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To determine the frequencies of HLA-B alleles in Ugandan patients in the NORA substudy of the DART trial and to compare HLA-B allele frequencies in those with and without clinically diagnosed hypersensitivity reaction (HSR). DNA-based HLA-B genotyping was used to determine HLA alleles in 247 participants who received abacavir, including all six participants ('cases') with clinically diagnosed abacavir HSR. The incidence of clinical abacavir HSR in this double-blinded study was 2.0% (6/300) in the abacavir group. As HLA-B*5701 was absent throughout the entire cohort, including the six HSR 'cases', an association could not be established between HLA-B*5701 and clinically diagnosed abacavir HSR. No other HLA-B*57 alleles were present among the six 'cases'. HLA-B*5703 was the most frequent HLA-B*57 allele among the abacavir-tolerant participants. The rate of clinical HSR was low, which may reflect the expected 2-3% clinical false-positive rate seen in previous double-blind randomized studies. The presumption that these cases may be false-positive abacavir HSR is supported by the fact that no HLA-B*5701 alleles were found in the abacavir group. Implementation of prospective HLA-B*5701 screening must be based on benefit/risk considerations within local practice. Clinical risk management remains paramount. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae is a leading and serious coinfection in adults with human immunodeficiency virus (HIV) infection, particularly in Africa. Prevention of this disease by vaccination with the current 23-valent polysaccharide vaccine is suboptimal. Protein conjugate vaccines offer a further option for protection, but data on their clinical efficacy in adults are needed. Methods: In this double-blind, randomized, placebo-controlled clinical efficacy trial, we studied the efficacy of a 7-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adolescents and adults who had recovered from documented invasive pneumococcal disease. Two doses of vaccine were given 4 weeks apart. The primary end point was a further episode of pneumococcal infection caused by vaccine serotypes or serotype 6A. Results: From February 2003 through October 2007, we followed 496 patients (of whom 44% were male and 88% were HIV-seropositive) for 798 person-years of observation. There were 67 episodes of pneumococcal disease in 52 patients, all in the HIV-infected subgroup. In 24 patients, there were 19 episodes that were caused by vaccine serotypes and 5 episodes that were caused by the 6A serotype. Of these episodes, 5 occurred in the vaccine group and 19 in the placebo group, for a vaccine efficacy of 74% (95% confidence interval [CI], 30 to 90). There were 73 deaths from any cause in the vaccine group and 63 in the placebo group (hazard ratio in the vaccine group, 1.18; 95% CI, 0.84 to 1.66). The number of serious adverse events within 14 days after vaccination was significantly lower in the vaccine group than in the placebo group (3 vs. 17, P=0.002), and the number of minor adverse events was significantly higher in the vaccine group (41 vs. 13, P=0.003). Conclusions: The 7-valent pneumococcal conjugate vaccine protected HIV-infected adults from recurrent pneumococcal infection caused by vaccine serotypes or serotype 6A. (Current Controlled Trials number, ISRCTN54494731.) [ABSTRACT FROM AUTHOR]

Background. We investigated virological response and the emergence of resistance in the Nevirapine or Abacavir (NORA) substudy of the Development of Antiretroviral Treatment in Africa (DART) trial. Methods. Six hundred symptomatic antiretroviral-naive human immunodeficiency virus (HIV)-infected adults (CD4 cell count, <200 cells/mm3) from 2 Ugandan centers were randomized to receive zidovudine-lamivudine plus abacavir or nevirapine. Virology was performed retrospectively on stored plasma samples at selected time points. In patients with HIV RNA levels >1000 copies/mL, the residual activity of therapy was calculated as the reduction in HIV RNA level, compared with baseline. Results. Overall, HIV RNA levels were lower in the nevirapine group than in the abacavir group at 24 and 48 weeks (P<.001), although no differences were observed at weeks 4 and 12. Virological responses were similar in the 2 treatment groups for baseline HIV RNA level <100,000 copies/mL. The mean residual activity at week 48 was higher for abacavir in the presence of the typically observed resistance pattern of thymidine analogue mutations (TAMs) and M184V (1.47 log10 copies/mL) than for nevirapine with M184V and nonnucleoside reverse-transcriptase inhibitor mutations, whether accompanied by TAMs (0.96 log10 copies/mL) or not (1.18 log10 copies/mL). Conclusions. There was more extensive genotypic resistance in both treatment groups than is generally seen in resource-rich settings. However, significant residual activity was observed among patients with virological failure, particularly those receiving zidovudine-lamivudine plus abacavir. [ABSTRACT FROM AUTHOR]

Background. We sought to investigate renal function in previously untreated symptomatic human immunodeficiency virus (HIV)-infected adults with CD4+ cell counts of !200 cells/mm3 who were undergoing antiretroviral therapy (ART) in Africa. Methods. The study was an observational analysis within a randomized trial of ART management strategies that included 3316 participants with baseline serum creatinine levels of ⩽360 mmol/L. Creatinine levels were measured before ART initiation, at weeks 4 and 12 of therapy, and every 12 weeks thereafter. We calculated estimated glomerular filtration rate (eGFR) using the Cockcroft-Gault formula. We analyzed the incidence of severely decreased eGFR (<30 mL/min/1.73 m2) and changes in eGFR to 96 weeks, considering demographic data, type of ART, and baseline biochemical and hematological characteristics as predictors, using random-effects models. Results. Sixty-five percent of the participants were women. Median values at baseline were as follows: age, 37 years; weight, 57 kg; CD4+ cell count, 86 cells/mm3; and eGFR, 89 mL/min/1.73 m2. Of the participants, 1492 (45%) had mild (⩾60 but <90 mL/min/1.73 m2) and 237 (7%) had moderate (⩾30 but ⩾60 mL/min/1.73 m2) impairments in eGFR. First-line ART regimens included zidovudine-lamivudine plus tenofovir disoproxil fumarate (for 74% of patients), nevirapine (16%), and abacavir (9%) (mostly nonrandomized allocation). After ART initiation, the median eGFR was 89-91 mL/min/1.73 m2 for the period from week 4 through week 96. Fifty-two participants (1.6%) developed severe reductions in eGFR by week 96; there was no statistically significant difference between these patients and others with respect to first-line ART regimen received (Pp.94). Lower baseline eGFR or hemoglobin level, lower body mass index, younger age, higher baseline CD4+ cell count, and female sex were associated with greater increases in eGFR over baseline, with small but statistically significant differences between regimens (P < .001 for all). Conclusions. Despite screening, mild-to-moderate baseline renal impairment was relatively common, but these participants had greatest increases in eGFR after starting ART. Severe eGFR impairment was infrequent regardless of ART regimen and was generally related to intercurrent disease. Differences between ART regimens with respect to changes in GFR through 96 weeks were of marginal clinical relevance, but investigating longer-term nephrotoxicity remains important. [ABSTRACT FROM AUTHOR]

We investigated the effect of RANTES polymorphisms on human immunodeficiency virus type 1 (HIV-1) disease progression in an urban population of Uganda. HIV-positive individuals homozygous for the INT1.1C polymorphism, which had been associated previously with low RANTES expression, were less likely to die than were those with other genotypes (hazard ratio, 0.53 [95% confidence interval, 0.33– 0.83]; P = .007). This report of a non-human leukocyte antigen genetic association with HIV-1 and/or acquired immunodeficiency syndrome disease progression in an African population reveals a genetic effect different from that reported elsewhere for African Americans and may impact therapeutic strategies targeting the RANTES pathway in HIV infection. [ABSTRACT FROM AUTHOR]

We investigated the immunogenicity of a 7-valent conjugate pneumococcal vaccine (CPV) in human immuno deficiency virus-infected Ugandan adults and measured the effect of past pneumococcal polysaccharide vaccine (PPV) receipt given as part of a controlled trial. Two doses of CPV, 4 weeks apart, were given to 54 past PPV recipients and 55 past placebo recipients (84% female; median CD4 cell count, 251 cells/μL [range, 1-936 cells/μL]). Postvaccination anticapsular immuno globulin G (IgG) concentrations were directly correlated with CD4 cell count (P< .01 for all serotypes). There were significant increases in anticapsular IgG concentrations for all serotypes after the first dose (P< .01) and for all serotypes except 14 and 9V after the second dose. Past receipt of PPV did not affect vaccine response. [ABSTRACT FROM AUTHOR]

Explores the role of primary health centers in provision of voluntary counseling and testing (VCT) of HIV-positive persons in Kenya. Identification of VCT as a key intervention on the struggle against HIV/AIDS; Accessibility of VCT services in the country; Significance of the study on the management and treatment of HIV/AIDS.

