The Trends and Risk Factors of AIDS-Defining Cancers and Non-AIDS-Defining Cancers in Adults Living with and without HIV: A Narrative Review.

Background: People living with HIV (PLHIV) are at a high-risk of developing AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs). This review is aimed at exploring available evidence regarding the trends of ADCs and NADCs and the associated risk factors among adult PLHIV. Methods: We conducted a comprehensive search of PubMed, Web of Science, and EBSCO host databases to identify articles published between 2010 and 2023 that reported incidence and mortality rates of cancer, including ADCs and NADCs among PLHIV. We compared trends and rates in PLHIV with HIV-negative adults and further assessed related risk factors. Results: A total of 1886 potentially eligible articles were screened, and of these, 36 were included in this study. More than 50% (n = 20) of these were based in high-income countries. Seventeen studies reported a higher prevalence of NADCs compared to ADCs, with twelve of these conducted in high-income countries. Conversely, eight out of twelve studies reporting a higher prevalence of ADCs versus NADCs were from low-and-middle and upper-middle-income countries. Ten studies indicated a higher incidence of ADCs (6 studies) and NADCs (4 studies) among PLHIV compared to HIV-negative individuals. In contrast, only two studies observed an increase in NADCs among the HIV-negative population. In comparing mortality, seven out of nine studies showed elevated NADC-related deaths compared to ADCs. The main risk factors identified for any cancer, NADCs, and related mortality were advancing age, and longer duration of HIV infection, while lower CD4 cell counts (<200 cells/µl), was associated with both ADC and NADC occurrences. Conclusion: Chronic HIV infection combined with advancing age in PLHIV taking antiretroviral therapy appears to have contributed to increasing cancer burden, particularly the incidence of NADCs and associated mortality. These findings stress the importance of screening for high-risk cancers among PLHIV for early detection and treatment to ensure improved outcomes.

Mastering geographically weighted regression: key considerations for building a robust model.

Geographically weighted regression (GWR) takes a prominent role in spatial regression analysis, providing a nuanced perspective on the intricate interplay of variables within geographical landscapes (Brunsdon et al., 1998). However, it is essential to have a strong rationale for employing GWR, either as an addition to, or a complementary analysis alongside, non-spatial (global) regression models (Kiani, Mamiya et al., 2023). Moreover, the proper selection of bandwidth, weighting function or kernel types, and variable choices constitute the most critical configurations in GWR analysis (Wheeler, 2021). [...].

Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study.

The incidence and mortality of hepatocellular carcinoma (HCC) in Sub-Saharan Africa is projected to increase sharply by 2040 against a backdrop of limited diagnostic and therapeutic options. Two large South African-based case control studies have developed a serum-based miRNome for Hepatitis B-associated hepatocellular carcinoma (HBV-HCC), as well as identifying their gene targets and pathways. Using a combination of RNA sequencing, differential analysis and filters including a unique molecular index count (UMI) ≥ 10 and log fold change (LFC) range > 2: <-0.5 (p < 0.05), 91 dysregulated miRNAs were characterized including 30 that were upregulated and 61 were downregulated. KEGG analysis, a literature review and other bioinformatic tools identified the targeted genes and HBV-HCC pathways of the top 10 most dysregulated miRNAs. The results, which are based on differentiating miRNA expression of cases versus controls, also develop a serum-based miRNA diagnostic panel that indicates 95.9% sensitivity, 91.0% specificity and a Youden Index of 0.869. In conclusion, the results develop a comprehensive African HBV-HCC miRNome that potentially can contribute to RNA-based diagnostic and therapeutic options.

Improved household flooring is associated with lower odds of enteric and parasitic infections in low- and middle-income countries: A systematic review and meta-analysis.

