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Summary: Background: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: −22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models. Methods: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case–control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions. Findings: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: −17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: −17.9% to 89.6%), and further increased to 80.9% (95% CI: −17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker. Interpretation: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen. Funding: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV.

IntroductionNon-communicable diseases (NCDs) are a leading cause of morbidity and mortality in low-and middle- income countries (LMICs). Despite this, a lack of funding, training and mentorship for NCD investigators in LMICs exists. In an effort to gain knowledge and skills to address these gaps, participants from the Global Research on Implementation and Translation Science (GRIT), a consortium of studies in eight LMICs and their networks, attended the dissemination and implementation (D&I) massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization to strengthen D&I capacity building. Here, we report on the pilot of this MOOC, which was implemented during the SARS COVID-19 pandemic from April- November 2020.MethodsParticipants completed pre-and post-training questionnaires to assess self-reported D&I competencies, general research skills, and research mentor access and quality. D&I competencies were measured by use of a scale developed for a US-based training program, with change in competency scores assessed by paired t test. We used univariate statistics to analyze the data for all other outcomes.ResultsOf the 247 participants enrolled, 32 (13%) completed all course requirements, 21 (9%) completed the pre-and post-surveys and are included in the analysis. D&I competency scores suggest improvement for those who had complete pre- and post-assessments. Trainee's average score on the full competency scale improved 1.45 points (0–5 scale) from pre- to post-test; all four subscales also showed evidence of improvements. There were small but not significant increases in competencies for grant writing, proposal/ manuscript writing and presentations from pre- to post-test assessment. 40% of trainees reported access to a research mentor and 12% reported access to a D&I specific mentor. Participants reported barriers (e.g., unstable internet access and challenges due to COVID-19) and facilitators (e.g., topical interests, collaboration with colleagues) to completing the MOOC.ConclusionsAlthough COVID-19 affected program usage and completion, the MOOC was feasible. We also had signals of effectiveness, meaning among LMIC participants completing the course, there was improvement in self-report D&I competency scores. Recommendations for future D&I trainings in LMICs include (1) adding more topic specific modules (i.e., NCD research, general research skills) for scalability; (2) fostering more collaboration with participants across LMICs; and (3) establishing partnerships with D&I mentors for course participants.

Background: Globally, mental health disorders rank as the greatest cause of disability. Low and middle-income countries (LMICs) hold a disproportionate share of the mental health burden, especially as it pertains to depression. Depression is highly prevalent among those with non-communicable diseases (NCDs), creating a barrier to successful treatment. While some treatments have proven efficacy in LMIC settings, wide dissemination is challenged by multiple factors, leading researchers to call for implementation strategies to overcome barriers to care provision. However, implementation strategies are often not well defined or documented, challenging the interpretation of study results and the uptake and replication of strategies in practice settings. Assessing implementation strategy fidelity (ISF), or the extent to which a strategy was implemented as designed, overcomes these challenges. This study assessed fidelity of two implementation strategies (a ‘basic’ champion strategy and an ‘enhanced’ champion ​+ ​audit and feedback strategy) to improve the integration of a depression intervention, measurement based care (MBC), at 10 NCD clinics in Malawi. The primary goal of this study was to assess the relationship between the implementation strategies and MBC fidelity using a mixed methods approach. Methods: We developed a theory-informed mixed methods fidelity assessment that first combined an implementation strategy specification technique with a fidelity framework. We then created corresponding fidelity indicators to strategy components. Clinical process data and one-on-one in-depth interviews with 45 staff members at 6 clinics were utilized as data sources. Our final analysis used descriptive statistics, reflexive-thematic analysis (RTA), data merging, and triangulation to examine the relationship between ISF and MBC intervention fidelity. Results: Our mixed methods analysis revealed how ISF may moderate the relationship between the strategies and MBC fidelity. Leadership engagement and implementation climate were critical for clinics to overcome implementation barriers and preserve implementation strategy and MBC fidelity. Descriptive statistics determined champion strategy fidelity to range from 61 to 93% across the 10 clinics. Fidelity to the audit and feedback strategy ranged from 82 to 91% across the 5 clinics assigned to that condition. MBC fidelity ranged from 54 to 95% across all clinics. Although correlations between ISF and MBC fidelity were not statistically significant due to the sample of 10 clinics, associations were in the expected direction and of moderate effect size. A coefficient for shared depression screening among clinicians had greater face validity compared to depression screening coverage and functioned as a proximal indicator of implementation strategy success. Conclusion: Fidelity to the basic and enhanced strategies varied by site and were influenced by leadership engagement and implementation climate. Champion strategies may benefit from the addition of leadership strategies to help address implementation barriers outside the purview of champions. ISF may moderate the relationship between strategies and implementation outcomes.