Investigates the effects of increased numbers of HIV/AIDS patients on rural district hospitals in South Africa. Means of reducing community burden of the AIDS disease; Impact of HIV on the health services; Access of patients to voluntary counseling and testing for HIV.

We assessed the impact of HIV-1 on malaria in the sub-Saharan African population. Relative risks for malaria in HIV-infected persons, derived from literature review, were applied to the HIV-infected population in each country, by age group, stratum of CD4 cell count, and urban versus rural residence. Distributions of CD4 counts among HIV-infected persons were modeled assuming a linear decline in CD4 after seroconversion. Averaged across 41 countries, the impact of HIV-1 was limited (although quantitatively uncertain) because of the different geographic distributions and contrasting age patterns of the 2 diseases. However, in Botswana, Zimbabwe, Swaziland, South Africa, and Namibia, the incidence of clinical malaria increased by ≤28% (95% confidence interval [CI] 14%-47%) and death increased by ≤114% (95% CI 37%-188%). These effects were due to high HIV-1 prevalence In rural areas and the locally unstable nature of malaria transmission that results in a high proportion of adult cases. [ABSTRACT FROM AUTHOR]

To investigate transmission of human herpesvirus (HHV)-8, 2546 mother-child pairs were recruited from rural clinics in South Africa and were tested for antibodies against lyric and latent HHV-8 antigens. The prevalence of antibodies in children increased with increasing maternal antibody titer (lyric, χ12 = 26, and P<.001; latent, χ12 = 55, and P<.001). HHV-8 DNA was detectable in 145 of 978 maternal saliva samples (mean virus load, 488,450 copies/mL; range, 1550–660,000 copies/mL) and in 12 of 43 breast-milk samples (mean virus load, 5800 copies/mL; range, 1550–12,540 copies/mL). The prevalence of HHV-8 DNA in maternal saliva was unrelated to latent anti-HHV-8 antibody status but was higher in mothers with the highest titers of lyric antibodies than in other mothers (34% vs. 8%; P < .001). The prevalence of lyric anti-HHV-8 antibodies in children was 13% (70/528) if the mother did not have HHV-8 in saliva and was 29% (8/28) if the mother had a high HHV-8 load (>50,000 copies/mL) in saliva (odds ratio, 2.6; 95% confidence interval, 1.1–6.2). The presence of HHV-8 DNA in maternal saliva was unrelated to latent antibodies in children. Saliva could be a route of transmission of HHV-8 from person to person, although other routes cannot be ruled out. [ABSTRACT FROM AUTHOR]

Intersectionality pinpoints intersecting factors that empower or oppress people with multiple (dis)advantageous conditions. This study examined intersectional inequity in knowledge, attitudes, and testing related to HIV among adults aged 15 to 49 years in Ethiopia. This study used nationally representative 2016 Ethiopian Demographic Health Survey data. The sample size was 27,261 for knowledge about HIV/AIDS and 25,542 for attitude towards people living with HIV and HIV testing. Triple (dis)advantage groups were based on wealth status, education status, and residence. The triple advantages variables specifically are urban residents, the educated, and those who belong to households of high wealth status, while the triple disadvantages are rural residents, the uneducated, and those who live in poor household wealth rank. A multilevel logistic regression analysis was employed. Adjusted odds ratios (aOR) and confidence intervals (CI) with a P-value ≤ 0.05 were considered statistically significant. Based on descriptive analysis, 27.9% (95% CI: 26.5%, 29.3%) of adults had comprehensive knowledge about HIV/AIDS, 39.8% (95% CI: 37.6, 41.9%) exhibited accepting attitude towards people living with HIV, and 20.4% (95% CI: 19.1%, 21.8%) undergo HIV testing. Comprehensive knowledge about HIV/AIDS, accepting attitude towards people living with HIV, and HIV testing was 47.0%, 75.7%, and 36.1% among those with triple advantages, and 13.9%, 16.0% and 8.7% among those with triple non-advantages, respectively. The odds of having comprehensive knowledge about HIV/AIDS, accepting attitude towards people living with HIV, and HIV testing were about three (aOR = 3.4; 95% CI: 2.76 to 4.21), seven (aOR = 7.3; 95% CI = 5.79 to 9.24) and five (aOR = 4.7; 95% CI:3.60 to 6.10) times higher for triple forms of advantage than triple disadvantages, respectively. The findings of this study imply that Ethiopia will not achieve the proposed targets for HIV/AIDS services unless it prioritises individuals who live under multiple disadvantaged conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Endalamaw et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Equitable service provision and coverage are important responses to end the threat of the HIV/AIDS pandemic. Understanding inequity supports policies and programmes to deliver tailored interventions. There is continuous evidence generation on inequity in HIV/AIDS services. However, there was a lack of evidence on the global picture of inequity in behavioural and biomedical services related to HIV/AIDS. This systematic review assessed inequities in knowledge, attitude, HIV testing, and ART coverage across individual-level social groups and multiple (dis)advantage categories., Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline, with a PROSPERO registration number CRD42024521247. The risk of bias was assessed by using Hoy et al's and Joanna Brigg's quality appraisal checklists for cross-sectional quantitative and qualitative studies, respectively. The search date was from inception to the final database search date (May 29, 2023). The included articles were either quantitative or qualitative studies. We used mixed-methods approach to analyse the data from the review articles. Quantitative descriptive analysis was conducted to estimate frequency of articles published from different countries around the world. Qualitative content analysis of the findings from the original studies was conducted using the PROGRESS plus framework which stands for: place of residence, occupation or employment status, gender, religion, education status, socioeconomic status, and social capital., Results: Out of 6,029 articles that were accessed and screened, only 72 articles met the inclusion criteria. More articles on HIV-related equity in knowledge, attitude, testing, and ART were published in developed countries than in developing countries. Individuals from higher-income households had better knowledge about HIV/AIDS. Unfavourable attitudes towards people living with HIV and HIV/AIDS-associated stigma were common among women. HIV/AIDS service coverage (HIV testing or ART coverage) was higher among richer and urban residents. HIV/AIDS-associated stigma and lower levels of knowledge about HIV/AIDS were observed among multiple disadvantageous groups due to the intersection of two or more identities., Conclusions: The current review revealed that there have been disparities in HIV/AIDS services between social classes. Ending service disparity towards the global threat of HIV/AIDS demands tailored interventions based on socially disadvantaged groups (e.g., poor, rural dwellers, and women) and intersectional determinants. There is a need to understand the deep-rooted causes of inequity and the challenges that an equity-oriented system faces over time. More studies on inequity are needed, including intersectional inequity, which has been rarely studied in developing countries., (© 2024. The Author(s).)