Enteric and parasitic infections such as soil-transmitted helminths cause considerable mortality and morbidity in low- and middle-income settings. Earthen household floors are common in many of these settings and could serve as a reservoir for enteric and parasitic pathogens, which can easily be transmitted to new hosts through direct or indirect contact. We conducted a systematic review and meta-analysis to establish whether and to what extent improved household floors decrease the odds of enteric and parasitic infections among occupants compared with occupants living in households with unimproved floors. Following the PRISMA guidelines, we comprehensively searched four electronic databases for studies in low- and middle-income settings measuring household flooring as an exposure and self-reported diarrhoea or any type of enteric or intestinal-parasitic infection as an outcome. Metadata from eligible studies were extracted and transposed on to a study database before being imported into the R software platform for analysis. Study quality was assessed using an adapted version of the Newcastle-Ottawa Quality Assessment Scale. In total 110 studies were eligible for inclusion in the systematic review, of which 65 were eligible for inclusion in the meta-analysis after applying study quality cut-offs. Random-effects meta-analysis suggested that households with improved floors had 0.75 times (95CI: 0.67-0.83) the odds of infection with any type of enteric or parasitic infection compared with household with unimproved floors. Improved floors gave a pooled protective OR of 0.68 (95CI: 0.58-0.8) for helminthic infections and 0.82 OR (95CI: 0.75-0.9) for bacterial or protozoan infections. Overall study quality was poor and there is an urgent need for high-quality experimental studies investigating this relationship. Nevertheless, this study indicates that household flooring may meaningfully contribute towards a substantial portion of the burden of disease for enteric and parasitic infections in low- and middle-income settings.

Using Regional Sero-Epidemiology SARS-CoV-2 Anti-S Antibodies in the Dominican Republic to Inform Targeted Public Health Response.

Incidence of COVID-19 has been associated with sociodemographic factors. We investigated variations in SARS-CoV-2 seroprevalence at sub-national levels in the Dominican Republic and assessed potential factors influencing variation in regional-level seroprevalence. Data were collected in a three-stage cross-sectional national serosurvey from June to October 2021. Seroprevalence of antibodies against the SARS-CoV-2 spike protein (anti-S) was estimated and adjusted for selection probability, age, and sex. Multilevel logistic regression was used to estimate the effect of covariates on seropositivity for anti-S and correlates of 80% protection (PT80) against symptomatic infection for the ancestral and Delta strains. A total of 6683 participants from 134 clusters in all 10 regions were enrolled. Anti-S, PT80 for the ancestral and Delta strains odds ratio varied across regions, Enriquillo presented significant higher odds for all outcomes compared with Yuma. Compared to being unvaccinated, receiving ≥2 doses of COVID-19 vaccine was associated with a significantly higher odds of anti-S positivity (OR 85.94, [10.95-674.33]) and PT80 for the ancestral (OR 4.78, [2.15-10.62]) and Delta strains (OR 3.08, [1.57-9.65]) nationally and also for each region. Our results can help inform regional-level public health response, such as strategies to increase vaccination coverage in areas with low population immunity against currently circulating strains.

The uncertain role of substandard and falsified medicines in the emergence and spread of antimicrobial resistance.

Approximately 10% of antimicrobials used by humans in low- and middle-income countries are estimated to be substandard or falsified. In addition to their negative impact on morbidity and mortality, they may also be important drivers of antimicrobial resistance. Despite such concerns, our understanding of this relationship remains rudimentary. Substandard and falsified medicines have the potential to either increase or decrease levels of resistance, and here we discuss a range of mechanisms that could drive these changes. Understanding these effects and their relative importance will require an improved understanding of how different drug exposures affect the emergence and spread of resistance and of how the percentage of active pharmaceutical ingredients in substandard and falsified medicines is temporally and spatially distributed.

Stakeholder's perspectives on acceptable interventions for promoting hypertension medication adherence in Namibia: nominal group technique.

