWH continues to increase. Accordingly, PWH are experiencing an increased burden of age-related comorbidities. With this shifting demographics, clinicians and researchers face additional challenges in how to identify, address, and manage the complex intersections of HIV- and aging-related conditions. Established in 2009, the International Workshop on HIV and Aging brings together clinicians and researchers in cross-disciplinary fields along with community advocates and PWH to address the multidisciplinary nature of HIV and aging. This article summarizes plenary talks from the 10th Annual International Workshop on HIV and Aging, which took place in New York City on October 10 and 11, 2019. Presentation topics included the following: the burdens of HIV-associated comorbidities, aging phenotypes, community engagement, and loneliness; these issues are especially important for older PWH, considering the current COVID-19 pandemic. We also discuss broad questions and potential directions for future research necessary to better understand the interaction between HIV and aging.

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.

CITATION: Nachega, J. B. et al. 2020. Mobile health technology for enhancing the COVID-19 response in Africa : a potential game changer? American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-0506.

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

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.

Capacity building in low- and middle-income country (LMIC) institutions hinges on the delivery of effective mentorship. This study presents an overview of mentorship toolkits applicable to LMIC institutions identified through a scoping review. A scoping review approach was used to 1) map the extent, range, and nature of mentorship resources and tools available and 2) to identify knowledge gaps in the current literature. To identify toolkits, we collected and analyzed data provided online that met the following criteria: written in English and from organizations and individuals involved in global health mentoring. We searched electronic databases, including PubMed, Web of Science, and Google Scholar, and Google search engine. Once toolkits were identified, we extracted the available tools and mapped them to pre-identified global health competencies. Only three of the 18 identified toolkits were developed specifically for the LMIC context. Most toolkits focused on individual mentor–mentee relationships. Most focused on the domains of communication and professional development. Fewer toolkits focused on ethics, overcoming resource limitations, and fostering institutional change. No toolkits discussed strategies for group mentoring or how to adapt existing tools to a local context. There is a paucity of mentoring resources specifically designed for LMIC settings. We identified several toolkits that focus on aspects of individual mentor–mentee relationships that could be adapted to local contexts. Future work should focus on adaptation and the development of tools to support institutional change and capacity building for mentoring.

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.

Although significant progress has been made, the latest data from low- and middle-income countries show substantial gaps in reaching the third “90%” (viral suppression) of the UNAIDS 90-90-90 goals, especially among vulnerable and key populations. This article discusses critical gaps and promising, evidence-based solutions. There is no simple and/or single approach to achieve the last 90%. This will require multifaceted, scalable strategies that engage people living with human immunodeficiency virus, motivate long-term treatment adherence, and are community-entrenched and ‑supported, cost-effective, and tailored to a wide range of global communities.

Summary Background Group support psychotherapy (GSP) is a culturally sensitive intervention that aims to treat depression by enhancing social support, teaching coping skills, and income-generating skills. We compared GSP with group HIV education (GHE) for treatment of depression in people with HIV in Uganda. Methods In this open-label randomised controlled trial, we included men and women with HIV, aged 19 years or older, who met the Mini International Neuropsychiatric Interview criteria for major depression from an urban HIV care centre in Kitgum district, northern Uganda. Participants were randomly assigned to receive eight weekly sessions of either GSP or GHE. Randomisation was achieved by urn (men and women separately picked a paper containing the intervention allocation from a basket; ratio 1:1), and the intervention sessions were given to gender-specific groups. Participants were followed up immediately after the intervention and 6 months after the end of treatment. The primary outcomes were change in depressive symptom scores (measured with the Self-Reporting Questionnaire) and in function scores (measured with a locally developed method), analysed by intention to treat using cluster-adjusted t tests and permutation tests. This trial is registered with The Pan African Clinical Trials Registry, number PACTR201402000742370. Findings Between Jan 6, and Jan 20, 2014, we assessed 150 individuals, of whom 109 were randomly assigned to receive eight weekly sessions of either GSP (n=57) or GHE (n=52). Change in mean depression scores immediately after intervention did not differ between groups (mean difference −0·19, 95% CI −1·77 to 1·39, p=0·78). Mean function scores did not differ between groups either (0·24, −0·41 to 0·88; p=0·41). At 6 months after end of treatment, participants in the GSP group had lower mean depression scores than did those in the GHE group (−2·50, −3·98 to 1·02, p value=0·005), and higher function scores (0·74, −0·17 to 1·65, p=0·09) than did participants in the GHE group. No adverse events were reported. Interpretation The benefits of existing HIV educational interventions in HIV care services could be improved by the addition of GSP content. Potential benefits of the integration of GSP into existing HIV interventions, such as adherence counselling or group HIV educational programmes, should be addressed in future studies. Funding Grand Challenges Canada.

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.

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

Introduction Adolescents and youth receiving antiretroviral treatment (ART) in sub‐Saharan Africa have high attrition and inadequate ART outcomes, and evaluations of interventions improving ART outcomes amongst adolescents are very limited. Sustainable Development Goal (SDG) target 3c is to substantially increase the health workforce in developing countries. We measured the effectiveness and cost‐effectiveness of community‐based support (CBS) provided by lay health workers for adolescents and youth receiving ART in South Africa. Methods A retrospective cohort study including adolescents and youth who initiated ART at 47 facilities. Previously unemployed CBS‐workers provided home‐based ART‐related education, psychosocial support, symptom screening for opportunistic infections and support to access government grants. Outcomes were compared between participants who received CBS plus standard clinic‐based care versus participants who received standard care only. Cumulative incidences of all‐cause mortality and loss to follow‐up (LTFU), adherence measured using medication possession ratios (MPRs), CD4 count slope, and virological suppression were analysed using multivariable Cox, competing‐risks regression, generalized estimating equations and mixed‐effects models over five years of ART. An expenditure approach was used to determine the incremental cost of CBS to usual care from a provider perspective. Incremental cost‐effectiveness ratios were calculated as annual cost per patient‐loss (through death or LTFU) averted. Results Amongst 6706 participants included, 2100 (31.3%) received CBS. Participants who received CBS had reduced mortality, adjusted hazard ratio (aHR) = 0.52 (95% CI: 0.37 to 0.73; p

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

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.

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.

BACKGROUND HIV/AIDS has historically had a sex and gender-focused approach to prevention and care. Some evidence suggests that HIV-positive men have worse treatment outcomes than their women counterparts in Africa. METHODS We conducted a systematic review and meta-analysis of the effect of sex on the risk of death among participants enrolled in antiretroviral therapy (ART) programs in Africa since the rapid scale-up of ART. We included all cohort studies evaluating the effect of sex (male, female) on the risk of death among participants enrolled in regional and national ART programs in Africa. We identified these studies by searching MedLine, EMBASE, and Cochrane CENTRAL. We used a DerSimonian-Laird random-effects method to pool the proportions of men receiving ART and the hazard ratios for death by sex. RESULTS Twenty-three cohort studies, including 216 008 participants (79 892 men) contributed to our analysis. The pooled proportion of men receiving ART was 35% [95% confidence interval (CI): 33-38%]. The pooled hazard ratio estimate indicated a significant increase in the risk of death for men when compared to women [hazard ratio: 1.37 (95% CI: 1.28-1.47)]. This was consistent across sensitivity analyses. INTERPRETATION The proportion of men enrolled in ART programs in Africa is lower than women. Additionally, there is an increased risk of death for men enrolled in ART programs. Solutions that aid in reducing these sex inequities are needed.

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.

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.