Background: Mainstreaming HIV and AIDS across sectors is crucial to close the disparities in service provision and coverage. However, evidence has shown that certain social groups are left behind in receiving HIV/AIDS services. The objective of this study was twofold: to understand the reasons behind the existing inequities and to explore challenges of equity in HIV/AIDS services in the Amhara region of Ethiopia., Methods: Twenty-two adults (aged 26-57 years) from eighteen sectors that are mainstreaming HIV and AIDS were purposefully selected until the point of saturation and participated in a semi-structured in-depth interview conducted between January 20 and February 17, 2023. Interviewees were asked to describe their mainstreaming experiences in equitable HIV/AIDS services, reflect on the challenges and barriers that impede equitable service provision, or explain the reasons behind the existence of inequity in HIV/AIDS services. The interviews were audio recorded, transcribed, translated, and iteratively analysed, with early analysis informing subsequent interviews. An inductive-reflexive thematic analysis was conducted, whereby themes and subthemes were identified, and the relationships between subthemes and patterns were critically reviewed., Results: The challenges to equitable HIV/AIDS service provision were grouped into eight thematic areas: (1) changing contexts that shifts public and government attention to emerging diseases, war and political instability, and poverty; (2) leadership-related, such as the lack of supervision and monitoring, not politicising HIV/AIDS (not providing political attention to HIV/AIDS) and weak intersectoral collaboration; (3) financial constraints due to a random budgeting and contract interruption with non-governmental organisations (NGOs); (4) lack of resources due to scarcity and unfair distribution; (5) inadequate skilled personnel due to inadequate numbers and lack of continuous professional and career development; (6) lack of equity-related evidence-based tools and guidelines; (7) inadequate understanding of equity due to lack of training and misunderstanding, and lack of access to equity-oriented tools and guidelines; and (8) cultural norms, values, and perceptions., Conclusions: This study identified critical challenges faced in the equitable HIV/AIDS services provision. To achieve equity in HIV/AIDS services, mainstreaming sectors need to invest in mechanisms to sustain services in emergency situations; identify effective leaders to maintain collaboration, monitoring, and evaluation; institutionalise responsive budgeting and establish alternative funds to maintain non-governmental organisations initiatives; provide continuous up-to-date training and create a common evidence-sharing platform; implement proper recruitment, education, and professional development of HIV/AIDS focal persons; and promote and practice culturally safe care. It is, therefore, essential to optimise sectors that are mainstreaming HIV/AIDS and incorporate equity considerations in their strategic plans and working guidelines., (© 2024. The Author(s).)

Objective: University creates unique social environments for many young people that can result in behaviour changes that can impact sexual health-related risks and facilitate transmission of HIV. Little is known about HIV knowledge, risk, and awareness of pre-exposure prophylaxis/post-exposure prophylaxis (PrEP/PEP) among Australian university students., Methods: A 2019 online survey distributed through Queensland universities, using active recruitment/snowball sampling. Descriptive and logistical regression analysis investigated HIV knowledge/risk and PrEP/PEP awareness., Results: Of the 4,291 responses, 60.4% were 20-29 years old, 57.0% identified as heterosexual, and 31.8% were born-overseas. Mean HIV knowledge score was 9.8/12. HIV risk scores were higher among men-who-have-sex-with-men (MSM) (mean=5.2/40) compared to all other sexual behaviours (mean=3.1/40). Logistic regression indicated PrEP and PEP awareness was associated with older age (p<0.05), being non-binary/gender-diverse (p<0.05), and MSM (p<0.05). Lower odds of PrEP awareness were associated with international student status (p<0.05)., Conclusion: This study highlights the need for future health promotion targeting younger Australians at risk of HIV to increase uptake of PrEP/PEP, particularly among overseas-born young people and those ineligible for appropriate health care in Australia., Implications for Public Health: Addressing these gaps will improve sexual health outcomes for young Australians at risk of HIV and work towards virtual elimination of HIV transmission in Australia., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: HIV testing is the entry point to HIV prevention, care and treatment and needs continuous evaluation to understand whether all social groups have accessed services equally. Addressing disparities in HIV testing between social groups results in effective and efficient response against HIV prevention. Despite these benefits, there was no previous study on inequality and determinants over time in Ethiopia. Thus, the objective of this research was to examine socioeconomic inequality in individuals undertaking HIV testing over time, allowing for the identification of persistent and emerging determinants., Methods: Data sources for the current study were the 2011 and 2016 Ethiopian Demographic Health Surveys. The 2016 population health survey is the one that Ethiopia used to set national AIDS response strategies; there was no other recent survey with HIV/AIDS-related indicators in Ethiopia. The final sample size for the current study was 28,478 for the year 2011 and 25,542 for the year 2016. The concentration curve and Erreygers' concentration index were used to estimate socioeconomic inequality in HIV testing. Subsequently, decomposition analysis was performed to identify persistent and emerging contributors of socioeconomic inequality. Generalized linear regression model with the logit link function was employed to estimate the marginal effect, elasticity, Erreygers' concentration index (ECI), and absolute and percentage contributions of each covariate., Results: The concentration curve was below the line of equality over time, revealing the pro-rich inequality in HIV testing. The inequality was observed in both 2011 (ECI = 0.200) and 2016 (ECI = 0.213). A household wealth rank had the highest percentage contribution (49.2%) for inequality in HIV testing in 2011, which increased to 61.1% in 2016. Additional markers include listening to the radio (13.4% in 2011 and 12.1% in 2016), education status (8.1% in 2011 and 6.8% in 2016), and resident (-2.0% in 2011 and 6.3% in 2016). Persistent determinants of individuals undertaking HIV testing were age 20-34 years, geographic region, education status, marital status, religion, income, media exposure (listening to the radio, reading newspaper, watching television), knowledge about HIV/AIDS, and attitudes towards people living with HIV. Age between 35 and 44 years and urban residence emerged as new associated factors in 2016., Conclusions: The higher HIV testing coverage was among individuals with higher socioeconomic status in Ethiopia. Socioeconomic inequality amongst individuals undertaking HIV testing was diverging over time. Household wealth rank, mass media exposure, education status, and resident took the largest share in explaining the disparity in individuals undertaking HIV testing between the lower and higher income groups. Therefore, interventions to equalise HIV testing coverage should take account of these determinants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Endalamaw et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The public's accepting attitude toward people living with HIV is crucial in reducing HIV-related stigma and discrimination, increasing people's access to HIV service. This study examines the inequalities in accepting attitudes toward people living with HIV in Ethiopia from 2005 to 2016., Methods: This cross-sectional study was based on the 2005, 2011 and 2016 Ethiopian Demographic Health Surveys. A total of 17 075, 28 478 and 25 542 adults were included in the 2005, 2011 and 2016 surveys, respectively. Socioeconomic inequality was investigated using the concentration curve and Erreygers' concentration index (ECI), which is scaled from -1 (pro-poor) to +1 (pro-rich). The ECI was decomposed to identify the contributors to socioeconomic inequality using generalised linear regression with the logit link function., Results: Accepting attitude toward people living with HIV was 17.9% (95% CI: 16.6%, 19.3%) in 2005, which increased to 33.5% (95% CI: 31.8%, 35.3%) in 2011 and 39.6% (95% CI: 37.6%, 41.9%) in 2016. ECI was 0.342 (p<0.001), 0.436 (p<0.001) and 0.388 (p<0.001), respectively, for 2005, 2011 and 2016. The trend line illustrates socioeconomic inequality seems diverging over time, with an increasing ECI of 0.005 every year (r=0.53; p=0.642; slope=0.005)., Conclusions: The current study found that there was pro-rich inequality from 2005 to 2016. People with higher socioeconomic status had a better attitude toward people living with HIV. Comprehensive knowledge about HIV/AIDS, education status, residence, and access to electronic and paper-based media, as well as HIV testing, contribute to a better accepting attitude toward people living with HIV. It is of utmost importance for the country to enhance accepting attitude toward people living with HIV to reduce stigma and discrimination. This requires whole-system response according to the primary healthcare approach toward ending the epidemic of HIV/AIDS in the country., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Socioeconomic inequality in comprehensive knowledge about HIV/AIDS can hinder progress towards ending the epidemic threat of this disease. To address the knowledge gap, it is essential to investigate inequality in HIV/AIDS services. This study aimed to investigate socioeconomic inequality, identify contributors, and analyze the trends in inequality in comprehensive knowledge about HIV/AIDS among adults in Ethiopia. A cross-sectional study was conducted using 2005, 2011, and 2016 population-based health survey data. The sample size was 18,818 in 2005, 29,264 in 2011, and 27,261 in 2016. Socioeconomic inequality in comprehensive knowledge about HIV/AIDS was quantified by using a concentration curve and index. Subsequently, the decomposition of the concentration index was conducted using generalised linear regression with a logit link function to quantify covariates' contribution to wealth-based inequality. The Erreygers' concentration index was 0.251, 0.239, and 0.201 in 2005, 2011, and 2016, respectively. Watching television (24.2%), household wealth rank (21.4%), ever having been tested for HIV (15.3%), and education status (14.3%) took the significant share of socioeconomic inequality. The percentage contribution of watching television increased from 4.3% in 2005 to 24.2% in 2016. The household wealth rank contribution increased from 14.6% in 2005 to 21.38% in 2016. Education status contribution decreased from 16.2% to 14.3%. The percentage contribution of listening to the radio decreased from 16.9% in 2005 to -2.4% in 2016. The percentage contribution of residence decreased from 7.8% in 2005 to -0.5% in 2016. This study shows comprehensive knowledge about HIV/AIDS was concentrated among individuals with a higher socioeconomic status. Socioeconomic-related inequality in comprehensive knowledge about HIV/AIDS is woven deeply in Ethiopia, though this disparity has been decreased minimally. A combination of individual and public health approaches entangled in a societal system are crucial remedies for the general population and disadvantaged groups. This requires comprehensive interventions according to the primary health care approach., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Endalamaw et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Multiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear., Objective: To determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children., Design, Setting, and Participants: Clinical data from hospitalized children and adolescents (younger than 18 years) who were SARS-CoV-2 positive were obtained from 9 countries (Australia, Brazil, Italy, Portugal, South Africa, Switzerland, Thailand, UK, and the US) during 3 different time frames. Time frames 1 (T1), 2 (T2), and 3 (T3) were defined to represent periods of dominance by the ancestral virus, pre-Omicron VOCs, and Omicron, respectively. Age groups for analysis were younger than 6 months, 6 months to younger than 5 years, and 5 to younger than 18 years. Children with an incidental positive test result for SARS-CoV-2 were excluded., Exposures: SARS-CoV-2 hospitalization during the stipulated time frame., Main Outcomes and Measures: The severity of disease was assessed by admission to intensive care unit (ICU), the need for ventilatory support, or oxygen therapy., Results: Among 31 785 hospitalized children and adolescents, the median age was 4 (IQR 1-12) years and 16 639 were male (52.3%). In children younger than 5 years, across successive SARS-CoV-2 waves, there was a reduction in ICU admission (T3 vs T1: risk ratio [RR], 0.56; 95% CI, 0.42-0.75 [younger than 6 months]; RR, 0.61, 95% CI; 0.47-0.79 [6 months to younger than 5 years]), but not ventilatory support or oxygen therapy. In contrast, ICU admission (T3 vs T1: RR, 0.39, 95% CI, 0.32-0.48), ventilatory support (T3 vs T1: RR, 0.37; 95% CI, 0.27-0.51), and oxygen therapy (T3 vs T1: RR, 0.47; 95% CI, 0.32-0.70) decreased across SARS-CoV-2 waves in children 5 years to younger than 18 years old. The results were consistent when data were restricted to unvaccinated children., Conclusions and Relevance: This study provides valuable insights into the impact of SARS-CoV-2 VOCs on the severity of COVID-19 in hospitalized children across different age groups and countries, suggesting that while ICU admissions decreased across the pandemic in all age groups, ventilatory and oxygen support generally did not decrease over time in children aged younger than 5 years. These findings highlight the importance of considering different pediatric age groups when assessing disease severity in COVID-19.