IntroductionGlobal HIV infections due to HIV-1 recombinants are increasing and impede prevention and treatment efforts. Key populations suffer most new HIV infections, but their role in the spread of HIV-1 recombinants is unknown. We conducted a global analysis of the associations between key populations and HIV-1 recombinants.MethodsWe searched PubMed, EMBASE, CINAHL, and Global Health for HIV-1 subtyping studies published from 1/1/1990 to 31/12/2015. Unpublished data was collected through a global survey. We included studies with HIV-1 subtyping data of key populations collected during 1990-2015. Key populations assessed were heterosexual people (HET), men who have sex with men (MSM), people who inject drugs (PWID), vertical transmissions (VERT), commercial sex workers (CSW), and transfusion-associated infections (BLOOD). Logistic regression was used to determine associations of key populations with HIV-1 recombinants. Subgroup analyses were performed for circulating recombinant forms (CRFs), unique recombinant forms (URFs), regions, and time periods.ResultsEight hundred and eighty five datasets including 77,284 participants from 83 countries were included. Globally, PWID were associated with the greatest odds of recombinants and CRFs (OR 2.6 [95% CI 2.46–2.74] and 2.99 [2.83–3.16]), compared to HET. CSW were associated with increased odds of recombinants and URFs (1.59 [1.44–1.75] and 3.61 [3.15–4.13]). VERT and BLOOD were associated with decreased odds of recombinants (0.58 [0.54–0.63] and 0.43 [0.33–0.56]). MSM were associated with increased odds of recombinants in 2010–2015 (1.43 [1.35–1.51]). Subgroup analyses supported our main findings.DiscussionAs PWID, CSW, and MSM are associated with HIV-1 recombinants, increased preventative measures and HIV-1 molecular surveillance are crucial within these key populations.Systematic review registrationPROSPERO [CRD42017067164].

Abstract Introduction Multiple antiretroviral agents have demonstrated efficacy for human immunodeficiency virus (HIV) pre‐exposure prophylaxis (PrEP). As a result, clinical trials of novel agents have transitioned from placebo‐ to active‐controlled designs; however, active‐controlled trials do not provide an estimate of efficacy versus no use of PrEP. Counterfactual placebo comparisons using other data sources could be employed to provide this information. Methods We compared the active‐controlled study (HPTN 084) of injectable cabotegravir (CAB‐LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) among women from seven countries in Africa to three external, contemporaneous randomized HIV prevention trials from which we constructed counterfactual placebo estimates. We used direct standardization via analysis weights to achieve the same distribution of person‐years between the external study and HPTN 084, across strata predictive of HIV risk (country and selected risk covariates). We estimated prevention efficacy against a counterfactual placebo to provide information on the use of CAB‐LA and FTC/TDF compared to no intervention. We compared the counterfactual placebo findings for FTC/TDF to previous placebo‐controlled trials, adjusted for observed adherence to daily pills. Results Distribution of age and baseline prevalence of gonorrhoea and chlamydia were similar among matched counterfactual placebo and observed HPTN 084 arms after standardization. Counterfactual estimates of CAB‐LA versus placebo in all three settings showed a consistent risk reduction of 93%–94%, with lower bounds of the confidence intervals above 72%. Observed adherence (quantifiable tenofovir in plasma) in HPTN 084 was 54%–56%, and estimated efficacy of daily oral FTC/TDF against a counterfactual placebo was consistent with a predicted risk reduction of 39%–40% for this level of daily pill use. Conclusions Counterfactual placebo rates of HIV acquisition derived from external trial data in similar locations and time can be used to support estimates of placebo‐based efficacy of a novel HIV prevention agent. External trial data must be standardized to be representative of the clinical trial cohort testing the novel HIV prevention agent, accounting for confounders.