OBJECTIVE: To determine the most acceptable hypertension intervention package to promote hypertension adherence based on stakeholders' perspectives. DESIGN: We employed the nominal group technique method and purposively sampled and invited key stakeholders offering hypertension services and patients with hypertension. Phase 1 was focused on determining barriers to hypertension adherence, phase 2 on enablers and phase 3 on the strategies. We employed the ranking method based on a maximum of 60 scores to establish consensus regarding hypertension adherence barriers, enablers and proposed strategies. SETTING AND PARTICIPANTS: 12 key stakeholders were identified and invited to participate in the workshop in Khomas region. Key stakeholders included subject matter experts in non-communicable diseases, family medicine and representatives of our target population (hypertensive patients). RESULTS: The stakeholders reported 14 factors as barriers and enablers to hypertension adherence. The most important barriers were: lack of knowledge on hypertension (57 scores), unavailability of drugs (55 scores) and lack of social support (49 scores). Patient education emerged as the most important enabler (57 scores), availability of drugs emerged second (53 scores) and third having a support system (47 scores). Strategies were 17 and ranked as follows: continuous patient education as the most desirable (54 scores) strategy to help promote hypertension adherence, followed by developing a national dashboard to primarily monitor stock (52 scores) and community support groups for peer counselling (49 scores). CONCLUSIONS: Multifaceted educational intervention package targeting patient and healthcare system factors may be considered in implementing Namibia's most acceptable hypertension package. These findings will offer an opportunity to promote adherence to hypertension therapy and reduce cardiovascular outcomes. We recommend a follow-up study to evaluate the proposed adherence package's feasibility.

Spatial variations in STIs among women enrolled in HIV prevention clinical trials in Durban, KwaZulu-Natal, South Africa.

South Africa is faced with a high HIV and STI prevalence and incidence, respectively, with pockets of high burden areas driving these diseases. Localised monitoring of the HIV epidemic and STI endemic would enable more effective targeted prevention strategies. We assessed spatial variations in curable STI incidence among a cohort of women enrolled in HIV prevention clinical trials between 2002 and 2012. STI incidence rates from 7557 South African women enrolled in five HIV prevention trials were geo-mapped using participant household GPS coordinates. Age and period standardised incidence rates were calculated for 43 recruitment areas and Bayesian conditional autoregressive areal spatial regression (CAR) was used to identify significant patterns and spatial patterns of STI infections in recruitment communities. Overall age and period standardised STI incidence rate were estimated as 15 per 100 PY and ranged from 6 to 24 per 100 PY. We identified five significant STI high risk areas with higher-than-expected incidence of STIs located centrally (three-locations) and southern neighbouring areas of Durban (two-locations). Younger age (<25), not married/cohabitating, parity <3 and poor education were all significant correlates of high STI communities. Findings demonstrate sustained STI incidence rates across the greater Durban area. The role of STI incidence in HIV acquisition in high HIV endemic areas need to be revisited as current highly effective PrEP interventions do not protect from STI acquisition. In these settings there is an urgent need for integrative HIV and STI prevention and treatment services.

Pre- and post-intervention survey on lung cancer awareness among adults in selected communities in KwaZulu-Natal, South Africa: A quasi-experimental study.

Background: Lung cancer remains the number one cause of cancer mortality estimated at 1.8 million deaths. There are limited studies in resource poor countries regarding knowledge, attitudes and practices towards lung cancer. Objective: This study aimed to assess the effects of a lung cancer awareness intervention in selected communities in KwaZulu- Natal, South Africa. Materials and Methods: A quasi-experimental study design was conducted in the selected communities in KwaZulu-Natal. A community intervention was administered in the communities after a baseline survey. The intervention effects were assessed a month after implementation. Results: There were statistical differences in the mean age (p<0.001) and proportion of males and females (p<0.001) at baseline and post-intervention. There were no differences in terms of smoking status (p=0.958), however, there was a reduction in the number of cigarettes smoked per day (p<0.001) and the number of packs smoked per week (p=0.026). The mean knowledge score increased from 41.8% (95% CI 35.7 - 47.9) at baseline to 59.9 (95% CI 53.8 - 66.0) post-intervention (p<0.001). The proportion of participants who were aware that lung cancer can be detected early increased from 46.5% (95% CI 39.1 - 53.9) at baseline to 81.1% (95% CI 71.7 - 87.9) post-intervention (p<0.001). The intervention had a statistically significant effect (aOR 4.370, 95% CI 1.477-12.928) on the level of lung cancer knowledge in the selected communities (p<0.001). Conclusions: Interventions increasing the recognition of signs and symptoms, focusing on the importance of early detection and health seeking behaviour (including screening), smoking cessation, and addressing the perceived health system barriers are required.