Background: Post-exposure prophylaxis (PEP) offers protection from HIV after condomless sex, but is not widely available in a timely manner in east, central, southern, and west Africa. To inform the potential pilot implementation of such an approach, we modelled the effect and cost-effectiveness of making PEP consisting of tenofovir, lamivudine, and dolutegravir (TLD) freely and locally available in communities without prescription, with the aim of enabling PEP use within 24 h of condomless sex. Free community availability of TLD (referred to as community TLD) might also result in some use of TLD as pre-exposure prophylaxis (PrEP) and as antiretroviral therapy for people living with HIV., Methods: Using an existing individual-based model (HIV Synthesis), we explicitly modelled the potential positive and negative effects of community TLD. Through the sampling of parameter values we created 1000 setting-scenarios, reflecting the uncertainty in assumptions and a range of settings similar to those seen in east, central, southern, and west Africa (with a median HIV prevalence of 14·8% in women and 8·1% in men). For each setting scenario, we considered the effects of community TLD. TLD PEP was assumed to have at least 90% efficacy in preventing HIV infection after condomless sex with a person living with HIV., Findings: The modelled effects of community TLD availability based on an assumed high uptake of TLD resulted in a mean reduction in incidence of 31% (90% range over setting scenarios, 6% increase to 57% decrease) over 20 years, with an HIV incidence reduction over 50 years in 91% of the 1000 setting scenarios, deaths averted in 55% of scenarios, reduction in costs in 92% of scenarios, and disability-adjusted life-years averted in 64% of scenarios with community TLD. Community TLD was cost-effective in 90% of setting scenarios and cost-saving (with disability-adjusted life-years averted) in 58% of scenarios. When only examining setting scenarios in which there was lower uptake of community TLD, community TLD is cost-effective in 92% of setting scenarios., Interpretation: The introduction of community TLD, enabling greater PEP access, is a promising approach to consider further in pilot implementation projects., Funding: Bill & Melinda Gates Foundation to the HIV Modelling Consortium., Competing Interests: Declaration of interests ANP reports a research grant from the Bill & Melinda Gates Foundation for the current work; and grants from Wellcome, the National Institutes for Health, and European Commission outside this work. FC reports grants from the Wellcome Trust, the Bill & Melinda Gates Foundation, the Medical Research Council, the National Institute for Mental Health, UNICEF, and UNAIDS to support travel for expert panel meetings; being a board member for UK Research and Innovation Global Health Research Board and African Research Leaders Fellowship Schemes; and being a member on a WHO Expert Panel. LB-M reports a research grant from Bill & Melinda Gates Foundation for the current work. VC reports grants from UK Research Institute, the National Institute for Mental Health, United States Agency for International Development, Medical Research Council, and the Bill & Melinda Gates Foundation. JRH reports grants from the Bill & Melinda Gates Foundation and Wellcome and consulting fees from Gavi. This Article was written by CG in her capacity as a US Government employee, but the views expressed in this paper do not represent those of the Department of State or the Centers for Disease Control and Prevention. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Human T-cell leukaemia virus type 1 (HTLV-1), an STI, is reported to be highly prevalent in Indigenous communities in Central Australia. HTLV-1 is an incurable, chronic infection which can cause Adult T-cell leukaemia/lymphoma (ATL). ATL is associated with high morbidity and mortality, with limited treatment options. We studied the prevalence of HTLV-1 and ATL in the state of Queensland, Australia., Methods: Serum samples stored at healthcare services in Brisbane, Townsville and Cairns and at haemodialysis units in Brisbane (2018-2019) were screened for HTLV-1/2 antibodies using the Abbott ARCHITECT chemiluminescent microparticle immunoassay (CMIA) for antibodies against gp46-I, gp46-II and GD21 (Abbott CMIA, ARCHITECT). Reactive samples were confirmed through Western blot. Pooled Australian National Cancer Registry surveillance data reporting on cases coded for ATL (2004-2015) were analysed., Results: Two out of 2000 hospital and health services samples were confirmed HTLV-1-positive (0.1%, 95% CI 0.02% to 0.4%), both in older women, one Indigenous and one non-Indigenous. All 540 haemodialysis samples tested negative for HTLV. All samples were HTLV-2-negative. Ten out of 42 (24.8%) reported cases of ATL in Australia were from Queensland (crude incidence rate 0.025/100 000; 95% CI 0.011 to 0.045); most cases were seen in adult men of non-Indigenous origin. Nineteen deaths due to ATL were recorded in Australia., Conclusion: We confirm that HTLV-1 and ATL were detected in Queensland in Indigenous and non-Indigenous people. These results highlight the need for HTLV-1 prevalence studies in populations at risk of STIs to allow the implementation of focused public health sexual and mother-to-child transmission prevention strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Universal health coverage is essential for the progress to end threats of the acquired immunodeficiency syndrome epidemic. The current review assesses the publication rate, strategies and barriers for antiretroviral therapy (ART) coverage, equity, quality of care, and financial protection. We searched Web of Science, PubMed, and Google Scholar. Of the available articles, 43.13% were on ART coverage, 40.28% were on financial protection, 10.43% were on quality of care, and 6.16% were on equity. A lack of ART, fear of unwanted disclosure, lack of transportation, unaffordable health care costs, long waiting time to receive care, and poverty were barriers to ART coverage. Catastrophic health care costs were higher among individuals who were living in rural settings, walked greater distances to reach health care institutions, had a lower socioeconomic status, and were immunocompromised. There were challenges to the provision of quality of care, including health care providers' inadequate salary, high workload and inadequate health workforce, inappropriate infrastructure, lack of training opportunities, unclear division of responsibility, and the presence of strict auditing. In conclusion, ART coverage was below the global average, and key populations were disproportionally less covered with ART in most countries. Huge catastrophic health expenditures were observed. UHC contexts of ART will be improved by reaching people with poor socioeconomic status, delivering appropriate services, establishing a proper health workforce and service stewardship.