ABSTRACT Cryptococcus neoformans is the causative agent of cryptococcosis, a disease with poor patient outcomes that accounts for approximately 180,000 deaths each year. Patient outcomes may be impacted by the underlying genetics of the infecting isolate; however, our current understanding of how genetic diversity contributes to clinical outcomes is limited. Here, we leverage clinical, in vitro growth and genomic data for 284 C. neoformans isolates to identify clinically relevant pathogen variants within a population of clinical isolates from patients with human immunodeficiency virus (HIV)-associated cryptococcosis in Malawi. Through a genome-wide association study (GWAS) approach, we identify variants associated with the fungal burden and the growth rate. We also find both small and large-scale variation, including aneuploidy, associated with alternate growth phenotypes, which may impact the course of infection. Genes impacted by these variants are involved in transcriptional regulation, signal transduction, glycosylation, sugar transport, and glycolysis. We show that growth within the central nervous system (CNS) is reliant upon glycolysis in an animal model and likely impacts patient mortality, as the CNS yeast burden likely modulates patient outcome. Additionally, we find that genes with roles in sugar transport are enriched in regions under selection in specific lineages of this clinical population. Further, we demonstrate that genomic variants in two genes identified by GWAS impact virulence in animal models. Our approach identifies links between the genetic variation in C. neoformans and clinically relevant phenotypes and animal model pathogenesis, thereby shedding light on specific survival mechanisms within the CNS and identifying the pathways involved in yeast persistence. IMPORTANCE Infection outcomes for cryptococcosis, most commonly caused by C. neoformans, are influenced by host immune responses as well as by host and pathogen genetics. Infecting yeast isolates are genetically diverse; however, we lack a deep understanding of how this diversity impacts patient outcomes. To better understand both clinical isolate diversity and how diversity contributes to infection outcomes, we utilize a large collection of clinical C. neoformans samples that were isolated from patients enrolled in a clinical trial across 3 hospitals in Malawi. By combining whole-genome sequence data, clinical data, and in vitro growth data, we utilize genome-wide association approaches to examine the genetic basis of virulence. Genes with significant associations display virulence attributes in both murine and rabbit models, demonstrating that our approach can identify potential links between genetic variants and patho-biologically significant phenotypes.

Global HIV-1 genetic diversity forms a major obstacle to the development of an HIV vaccine. It may be necessary to employ subtype-specific HIV-1 vaccines in individual countries according to their HIV-1 subtype distribution. We estimated the global and regional need for subtype-specific HIV-1 vaccines. We took into account the proportions of different HIV-1 variants circulating in each country, the genetic composition of HIV-1 recombinants, and the different genome segments (gag, pol, env) that may be incorporated into vaccines. We modeled different scenarios according to whether countries would employ subtype-specific HIV-1 vaccines against (1) the most common subtype; (2) subtypes contributing more than 5% of HIV infections; or (3) all circulating subtypes. For therapeutic vaccines targeting the most common HIV-1 subtype in each country, 16.5 million doses of subtype C vaccine were estimated globally, followed by subtypes A (14.3 million) and B (4.2 million). A vaccine based on env required 2.6 million subtype E doses, and a vaccine based on pol required 4.8 million subtype G doses. For prophylactic vaccines targeting the most common HIV-1 subtype in each country, 1.9 billion doses of subtype A vaccine were estimated globally, followed by subtype C (1.1 billion) and subtype B (1.0 billion). A vaccine based on env required 1.2 billion subtype E doses, and a vaccine based on pol required 0.3 billion subtype G doses. If subtype-specific HIV-1 vaccines are also directed against less common subtypes in each country, vaccines targeting subtypes D, F, H, and K are also needed and would require up to five times more vaccine doses in total. We conclude that to provide global coverage, subtype-specific HIV-1 vaccines need to be directed against subtypes A, B, and C. Vaccines targeting env also need to include subtype E and those targeting pol need to include subtype G.