Drug-resistant bacterial infections: We need urgent action and investment that focus on the weakest link.

Despite high mortality and morbidity, drug-resistant bacterial infections remain the forgotten pandemic. We argue for strengthening of diagnostics, WASH (water, sanitation, and hygiene) and infection prevention and control to reduce drug-resistant infections, as an integral part of sustainable high-quality health services, particularly in low- and middle-income countries.

Prevalence and distribution pattern of malaria and soil-transmitted helminth co-endemicity in sub-Saharan Africa, 2000-2018: A geospatial analysis.

BACKGROUND: Limited understanding exists about the interactions between malaria and soil-transmitted helminths (STH), their potential geographical overlap and the factors driving it. This study characterised the geographical and co-clustered distribution patterns of malaria and STH infections among vulnerable populations in sub-Saharan Africa (SSA). METHODOLOGY/PRINCIPAL FINDINGS: We obtained continuous estimates of malaria prevalence from the Malaria Atlas Project (MAP) and STH prevalence surveys from the WHO-driven Expanded Special Project for the Elimination of NTDs (ESPEN) from Jan 1, 2000, to Dec 31, 2018. Although, MAP provides datasets on the estimated prevalence of Plasmodium falciparum at 5km x 5km fine-scale resolution, we calculated the population-weighted prevalence of malaria for each implementation unit to ensure that both malaria and STH datasets were on the same spatial resolution. We incorporated survey data from 5,935 implementation units for STH prevalence and conducted the prevalence point estimates before and after 2003. We used the bivariate local indicator of spatial association (LISA analysis) to explore potential co-clustering of both diseases at the implementation unit levels among children aged 2-10 years for P. falciparum and 5-14 years for STH, living in SSA. Our analysis shows that prior to 2003, a greater number of SSA countries had a high prevalence of co-endemicity with P.falciparium and any STH species than during the period from 2003-2018. Similar prevalence and distribution patterns were observed for the co-endemicity involving P.falciparum-hookworm, P.falciparum-Ascaris lumbricoides and P.falciparum-Trichuris trichiura, before and after 2003. We also observed spatial variations in the estimates of the prevalence of P. falciparum-STH co-endemicity and identified hotspots across many countries in SSA with inter-and intra-country variations. High P. falciparum and high hookworm co-endemicity was more prevalent in West and Central Africa, whereas high P. falciparum with high A. lumbricoides and high P. falciparum with high T. trichiura co-endemicity were more predominant in Central Africa, compared to other sub-regions in SSA. CONCLUSIONS/SIGNIFICANCE: Wide spatial heterogeneity exists in the prevalence of malaria and STH co-endemicity within the regions and within countries in SSA. The geographical overlap and spatial co-existence of malaria and STH could be exploited to achieve effective control and elimination agendas through the integration of the vertical control programmes designed for malaria and STH into a more comprehensive and sustainable community-based paradigm.

Can a conditional financial incentive (CFI) reduce socio-demographic inequalities in home-based HIV testing uptake? A secondary analysis of the HITS clinical trial intervention in rural South Africa.

In sub-Saharan Africa, home-based HIV testing interventions are designed to reach sub-populations with low access to HIV testing such as men, younger or less educated people. Combining these interventions with conditional financial incentives (CFI) has been shown to be effective to increase testing uptake. CFI are effective for one-off health behaviour change but whether they operate differentially on different socio-demographic groups is less clear. Using data from the HITS trial in South Africa, we investigated whether a CFI was able to reduce existing home-based HIV testing uptake inequalities observed by socio-demographic groups. Residents aged ≥15 years in the study area were assigned to an intervention arm (16 clusters) or a control arm (29 clusters). In the intervention arm, individuals received a food voucher (∼3.5 US dollars) if they accepted to take a home-based HIV test. Testing uptake differences were considered for socio-demographic (sex, age, education, employment status, marital status, household asset index) and geographical (urban/rural living area, distance from clinic) characteristics. Among the 37,028 residents, 24,793 (9290 men, 15,503 women) were included in the analysis. CFI increased significantly testing uptake among men (39.2% vs 25.2%, p < 0.001) and women (45.9% vs 32.0%, p < 0.001) with similar absolute increase between men and women. Uptake was higher amongst the youngest or least educated individuals, and amongst single (vs in union) or unemployed men. Absolute uptake increase was also significantly higher amongst these groups resulting in increasing socio-demographic differentials for home-based HIV testing uptake. However, because these groups are known to have less access to other public HIV testing services, CFI could reduce inequalities for HIV testing access in our specific context. Although CFI significantly increased home-based HIV testing uptake, it did not do so differentially by socio-demographic group. Future interventions using CFI should make sure that the intervention alone does not increase existing health inequities.