Patient satisfaction is a critical component of quality of care assessment in the pursuit of universal health coverage to end the tuberculosis epidemic and other diseases. This study aimed to review the level of satisfaction of tuberculosis patients and related factors. Articles were accessed from Web of Science, EMBASE, PubMed and Google Scholar. Twenty-six papers fulfilled the eligibility criteria from 13 countries. The percentage of satisfied tuberculosis patients ranged from 53.5% to 97.0% in the five African countries, 67.8 to 97.2% in India, South-East Asia, 82.0% in Pakistan, East-Mediterranean and 92.9% in Armenia, the European region. Accessibility, healthcare cost, treatment duration and taking supervised-directly observed treatment were healthcare service-related determinants. Technical competency, interpersonal relationships, confidentiality, time spent with healthcare providers, time spent waiting for care and counselling and health education were health worker-related determinants. Patient-related variables that determine satisfaction were gender, age, ethnicity, place of residence, marital status, educational status, income and health status. Developing and/or approaching an internationally-agreed tool to measure tuberculosis patient satisfaction in healthcare settings will improve the availability of high-quality and comparable data to verify actual variation across and within a country. A multidimensional approach considering clients, health workers and healthcare settings is required to holistically address satisfaction issues of tuberculosis patients to gradually realise universal health coverage., (© 2022 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

Background: The progress of Universal health coverage (UHC) is measured using tracer indicators of key interventions, which have been implemented in healthcare system. UHC is about population, comprehensive health services and financial coverage for equitable quality services and health outcome. There is dearth of evidence about the extent of the universality of UHC in terms of types of health services, its integrated definition (dimensions) and tracer indicators utilized in the measurement of UHC. Therefore, we mapped the existing literature to assess universality of UHC and summarize the challenges towards UHC., Methods: The checklist Preferred Reporting Items for Systematic reviews and Meta-analysis extension for Scoping Reviews was used. A systematic search was carried out in the Web of Science and PubMed databases. Hand searches were also conducted to find articles from Google Scholar, the World Bank Library, the World Health Organization Library, the United Nations Digital Library Collections, and Google. Article search date was between 20 October 2021 and 12 November 2021 and the most recent update was done on 03 March 2022. Articles on UHC coverage, financial risk protection, quality of care, and inequity were included. The Population, Concept, and Context framework was used to determine the eligibility of research questions. A stepwise approach was used to identify and select relevant studies, conduct data charting, collation and summarization, as well as report results. Simple descriptive statistics and narrative synthesis were used to present the findings., Results: Forty-seven papers were included in the final review. One-fourth of the articles (25.5%) were from the African region and 29.8% were from lower-middle-income countries. More than half of the articles (54.1%) followed a quantitative research approach. Of included articles, coverage was assessed by 53.2% of articles; financial risk protection by 27.7%, inequity by 25.5% and quality by 6.4% of the articles as the main research objectives or mentioned in result section. Most (42.5%) of articles investigated health promotion and 2.1% palliation and rehabilitation services. Policy and healthcare level and cross-cutting barriers of UHC were identified. Financing, leadership/governance, inequity, weak regulation and supervision mechanism, and poverty were most repeated policy level barriers. Poor quality health services and inadequate health workforce were the common barriers from health sector challenges. Lack of common understanding on UHC was frequently mentioned as a cross-cutting barrier., Conclusions: The review showed that majority of the articles were from the African region. Methodologically, quantitative research design was more frequently used to investigate UHC. Palliation and rehabilitation health care services need attention in the monitoring and evaluation of UHC progress. It is also noteworthy to focus on quality and inequity of health services. The study implies that urgent action on the identified policy, health system and cross-cutting barriers is required to achieve UHC., Competing Interests: Authors declared no conflict of interest.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic takes variable shapes and forms in different regions and countries. This variability is explained by several factors, including the governance of the epidemic. We aimed to identify the key attributes of governance in response to the COVID-19 pandemic and gain lessons for an effective response to public health emergencies., Methods: We employed a mixed-methods design. We mapped the attributes of governance from well-established governance frameworks. A negative binomial regression was conducted to identify the effect of the established governance measures on the epidemiology of the COVID-19 pandemic. We used publicly available data on COVID-19 cases and deaths in countries around the world. Document review was conducted to identify the key approaches and attributes of governance during the pre-vaccine era of the response to the COVID-19 pandemic. We conducted a thematic analysis to identify key attributes for effective governance., Results: The established governance measures, including generation of intelligence, strategic direction, regulation, partnership, accountability, transparency, rule of law, control of corruption, responsiveness, effectiveness, efficiency, equity, ethics, and inclusiveness, are necessary but not sufficient to effectively respond to and contain the COVID-19 pandemic. Additional attributes of national governance were identified: 1) agile, adaptive, and transformative governance; 2) collective (collaborative, inclusive, cooperative, accountable, and transparent) governance; 3) multi-level governance; 4) smart and ethical governance: sensible, pragmatic, evidence-based, political, learner, and ethical., Conclusions: The current governance frameworks and their attributes are not adequate to contain the COVID-19 pandemic. We argue that countries need agile, adaptable, and transformational, collaborative, multi-level, smart and ethical governance to effectively respond to emerging and re-emerging public health threats. In addition, an effective response to public health emergencies depends not only on national governance but also on global governance. Hence, global health governance should be urgently renewed through a paradigm shift towards universal health coverage and health security to all populations and in all countries. This requires enhanced and consistent global health diplomacy based on knowledge, solidarity, and negotiation., Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interests Form (available upon request from the corresponding author) and declare no conflicts of interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Background: The pandemic of Coronavirus Disease 2019 (COVID-19) is a timely reminder of the nature and impact of Public Health Emergencies of International Concern. As of 12 January 2022, there were over 314 million cases and over 5.5 million deaths notified since the start of the pandemic. The COVID-19 pandemic takes variable shapes and forms, in terms of cases and deaths, in different regions and countries of the world. The objective of this study is to analyse the variable expression of COVID-19 pandemic so that lessons can be learned towards an effective public health emergency response., Methods: We conducted a mixed-methods study to understand the heterogeneity of cases and deaths due to the COVID-19 pandemic. Correlation analysis and scatter plot were employed for the quantitative data. We used Spearman's correlation analysis to determine relationship strength between cases and deaths and socio-economic and health systems. We organized qualitative information from the literature and conducted a thematic analysis to recognize patterns of cases and deaths and explain the findings from the quantitative data., Results: We have found that regions and countries with high human development index have higher cases and deaths per million population due to COVID-19. This is due to international connectedness and mobility of their population related to trade and tourism, and their vulnerability related to older populations and higher rates of non-communicable diseases. We have also identified that the burden of the pandemic is also variable among high- and middle-income countries due to differences in the governance of the pandemic, fragmentation of health systems, and socio-economic inequities., Conclusion: The COVID-19 pandemic demonstrates that every country remains vulnerable to public health emergencies. The aspiration towards a healthier and safer society requires that countries develop and implement a coherent and context-specific national strategy, improve governance of public health emergencies, build the capacity of their (public) health systems, minimize fragmentation, and tackle upstream structural issues, including socio-economic inequities. This is possible through a primary health care approach, which ensures provision of universal and equitable promotive, preventive and curative services, through whole-of-government and whole-of-society approaches., (© 2022. The Author(s).)