Abstract Background Mental health (MH) disorders in low and middle-income countries (LMICs) account for a large proportion of disease burden. While efficacious treatments exist, only 10% of those in need are able to access care. This treatment gap is fueled by structural determinants including inadequate resource allocation and prioritization, both rooted in a lack of research and policy capacity. The goal of the Sub-Saharan Africa Regional Partnership for Mental Health Capacity Building (SHARP), based in Malawi and Tanzania, is to address those research and policy-based determinants. Methods SHARP aims to (1) build implementation science skills and expertise among Malawian and Tanzanian researchers in the area of mental health; (2) ensure that Malawian and Tanzanian policymakers and providers have the knowledge and skills to effectively apply research findings on evidence-based mental health programs to routine practice; and (3) strengthen dialogue between researchers, policymakers, and providers leading to efficient and sustainable scale-up of mental health services in Malawi and Tanzania. SHARP comprises five capacity building components: introductory and advanced short courses, a multifaceted dialogue, on-the-job training, pilot grants, and “mentor the mentors” courses. Discussion Program evaluation includes measuring dose delivered and received, participant knowledge and satisfaction, as well as academic output (e.g., conference posters or presentations, manuscript submissions, grant applications). The SHARP Capacity Building Program aims to make a meaningful contribution in pursuit of a model of capacity building that could be replicated in other LMICs. If impactful, the SHARP Capacity Building Program could increase the knowledge, skills, and mentorship capabilities of researchers, policymakers, and providers regarding effective scale up of evidence-based MH treatment.

Abstract Background Heterogeneity in the immune response to parasite infection is mediated in part by differences in host genetics, gender, and age group. In infants and young children, ongoing immunological maturation often results in increased susceptibility to infection and variable responses to drug treatment, increasing the risk of complications. Even though significant age-associated effects on host cytokine responses to Plasmodium falciparum infection have been identified, age-associated effects on uncomplicated malaria infection and anti-malarial treatment remain poorly understood. Methods In samples of whole blood from a cohort of naturally infected malaria-positive individuals with non-severe falciparum malaria in Malawi (n = 63 total; 34 infants and young children 18 years old), blood cytokine levels and monocyte and dendritic cell frequencies were assessed at two timepoints: acute infection, and 4 weeks post anti-malarial treatment. The effects of age group, gender, and timepoint were modeled, and the role of these factors on infection and treatment outcomes was evaluated. Results Regardless of treatment timepoint, in this population age was significantly associated with overall blood haemoglobin, which was higher in adults, and plasma nitric oxide metabolites, IL-10, and TNF levels, which were higher in young children. There was a significant effect of age on the haemoglobin treatment response, whereby after treatment, levels increased in young children and decreased in adults. Furthermore, there were significant age-associated effects on treatment response for overall parasite load, IFN-γ, and IL-12(p40), and these effects were gender-dependent. Significant age effects on the overall levels and treatment response of myeloid dendritic cell frequencies were observed. In addition, within each age group, results showed continuous age effects on gametocyte levels (Pfs16), TNF, and nitric oxide metabolites. Conclusions In a clinical study of young children and adults experiencing natural falciparum malaria infection and receiving anti-malarial treatment, age-associated signatures of infection and treatment responses in peripheral blood were identified. This study describes host markers that may indicate, and potentially contribute to, differential post-treatment outcomes for malaria in young children versus adults.