Excess Mortality Attributable to Hospital-Acquired Antimicrobial-Resistant Infections: A 2-Year Prospective Surveillance Study in Northeast Thailand.

Background: Quantifying the excess mortality attributable to antimicrobial-resistant (AMR) bacterial infections is important for assessing the potential benefit of preventive interventions and for prioritization of resources. However, there are few data from low- and middle-income countries. Methods: We conducted a 2-year prospective surveillance study to estimate the excess mortality attributable to AMR infections for all types of hospital-acquired infection (HAI), and included bacterial species that were both locally relevant and included in the World Health Organization priority list. Twenty-eight-day mortality was measured. Excess mortality and population attributable fraction (PAF) of mortality caused by AMR infections compared to antimicrobial-susceptible (AMS) infections, adjusted for predefined confounders, were calculated. Results: We enrolled 2043 patients with HAIs. The crude 28-day mortality of patients with AMR and AMS infections was 35.5% (491/1385) and 23.1% (152/658), respectively. After adjusting for prespecified confounders, the estimated excess mortality attributable to AMR infections was 7.7 (95% confidence interval [CI], 2.2-13.2) percentage points. This suggests that 106 (95% CI, 30-182) deaths among 1385 patients with AMR infections might have been prevented if all of the AMR infections in this study were AMS infections. The overall PAF was 16.3% (95% CI, 1.2%-29.1%). Among the bacteria under evaluation, carbapenem-resistant Acinetobacter baumannii was responsible for the largest number of excess deaths. Among all types of infection, urinary tract infections were associated with the highest number of excess deaths, followed by lower respiratory tract infections and bloodstream infections. Conclusions: Estimating and monitoring excess mortality attributable to AMR infections should be included in national action plans to prioritize targets of preventive interventions. Clinical Trials Registration: NCT03411538.

Mapping local variation in household overcrowding across Africa from 2000 to 2018: a modelling study.

BACKGROUND: Household overcrowding is a serious public health threat associated with high morbidity and mortality. Rapid population growth and urbanisation contribute to overcrowding and poor sanitation in low-income and middle- income countries, and are risk factors for the spread of infectious diseases, including COVID-19, and antimicrobial resistance. Many countries do not have adequate surveillance capacity to monitor household overcrowding. Geostatistical models are therefore useful tools for estimating household overcrowding. In this study, we aimed to estimate household overcrowding in Africa between 2000 and 2018 by combining available household survey data, population censuses, and other country-specific household surveys within a geostatistical framework. METHODS: We used data from household surveys and population censuses to generate a Bayesian geostatistical model of household overcrowding in Africa for the 19-year period between 2000 and 2018. Additional sociodemographic and health-related covariates informed the model, which covered 54 African countries. FINDINGS: We analysed 287 surveys and population censuses, covering 78 695 991 households. Spatial and temporal variability arose in household overcrowding estimates over time. In 2018, the highest overcrowding estimates were observed in the Horn of Africa region (median proportion 62% [IQR 57-63]); the lowest regional median proportion was estimated for the north of Africa region (16% [14-19]). Overall, 474·4 million (95% uncertainty interval [UI] 250·1 million-740·7 million) people were estimated to be living in overcrowded conditions in Africa in 2018, a 62·7% increase from the estimated 291·5 million (180·8 million-417·3 million) people who lived in overcrowded conditions in the year 2000. 48·5% (229·9 million) of people living in overcrowded conditions came from six African countries (Nigeria, Ethiopia, Democratic Republic of the Congo, Sudan, Uganda, and Kenya), with a combined population of 538·3 million people. INTERPRETATION: This study incorporated survey and population censuses data and used geostatistical modelling to estimate continent-wide overcrowding over a 19-year period. Our analysis identified countries and areas with high numbers of people living in overcrowded conditions, thereby providing a benchmark for policy planning and the implementation of interventions such as in infectious disease control. FUNDING: UK Department of Health and Social Care, Wellcome Trust, Bill & Melinda Gates Foundation.