HIV self-testing (HIVST) introduces opportunities for screening in non-conventional settings, and addresses known testing barriers. This study involved the development and evaluation of a free online HIVST dissemination service hosted by a peer-led, community-based organisation with on-site, peer-facilitated HIV testing, and established referral and support programs for people newly diagnosed with HIV to determine whether this model was feasible and acceptable for engaging MSM, particularly among infrequent and naive HIV-testers, or those living in remote and rural areas. Between December 2016 and April 2018, 927 kits were ordered by 794 individuals, the majority of whom were men who have sex with men (MSM) (62%; 494), having condomless sex (50%; 392), or living outside a major city (38%; 305). Very few (5%; 39) sought the available pre-test peer contact, despite 45% (353) being naive HIV-testers. This study demonstrates that online HIVST dissemination is acceptable and feasible for engaging at-risk suboptimal testers, including those unwilling to test elsewhere (19%; 47/225). With half (50%; 403) unwilling to buy a kit, our study suggests that HIVST will need to be subsidized (cost-neutral to users) to enhance population coverage and access.

Competing Interests: Competing interests: None declared.

The third Sustainable Development Goal (SDG-3) has a target to end the epidemic of HIV/AIDS by 2030 (Project 2030). This will be achieved when the number of new HIV infections and 'AIDS-related deaths' decline by 90% between 2010 and 2030. So far, the rate of drop in AIDS-related deaths is on track, whereas the rate of drop in new HIV infections is off track to achieve Project 2030. Even if Project 2030 was achieved, HIV would be an endemic health problem. Hence, HIV prevention and control programmes cannot close down for the foreseeable future. This rather demands a paradigm shift from a fully vertical to an integrated health systems response that provides services according to disease burden towards universal health coverage. This will ensure the sustainability of HIV services in the post-2030 era. These all entail unrelenting political commitment, and increased and sustainable funding from both national and global sources., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

HIV associated tuberculosis (TB) morbidity and mortality is a major concern in sub-Saharan Africa. Understanding the level of HIV infection among TB patients is vital for adequate response. We conducted a systematic review and meta-analysis to estimate the prevalence of HIV in TB patients in sub-Saharan Africa. We searched PubMed, EMBASE, Web of Science and CINAHL databases. A meta-analysis with a random-effects model was performed. Potential sources of heterogeneity in the prevalence estimates were explored using meta-regression analysis. We identified 68 studies that collectively included 62,969 TB patients between 1990 and 2017. The overall estimate of HIV prevalence in TB patients was 31.8% (95% CI 27.8-36.1). There was substantial heterogeneity in the prevalence estimates in Southern, Central, Eastern, and Western sub-Saharan Africa regions (43.7, 41.3, 31.1 and 25.5%, respectively). We noted an apparent reduction in the estimate from 33.7% (95% CI 27.6-40.4) in the period before 2000 to 25.7% (95% CI 17.6-336.6) in the period after 2010. The Eastern and Southern sub-Saharan Africa region had higher prevalence [34.4% (95% CI 29.3-34.4)] than the Western and Central region [27.3% (95% CI 21.6-33.8)]. The prevalence of HIV in TB patients has declined over time in sub-Saharan Africa. We argue that this is due to strengthened HIV prevention and control response and enhanced TB/HIV collaborative activities. Countries and regions with high burdens of HIV and TB should strengthen and sustain efforts in order to achieve the goal of ending both HIV and TB epidemics in line with the Sustainable Development Goals.

Background: Ethiopia has adopted the global plan to end the epidemic of HIV/AIDS. The aim of this study was to assess the progress made towards achieving this plan., Methods: A review and analysis of national population-based surveys, surveillance, and routine programme data was executed. The data analysis was conducted using Excel 2016 and Stata 14 (StataCorp LP, College Station, TX, USA)., Results: Between 2011 and 2016, the number of HIV-related deaths dropped by 58%, while that of new HIV infections dropped by only 6%. Discriminatory attitudes declined significantly from 77.9% (95% confidence interval (CI) 77.3-78.4%) in 2011 to 41.5% (95% CI 40.6-42.4%) in 2016. Around 79% of adult people living with HIV (PLHIV) were aware of their HIV status; 90% of PLHIV who were aware of their HIV status were taking antiretroviral treatment (ART) and 88% of adult PLHIV on ART had viral suppression in 2016. The proportion of people aged 15-49 years who had ever been tested for HIV and had received results increased from 39.8% (95% CI 39.2-40.4%) in 2011 to 44.8% (95% CI 44.2-45.4%) in 2016. This proportion was very low among children below age 15 years at only 6.2% (95% CI 5.9-6.5%). Among regions, HIV testing coverage varied from 13% to 72%. Female sex workers had lower coverage for HIV testing (31%) and ART (70%) than the national average in the adult population. International funding for HIV dropped from more than US$ 1.3 billion in 2010-2012 to less than US$ 800 million in 2016-2018., Conclusions: Ethiopia is on track to achieve the targets for HIV testing, ART, viral suppression, and AIDS-related deaths, but not for reductions in new HIV infections, discriminatory attitudes, and equity. Ending the epidemic of HIV/AIDS requires a combined response, including prevention and treatment, tailored to key populations and locations, as well as increased funding., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Q fever caused by the gram negative bacteria, Coxiella burnetii, is an occupational hazard for those who live and work in rural settings and those who are in contact with animals, especially abattoir and slaughterhouse workers. Australia is the only country to register a vaccine to prevent Q fever (Q-vax®, Seqirus, Australia) that is used in high risk populations. Seroprevalence studies conducted to determine the burden of Q fever ( C. burnetii infection) in different settings have demonstrated high levels of heterogeneity with estimates of the percent positive ranging from 30% to 70%. There is a need for a more systematic evaluation of the findings of these studies in order to provide summary estimates of the seroprevalence in different settings. We searched for published articles using PubMed, MEDLINE-EMBASE, and Scopus databases using search terms obtained from an initial review of published reports of recent Q fever outbreaks. Data on the seroprevalence of C. burnetii infection (Q fever) was extracted from the selected studies and a random effects meta-analysis was performed with stratification by outbreak status, year, country and serological techniques used. Results were visualised with a forest plot with 95% CI and measures of heterogeneity ( I 2 ) for the random effects model. A total of 19 articles that met the search criteria were included. The reported seroprevalence rate ranged from 4.7% to 91.7% among abattoir and slaughterhouse workers. No inter-group heterogeneity was observed (p = 0.956), supporting the pooling of all studies into one pooled measure. The pooled estimate of seropositivity for C. burnetii infection in people working in abattoirs and slaughterhouses was 26% (95% CI: 18-35%) regardless of the evidence of an "outbreak", the time of year or country. Seropositivity for C burnetii was independent of a person's age and years of occupational experience. Within abattoirs and slaughterhouses, slaughtering of cattle, sheep and goats are the most important risk factors associated with seropositivity and for those who showed over symptoms upon infection. We recommend that vaccination programmes are directed towards people employed in the meat processing industry to mitigate the significant health and economic impacts of Q fever.