Background: Availability and access to the detection of resistance to anti-tuberculosis drug sremains a significant challenge in Malawi due to limited diagnostic services. The Xpert® MTB/RIF can detect Mycobacterium tuberculosis and resistance to rifampicin in a single, rapid assay. Rifampicin-resistant M. tuberculosis has not been well studied in Malawi. Objectives: We aimed to determine mutations in the rifampicin resistance determining region (RRDR) of the rpoB gene of M. tuberculosis strains which were defined as resistant to rifampicin by the Xpert MTB/RIF assay. Methods: Rifampicin-resistant isolates from 43 adult patients (≥ 18 years) from various districts of Malawi were characterised for mutations in the RRDR (codons 507–533) of the rpoB gene by DNA sequencing. Results: Mutations were found in 37/43 (86%) of the resistant isolates in codons 511, 512, 513,516, 522, 526 and 531. The most common mutations were in codons 526 (38%), 531 (29.7%) and 516 (16.2%). Mutations were not found in 6/43 (14%) of the resistant isolates. No novel rpoB mutations other than those previously described were found among the rifampicin-resistant M. tuberculosis complex strains. Conclusion: This study is the first to characterise rifampicin resistance in Malawi. The chaintermination DNA sequencing employed in this study is a standard method for the determination of nucleotide sequences and can be used to confirm rifampicin resistance obtained using other assays, including the Xpert MTB/RIF. Further molecular cluster analysis, such as spoligotyping and DNA finger printing, is still required to determine transmission dynamics and the epidemiological link of the mutated strains.

Background: Xpert® MTB/RIF is a molecular test for the detection of Mycobacterium tuberculosis and rifampicin resistance. It is considered to be a great advance over smear microscopy and culture. However, there is very little information regarding the performance characteristics of Xpert MTB/RIF in Malawi. Objective: We aimed to evaluate the performance of Xpert MTB/RIF in a Malawian setting. Methods: Stored sputum pellets were processed on Xpert MTB/RIF between June 2012 andMay 2014. Results were compared to mycobacteria growth indicator tube and Löwenstein-Jensen cultures, LED fluorescent microscopy and GenoType® MTBDRplus assay. Rifampicinresistance was confirmed by DNA sequencing. Results: Of the 348 specimens with valid Xpert MTB/RIF results, 129/348 (37%) were smearpositive and 198/348 (57%) were culture-positive. Xpert MTB/RIF demonstrated a sensitivity of 93.8% (95% CI 89.4% – 96.8%) and specificity of 97.4% (95% CI 93.5% – 99.3%), with a positive predictive value of 97.8% (95% CI 94.6% – 99.4%) and a negative predictive value of 92.6% (95% CI 87.4% – 96.1%). Xpert MTB/RIF correctly identified 185/186 (99.5%) rifampicin sensitive and 2/2 (100%) rifampicin-resistant M. tuberculosis strains. Mutations were notdetected by sequencing in one isolate which was rifampicin resistant on Xpert MTB/RIF butsensitive on MTBDRplus. Four non-tuberculous mycobacteria grew from four smear-negativespecimens, namely, M. avium (n = 1) and M. intracellulare (n = 3). No cross-reactivity wasobserved with any of the non-tuberculous mycobacteria when using Xpert MTB/RIF. Conclusion: When fully implemented, Xpert MTB/RIF may have an impact on patient care inMalawi. The increased diagnostic yield of Xpert MTB/RIF over smear microscopy can increaselaboratory-confirmed tuberculosis detection and ensure that treatment is given to appropriateindividuals or groups.