Factors influencing poor medication adherence amongst patients with chronic disease in low-and-middle-income countries: A systematic scoping review.

Background: Poor medication adherence among patients with Chronic Diseases is one of the significant health problems globally. Despite this, evidence on chronic medication adherence in low and middle-income countries is unclear. Objective: This scoping review aimed to identify factors influencing poor medication adherence amongst patients with chronic diseases in low and middle-income countries. Methods: We searched studies exploring factors influencing poor medication adherence amongst patients in low and middle-income countries across the following databases published between 2008 to 2018: Public or publisher Medline, Google scholar, Cumulated Index to Nursing and Allied Health Literature, Health Source, and Medline with full text via Elton B. Stephen's Company host. Methodological quality assessment of the primary studies was done as recommended by Levac, Colquhoun, and O'Brien (2010) review using a Mixed-Method Appraisal Tool 2018. We reported the results following the Preferred Reporting Item for Systematic reviews and Meta-Analyses extension for Scoping Review guidelines. Results: From the initial 154 records screened, we identified six (6) eligible studies that presented evidence on factors influencing poor medication adherence amongst patients in low and middle-income countries. Studies included were from the following countries: Jordan, South Africa, Guatemala, Ethiopia, Indonesia, India, and Palestine. Kappa agreement of the full article screening shows that there was 76.92% agreement versus 58.12% expected by chance which constitutes a considerably good agreement between screeners (Kappa statistic = 0.45 and p-value <0.05). Of the six included studies that underwent methodological quality, five scored 100%, which is regarded as the highest score the remaining one scored between 50-75%, indicating a moderate to low risk bias overall. All included studies presented evidence on medication adherence as being in either knowledge of the diseases, attitudes towards medication taking, beliefs that a patient holds about the treatment or disease, and quality control amongst chronic diseases patients. Conclusions: Our scoping review provides evidence that poor medication adherence in LMICs is influenced by a lack of knowledge, negative attitudes, and negative beliefs, leading to poor quality of life. There is limited research evidence on the effect of patients' beliefs and perceptions on medication adherence in low and middle-income countries. We call upon further research on beliefs, perceptions, and effectiveness of interventions towards chronic medication adherence in low and middle-income countries.

A Cross-Sectional Study on Hypertension Medication Adherence in a High-Burden Region in Namibia: Exploring Hypertension Interventions and Validation of the Namibia Hill-Bone Compliance Scale.

In Namibia, the prevalence of hypertension among women and men aged 35−64 years is high, ranging from 44% to 57%. In this study, we aimed to determine adherence and predictors to antihypertensive therapy in Khomas region, Namibia. A cross-sectional study was performed to consecutively sample 400 patients from urban and peri-urban settings in Namibia. Results were validated using the Hill-Bone Compliance to High Blood Pressure Therapy Scale. Crude associations between predictors of adherence and compliance were tested using the Pearson chi-square test. A multivariable logistic regression analysis was then performed on adherence variables found to be significant to adjust for confounders, and the results are presented as adjusted odds ratios (aOR) with 95% confidence intervals. A total of 400 patients participated in this study. The participants' mean age and standard deviation were Mean ± SD = 48.9 ± 12.5. In this study, 351 (87.7%) patients were estimated to have good adherence. Education, employment, and the presence of other chronic diseases were associated with adherence. Following multivariate adjustment, the following factors were significantly associated and are therefore predictors of adherence (95%CI, p < 0.005): receiving enough medication at last check-up until next one (OR = 5.44, CI 1.76−16.85), lack of encouragement from family and friends (OR = 0.11 (0.03−0.42)), and attendance of follow-ups on schedule (OR = 8.49, CI = 3.82−18.85). The success of hypertension therapy is dependent on the healthcare systems and healthcare professionals in supplying enough medication, support of friends/family, and maintaining scheduled follow-ups. A combination of interventions using low-cost mobile technology led by healthcare professionals could be endorsed. To fully practice universal access to medication, public and private hospitals in Namibia should collaborate.