Background: Ethiopia is one of the countries which has scaled up antiretroviral treatment (ART) over the past decade. This study reviews the performance of the ART program in Ethiopia during the past decade, and identifies successes and weaknesses toward ending AIDS in the country., Methods: A review and synthesis of data was conducted using multiple data sources: reports from all health facilities in Ethiopia to the Federal Ministry of Health, HIV/AIDS estimates and projections, and retrospective cohort and cross-sectional studies conducted between 2005/6 and 2014/15., Findings: The ART program has been successful over several critical areas: (1) ART coverage improved from 4% to 54%; (2) the median CD4 count/mm 3 at the time of ART initiation increased from 125 in 2005/6 to 231 in 2012/13; (3) retention in care after 12 months on ART has increased from 82% to 92%. In spite of these successes, important challenges also remain: (1) ART coverage is not equitable: among regions (5.6%-93%), between children (25%) and adults (60%), and between female (54%) and male patients (69%); (2) retention in care is variable among regions (83%-94%); and, (3) the shift to second-line ART is slow and low (0·58%)., Interpretation: The findings suggest that the ART program should sustain the successes and reflect on the shortcomings toward the goal of ending AIDS. It is important to capitalize on and calibrate the interventions and approaches utilized to scale up ART in the past. Analysis of the treatment cascade, in order to pinpoint the gaps and identify appropriate solutions, is commendable in this regard., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: We investigated the prevalence, incidence and predictors of new peripheral neuropathy episodes in previously untreated, symptomatic HIV-infected Ugandan/Zimbabwean adults initiating zidovudine-based antiretroviral therapy (ART)., Design: An open-label, multicentre, randomized trial., Methods: Peripheral neuropathy was self-reported at 12-weekly clinic visits. Cox regression models (excluding participants reporting preexisting peripheral neuropathy at ART initiation), considered sex; pre-ART WHO stage, age and CD4(+) cell count; CD4(+) cell count versus no CD4(+) cell count monitoring; and time-updated CD4(+) cell count, weight and use of stavudine, isoniazid and didanosine., Results: Four hundred and twenty-one out of 3316(13%) patients reported preexisting peripheral neuropathy at ART initiation. Median (interquartile range, IQR) follow-up in 2895 participants without preexisting peripheral neuropathy was 4.9 (4.7-5.4) years. Three hundred and fifty-four (12%) took stavudine as first-line substitution and 518 (18%) took isoniazid during follow-up. Two hundred and ninety (11%) participants developed a new peripheral neuropathy episode, an incidence of 2.12 per 100 person-years. Eighteen (0.1%) had a grade 3/4 episode. Independent predictors of peripheral neuropathy were current stavudine use [adjusted hazard ratio (a)HR 4.16 (95% confidence interval, 95% CI 3.06-5.66], current isoniazid use [aHR 1.59 (95% CI 1.02-2.47)] and current didanosine use [aHR 1.60 (95% CI 1.19-2.14)]. Higher risks were independently associated with higher pre-ART weight [aHR (per+5 kg) 1.07 (95% CI 1.01-1.13)] and older age aHR (per 10 years older) 1.29 (95% CI 1.12-1.49), but there was no significant effect of sex (P = 0.13), pre-ART CD4(+) cell count (P = 0.91) or CD4(+) cell count monitoring (P = 0.73)., Conclusion: Current stavudine, didanosine or isoniazid use continue to increase peripheral neuropathy risks, as does older age and weight at ART initiation; however, we found no evidence of increased risk in women in contrast to previous studies. The incidence of peripheral neuropathy may now be lower in ART programmes, as stavudine and didanosine are no longer recommended. All patients receiving isoniazid, either as part of antituberculosis (TB) chemotherapy or TB-preventive therapy, should receive pyridoxine as recommended in national guidelines.

Background: Increasing numbers of HIV-infected patients in sub-Saharan Africa are exposed to antiretroviral therapy (ART), but there are few data on lipid changes on first-line ART, and even fewer on second-line., Methods: DART was a randomized trial comparing monitoring strategies in Ugandan/Zimbabwean adults initiating first-line ART and switching to second-line at clinical/immunological failure. We evaluated fasting lipid profiles at second-line initiation and ≥48 weeks subsequently in stored samples from Zimbabwean patients switching before 18 September 2006., Results: Of 91 patients switched to second-line ART, 65(73%) had fasting samples at switch and ≥48 weeks, 14(15%) died or were lost <48 weeks, 10(11%) interrupted ART for >14 days and 2(2%) had no samples available. 56/65(86%) received ZDV/d4T + 3TC + TDF first-line, 6(9%) ZDV/d4T + 3TC + NVP and 3(5%) ZDV + 3TC with TDF and NVP. Initial second-line regimens were LPV/r + NNRTI in 27(41%), LPV/r + NNRTI + ddI in 33(50%) and LPV/r + TDF + ddI/3TC/ZDV in 6(9%). At second-line initiation median (IQR) TC, LDL-C, HDL-C and TG (mmol/L) were 3.3(2.8-4.0), 1.7(1.3-2.2), 0.7(0.6-0.9) and 1.1(0.8-1.9) respectively. Levels were significantly increased 48 weeks later, by mean (SE) +2.0(0.1), +1.1(0.1), +0.5(0.05) and +0.4(0.2) respectively (p < 0.001; TG p = 0.01). 3% at switch vs 25% 48 weeks later had TC >5.2 mmol/L; 3% vs 25% LDL-C >3.4 mmol/L and 91% vs 41% HDL-C <1.1 mmol/L (p < 0.001). Similar proportions had TG >1.8 mmol/L (0 vs 3%) and TC/HDL-C ≥5 (40% vs 33%) (p > 0.15)., Conclusion: Modest lipid elevations were observed in African patients on predominantly LPV/r + NNRTI-based second-line regimens. Routine lipid monitoring during second-line ART regimens may not be warranted in this setting but individual cardiovascular risk assessment should guide practice.

Objective: To assess the psychometric performance of using standard gamble (SG), time trade-off (TTO) and visual analogue scale (VAS) in the evaluation of three predetermined HIV/AIDS health states in HIV-infected Ugandans, for use in cost-effectiveness analyses., Methods: We recruited participants with CD4 cells <200/microl from the Development of AntiRetroviral Therapy in Africa (DART) trial cohort [randomized trial evaluating antiretroviral therapy (ART) management strategies] in Uganda, before they initiated ART (n = 276). A comparison group of ART-naive HIV-infected individuals was recruited from the Entebbe Cohort study (n = 159). Participants were interviewed and asked to rate his/her own health state using VAS; rank and evaluate HIV/AIDS predetermined health states using TTO and SG relative to an improved health state. Tools were tested for psychometrical properties., Results: Women constituted 64% and 76% of the DART and Entebbe Cohorts. Mean age was 36.5 and 36.7 years, respectively. Participants could discriminate between predetermined HIV/AIDS health states. Deterioration in health status was associated with a reduction in rating scores (VAS), increased willingness to give up time (TTO) and acceptance of increased risk (SG) to achieve a better health state, independent of the participant's actual health state, as measured by CD4 cell counts., Conclusion: VAS, TTO and SG have good psychometric properties, making them good candidates for use in resource-constrained settings. Further research in a wider population is necessary to generate an evidence base with which to inform resource allocation decisions.