Transmission of Mycobacterium tuberculosis (TB) in health settings threatens health care workers and people living with HIV in sub-Saharan Africa. Nosocomial transmission is reduced with implementation of infection control (IC) guidelines. The objective of this study is to describe implementation of TB IC measures in Malawi. We conducted a cross-sectional study utilizing anonymous health worker questionnaires, semi-structured interviews with facility managers, and direct observations at 17 facilities in central Malawi. Of 592 health care workers surveyed, 34% reported that all patients entering the facility were screened for cough and only 8% correctly named the four most common signs and symptoms of TB in adults. Of 33 managers interviewed, 7 (21%) and 1 (3%) provided the correct TB screening questions for use in adults and children, respectively. Of 592 health workers, only 2.4% had been screened for TB in the previous year. Most (90%) reported knowing their HIV status, 53% were tested at their facility of employment, and half reported they would feel comfortable receiving ART or TB treatment at their facility of employment. We conclude that screening is infrequently conducted and knowledge gaps may undercut its effectiveness. Further, health care workers do not routinely access TB and HIV diagnostic and treatment services at their facility of employment.

Nevirapine (NVP) is widely used in antiretroviral treatment (ART) of HIV-1 globally. The primary objective of the AA5208/OCTANE trial was to compare the efficacy of NVP-based versus lopinavir/ritonavir (LPV/r)-based initial ART.In seven African countries (Botswana, Kenya, Malawi, South Africa, Uganda, Zambia, and Zimbabwe), 500 antiretroviral-naïve HIV-infected women with CD4

Lighthouse Trust operates two, public, integrated HIV clinics, Lighthouse (LH) and Martin Preuss Center (MPC), in Lilongwe, Malawi. Approximately 20% of patients eligible for antiretroviral therapy (ART) do not start ART. We explore individual and geographic factors that influence whether ART-eligible patients initiate ART.Adult patients eligible for ART between 2008-2011 were included. Analysis was stratified by clinic. Using logistic regression, we evaluated factors associated with initiating ART including gender, age, body mass index (BMI), employment, tuberculosis (TB), eligible at initial registration, WHO stage, CD4, months in pre-ART care (from initial registration to eligibility date), and patient neighborhood distance to clinic.Of 14,216 study patients, 4841 were from LH; 9285 were from MPC. At LH and MPC, respectively, median age was 34.2 and 33.8 years; median BMI was 22.0 and 20.6; and median distance was 5.6 and 4.9 Km. In multivariate models, odds of starting ART was highest among those older than 35 years and those eligible for ART based on WHO stages 3-4 vs. those in WHO stages 1-2 with CD4

We systematically reviewed observational studies of early mortality post-antiretroviral therapy (ART) initiation in low- and middle-income countries (LMIC) in Asia, Africa, and Central and South America, as defined by the World Bank, to summarize what is known.Studies published in English between January 1996 and December 2010 were searched in Medline and EMBASE. Three independent reviewers examined studies of mortality within one year post-ART. An article was included if the study was conducted in a LMIC, participants were initiating ART in a non-clinical trial setting and were ≥15 years. Fifty studies were included; 38 (76%) from sub-Saharan Africa (SSA), 5 (10%) from Asia, 2 (4%) from the Americas, and 5 (10%) were multi-regional. Median follow-up time and pre-ART CD4 cell count ranged from 3-55 months and 11-192 cells/mm(3), respectively. Loss-to-follow-up, reported in 40 (80%) studies, ranged from 0.3%-27%. Overall, SSA had the highest pooled 12-month mortality probability of 0.17 (95% CI 0.11-0.24) versus 0.11 (95% CI 0.10-0.13) for Asia, and 0.07 (95% CI 0.007-0.20) for the Americas. Of 14 (28%) studies reporting cause-specific mortality, tuberculosis (TB) (5%-44%), wasting (5%-53%), advanced HIV (20%-37%), and chronic diarrhea (10%-25%) were most common. Independent factors associated with early mortality in 30 (60%) studies included: low baseline CD4 cell count, male sex, advanced World Health Organization clinical stage, low body mass index, anemia, age greater than 40 years, and pre-ART quantitative HIV RNA.Significant heterogeneity in outcomes and in methods of reporting outcomes exist among published studies evaluating mortality in the first year after ART initiation in LMIC. Early mortality rates are highest in SSA, and opportunistic illnesses such as TB and wasting syndrome are the most common reported causes of death. Strategies addressing modifiable risk factors associated with early death are urgently needed.