Health trends, inequalities and opportunities in South Africa's provinces, 1990-2019: findings from the Global Burden of Disease 2019 Study.

BACKGROUND: Over the last 30 years, South Africa has experienced four 'colliding epidemics' of HIV and tuberculosis, chronic illness and mental health, injury and violence, and maternal, neonatal, and child mortality, which have had substantial effects on health and well-being. Using data from the 2019 Global Burden of Diseases, Injuries and Risk Factors Study (GBD 2019), we evaluated national and provincial health trends and progress towards important Sustainable Development Goal targets from 1990 to 2019. METHODS: We analysed GBD 2019 estimates of mortality, non-fatal health loss, summary health measures and risk factor burden, comparing trends over 1990-2007 and 2007-2019. Additionally, we decomposed changes in life expectancy by cause of death and assessed healthcare system performance. RESULTS: Across the nine provinces, inequalities in mortality and life expectancy increased over 1990-2007, largely due to differences in HIV/AIDS, then decreased over 2007-2019. Demographic change and increases in non-communicable diseases nearly doubled the number of years lived with disability between 1990 and 2019. From 1990 to 2019, risk factor burdens generally shifted from communicable and nutritional disease risks to non-communicable disease and injury risks; unsafe sex remained the top risk factor. Despite widespread improvements in healthcare system performance, the greatest gains were generally in economically advantaged provinces. CONCLUSIONS: Reductions in HIV/AIDS and related conditions have led to improved health since 2007, though most provinces still lag in key areas. To achieve health targets, provincial governments should enhance health investments and exchange of knowledge, resources and best practices alongside populations that have been left behind, especially following the COVID-19 pandemic.

HIV-1 drug resistance in adults and adolescents on protease inhibitor-based antiretroviral therapy in KwaZulu-Natal Province, South Africa.

OBJECTIVES: In low-middle-income countries, increasing levels of HIV drug resistance (HIVDR) on second-line protease inhibitor (PI)-based regimens are a cause for concern given the limited drug options for third-line antiretroviral therapy (ART). We conducted a retrospective analysis of routine HIV-1 genotyping laboratory data from KwaZulu-Natal, South Africa, to describe the frequency and patterns of HIVDR mutations and their consequent impact on standardised third-line regimens. METHODS: This was a cross-sectional analysis of all HIV-1 genotypic resistance tests conducted by the National Health Laboratory Service in KwaZulu-Natal (January 2015 to December 2016) for adults and adolescents (age ≥10 years) on second-line PI-based ART with virological failure. We assigned a third-line regimen to each record based on a national treatment algorithm and calculated the genotypic susceptibility score (GSS) for that regimen. RESULTS: Of 348 samples analysed, 287 (82.5%) had at least one drug resistance mutation (DRM) and 114 (32.8%) had at least one major PI DRM. Major PI resistance was associated with longer duration on second-line ART (aOR per 6-months = 1.11, 95% CI 1.04-1.19) and older age (aOR = 1.03, 95% CI 1.01-1.05). Of 112 patients requiring third-line ART, 12 (10.7%) had a GSS of <2 for the algorithm-assigned third-line regimen. CONCLUSION: One-third of people failing second-line ART had significant PI DRMs. A subgroup of these individuals had extensive HIVDR, where the predicted activity of third-line ART was suboptimal, highlighting the need for continuous evaluation of outcomes on third-line regimens and close monitoring for emergent HIV-1 integrase inhibitor resistance.