WHO has proposed a public-health approach to antiretroviral therapy (ART) to enable scaling-up access to treatment for HIV-positive people in developing countries, recognising that the western model of specialist physician management and advanced laboratory monitoring is not feasible in resource-poor settings. In this approach, standardised simplified treatment protocols and decentralised service delivery enable treatment to be delivered to large numbers of HIV-positive adults and children through the public and private sector. Simplified tools and approaches to clinical decision-making, centred on the "four Ss"--when to: start drug treatment; substitute for toxicity; switch after treatment failure; and stop--enable lower level health-care workers to deliver care. Simple limited formularies have driven large-scale production of fixed-dose combinations for first-line treatment for adults and lowered prices, but to ensure access to ART in the poorest countries, the care and drugs should be given free at point of service delivery. Population-based surveillance for acquired and transmitted resistance is needed to address concerns that switching regimens on the basis of clinical criteria for failure alone could lead to widespread emergence of drug-resistant virus strains. The integrated management of adult or childhood illness (IMAI/IMCI) facilitates decentralised implementation that is integrated within existing health systems. Simplified operational guidelines, tools, and training materials enable clinical teams in primary-care and second-level facilities to deliver HIV prevention, HIV care, and ART, and to use a standardised patient-tracking system.

Aims: To investigate the existence of national adult antiretroviral therapy (ART) guidelines in 43 World Health Organization (WHO) '3 by 5' focus countries and compare their content with the 2003 WHO ART guidelines., Methods: Questionnaires covered initiation of ART, selection of first or second-line ART, monitoring treatment response and toxicity and dissemination of national guidelines. Weighted concordance scores were created and country scores correlated with national indicators and WHO recommendations., Results: Thirty-nine (91%) countries returned questionnaires, three of which had no national ART guidelines. Of the 36, 16 (44%) recommended to start ART based on WHO clinical staging criteria and CD4 cell count or T-lymphocyte count, 12 (33%) WHO clinical staging criteria and CD4 cell count, four (11%) only CD4 cell counts. 35 (97%) recommended a standard first-line regimen and 24 (67%) preferred stavudine + lamivudine + nevirapine; 33 (92%) recommended second-line regimens, and 24 (60%) preferred abacavir + didanosine + lopinavir/ritonavir. Thirty-one (94%) recommended CD4 cell count, possibly combined with other indicators, to monitor ART. Concordance scores were higher in countries with lower health expenditure per capita (P = 0.009) and lower GDP per capita (P < 0.03). Median concordance scores for starting ART was 100 [interquartile range (IQR), 67 to 100]; first line therapy, 70 (IQR, 60 to 80); second-line regimens, 45 (IQR, 27 to 55) and for laboratory investigations, 80 (IQR, 80 to 100)., Conclusions: Most countries had developed national ART guidelines as part of a comprehensive national HIV program. Concordance with WHO recommendations was strong on starting first-line ART regimens and routine monitoring but lower for second-line recommendations.

Background: Adults with dual tuberculosis (TB) and HIV infection have a poor outcome. Studies in West Africa suggest that cotrimoxazole prophylaxis may reduce this mortality., Objective: To evaluate the effectiveness of cotrimoxazole in reducing mortality in adults with active TB, irrespective of HIV status, in a high prevalence setting., Design: Cohort study using historical controls., Methods: Adults treated for TB between 1998 and 2000 were traced and vital status at 6 months ascertained (2004: control group). All adults starting treatment for TB between June 2001 and June 2002 were offered cotrimoxazole prophylaxis 960 mg once daily for 6 months during TB treatment irrespective of HIV status (1321: intervention group). Mortality, adverse reactions and adherence were compared between intervention and control groups., Results: HIV seroprevalence in patients with TB at the start of the intervention was estimated to be 78%. Mortality at 6 months was 29% lower in the group given cotrimoxazole than in the control group. The number needed to treat to prevent one death during the period of TB treatment was 24. The benefit was seen across all types of TB but was only evident in new patients; patients being retreated had similar outcomes in both groups. Adverse events were infrequent and minor, with only two participants having treatment stopped for this reason., Conclusion: Cotrimoxazole prophylaxis for all adults with TB, irrespective of HIV status, in an area of high HIV seroprevalence may be a feasible, safe and effective way to reduce mortality for the duration of treatment.

Identifying correlates of immunity or susceptibility to disease promotes understanding of pathogenesis and development of diagnostic tools, treatments, and vaccines. There is evidence that type 1 cytokine responses are associated with protection against tuberculosis, and suppression of type 1, or switching to type 2 responses, with susceptibility, but this has not been studied prospectively. We studied a cohort of 631 HIV-1-infected Ugandan adults. At enrollment we performed whole blood cultures for type 1 (interferon [IFN]-gamma, interleukin [IL]-2) and type 2/immunosuppressive (IL-5, IL-10) responses to mycobacterial antigens (purified protein derivative [PPD] and culture filtrate proteins [CFP]). The incidence of tuberculosis was not associated with IFN-gamma responses, but was higher among participants with IL-2 responses (adjusted rate ratios [RR]: PPD 3.48; CFP 3.99; P < 0.001). For tuberculin skin test-positive participants, high incidence was also associated with an IL-10 response to PPD (adjusted RR 6.24, P = 0.03); for those with a BCG scar, high incidence was associated with positive IL-5 responses (adjusted RRs: PPD 3.64, P = 0.006; CFP 3.44, P = 0.04). The association with IL-2 production may reflect a response to tuberculous infection or to activating disease; the associations with IL-10 and IL-5 are in keeping with the expected role of immunosuppressive or type 2 cytokines.

23-Valent pneumococcal polysaccharide vaccine was previously reported to be ineffective in HIV-infected Ugandan adults. Prolonged follow-up of trial participants confirmed persistent excess of all-cause pneumonia in vaccine recipients [hazard ratio (HR) 1.6; 95% confidence interval (CI) 1.0-2.4], but surprisingly a survival advantage favouring vaccination (HR 0.84; CI 0.7-1.0). An explanation for the improvement in survival in the face of excess morbid events is lacking; a role for vaccine in HIV care in Africa remains unlikely.

Non-typhoidal salmonella (NTS) bacteraemia is a common, recurrent illness in HIV-infected African adults. We aimed to describe the presentation and outcome of NTS bacteraemia, the pattern of recurrence, and to determine whether recurrence results from re-infection or recrudescence. 100 consecutive adult inpatients with NTS bacteraemia in Blantyre, Malawi were treated with chloramphenicol (500mg qid for 14 days). Survivors were prospectively followed to detect bacteraemic recurrence. Index and recurrent isolates were typed by antibiogram, pulsed field gel electrophoresis and plasmid analysis to distinguish recrudescence from re-infection. Inpatient mortality was 47%, and 1-year mortality was 77%. 77/78 cases were HIV positive. Anaemia was associated with inpatient death, and several features of AIDS were associated with poor outpatient survival. Among survivors, 43% (19/44) had a first recurrence of NTS bacteraemia at 23-186 days. Among these, 26% (5/19) developed multiple recurrences up to 245 days. No recurrence was seen after 245 days, despite follow-up for up to 609 days (median 214). Suppurative infections were not found at presentation, and were only seen twice at recurrence. Index and recurrent paired isolates were identical by phenotyping and genotyping, consistent with recrudescence, rather than re-infection. NTS bacteraemia has a high mortality (47%) and recurrence rate (43%) in HIV-infected African adults. Recurrence is caused by recrudescence rather than re-infection. Since focal infections were rarely found, recrudescence may often be a consequence of intracellular tissue sequestration. There is an urgent need for improved primary treatment and secondary prophylaxis in Africa.

The CD45 antigen is essential for normal antigen receptor-mediated signalling in lymphocytes, and different patterns of splicing of CD45 are associated with distinct functions in lymphocytes. Abnormal CD45 splicing has been recognized in humans, caused by a C77G transversion in the gene encoding CD45 (PTPRC). Recently the C77G polymorphism has been associated with multiple sclerosis and increased susceptibility to HIV-1 infection. These studies suggest that the regulation of CD45 splicing may be critical for the proper function of the immune system. Because of these data we examined the frequency of the C77G allele in African and Asian populations from countries with high or low prevalence of HIV infection. Here we report that the variant CD45 C77G allele is absent in African populations. We further show that populations living in the Pamir mountains of Central Asia have a very high prevalence of the C77G variant.