HIV drug resistance (HIVDR) surveillance is an important tool to monitor threats to progress towards epidemic control. The characterization of HIVDR in Nigeria at the national level is needed to ...inform both clinical decisions and population-level HIV policy strategies. This study uses data obtained from the Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS) to describe the prevalence and distribution of HIVDR in Nigeria.
NAIIS was a cross-sectional, population-based survey of households throughout Nigeria in 2018. NAIIS was designed to provide estimates of HIV prevalence and related health indicators from a nationally representative sample. The study population included participants aged 15-64 years who tested positive for HIV, had a viral load at least 1000 copies/ml, and had available HIV drug resistance genotypes. HIV isolates were genotyped to detect drug resistance mutations. Individual characteristics of study participants associated with HIVDR were identified using a weighted multivariable logistic regression model.
Of 1355 respondents with available HIV genotypes, 293 (19%) had evidence of drug-resistant mutations (DRMs) that conferred resistance to at least one antiretroviral drug. The majority of DRMs observed conferred resistance to NNRTIs (17.6%) and NRTIs (11.2%). HIVDR was associated with being ART-experienced, longer duration on ART, and lower CD4+ count but not sociodemographic characteristics.
The population level DRM prevalence in Nigeria was consistent with what would be expected in a mature HIV treatment landscape. The continued roll out of dolutegravir-anchored regimens should mitigate the impact of NNRTI resistance on population viral load suppression and progress towards epidemic control.
The Zambian government has implemented a public health response to control the HIV epidemic in the country. Zambia conducted a population-based HIV impact assessment (ZAMPHIA) survey in 2021 to ...assess the status of the HIV epidemic to guide its public health programs.
ZAMPHIA 2021 was a cross-sectional two-stage cluster sample household survey among persons aged ≥15 years conducted in Zambia across all 10 provinces. Consenting participants were administered a standardized questionnaire and whole blood was tested for HIV according to national guidelines. HIV-1 viral load (VL), recent HIV infection, and antiretroviral medications were tested for in HIV-seropositive samples. Viral load suppression (VLS) was defined as <1000 copies/ml. ZAMPHIA 2021 results were compared to ZAMPHIA 2016 for persons aged 15-59 years (i.e., the overlapping age ranges). All estimates were weighted to account for nonresponse and survey design.
During ZAMPHIA 2021, of 25 483 eligible persons aged ≥15 years, 18 804 (73.8%) were interviewed and tested for HIV. HIV prevalence was 11.0% and VLS prevalence was 86.2% overall, but was <80% among people living with HIV aged 15-24 years and in certain provinces. Among persons aged 15-59 years, from 2016 to 2021, HIV incidence declined from 0.6% to 0.3% ( P -value: 0.07) and VLS prevalence increased from 59.2% to 85.7% ( P -value: <0.01).
Zambia has made substantial progress toward controlling the HIV epidemic from 2016 to 2021. Continued implementation of a test-and-treat strategy, with attention to groups with lower VLS in the ZAMPHIA 2021, could support reductions in HIV incidence and improve overall VLS in Zambia.
Major depression is the most common neuropsychiatric disorder among people living with HIV (PLWH) and is predictive of high morbidity and mortality among them. This study estimated the prevalence and ...explored factors associated with depression among PLWH in two rural secondary health facilities providing anti-retroviral therapy (ART) services in Southwestern Nigeria between September and December 2020. The Patient Health Questionnaire-9 (PHQ-9) was used to screen and identify PLWH aged 18 years or older with depression. Descriptive statistics, bivariate and multivariate analyses were performed with SPSS version 23. A total of 172 respondents were screened. The prevalence of depression was 16.3% (95% CI 11.1%, 22.7%). Mild, moderate, and moderately severe depression was identified in 17 (9.9%), 8(4.7%) and 3(1.7%) of the participants, respectively. One (0.6%) respondent had suicidal ideation. Of PLWH with any depression, 20/28(71.4%) were within the 40-59 years of age range. None of the participants was on antidepressants. The factor most associated with depression was hypertension, with adjusted odd ratios of 9.8(95% CI 3.5-27.3, p < 0.0001). The study highlights the importance of screening for the severity of depression among PLWH in rural hospitals providing ART services in Africa. PLWH with comorbid hypertension were more likely to suffer from some form of depression.
Our objective was to assess factors associated with health-related quality of life (HRQoL) among men who have sex with men (MSM) living with or those not living with HIV in Nigeria. A cross-sectional ...subset of adult MSM in the ongoing TRUST/RV368 HIV prevention and treatment study were recruited and completed the World Health Organization quality of life in HIV infection (WHOQOL-BREF) questionnaire. The tool comprises physical health, psychological health, social relationships and environmental health domains from which scores were extracted. T-tests were used to compare mean HRQoL scores between participants living with or those not living with HIV and among persons living with HIV who had been on antiretroviral therapy for ≥1 year or <1 year. Of 322 study participants, 186 (57.8%) were living with HIV. The mean scores were significantly lower for participants living with HIV as compared to those not living with HIV in physical health, psychological health and social relationship domains. Among persons living with HIV and taking ART, scores were significantly lower for those whose duration was <1 year as compared to ≥1 year regarding physical health and psychological health. Strategies to improve HIV prevention and early detection and linkage to HIV care may improve HRQoL.
People living with HIV are vulnerable to cardiometabolic diseases. We assessed the prevalence of cardiometabolic risk factors (CMRF) and associations with sexual stigma and depression among sexual ...and gender minorities (SGM) in Abuja and Lagos, Nigeria.
The TRUST/RV368 study enrolled SGM between March 2013 and February 2020. Participants were assessed for depression, sexual stigma, and CMRF. Robust multinomial logistic regression was used to estimate adjusted odds ratio (aORs) and 95% confidence intervals (CIs) for associations of depression, sexual stigma, and other factors with increasing numbers of CMRF.
Among 761 SGM, the mean age was 25.0 ± 6.0 years; 580 (76%) identified as cisgender men, 641 (84%) had ≥1 CMRF, 355 (47%) had mild-severe depression, and 405 (53%) reported moderate-high sexual stigma. Compared with individuals without depression, those with mild (aOR 8.28; 95% CI: 4.18 to 16.40) or moderate-severe depression (aOR 41.69; 95% CI: 9.60 to 181.04) were more likely to have 3-5 CMRF. Individuals with medium (aOR 3.17; 95% CI: 1.79 to 5.61) and high sexual stigma (aOR 14.42; 95% CI: 2.88 to 72.29) compared with those with low sexual stigma were more likely to have 3-5 CMRF. Participants age 25-34 years were less likely to have 3-5 CMRF (aOR 0.41; 95% CI: 0.23 to 0.73) compared with participants age younger than 25 years.
CMRF increased with severity of depression and sexual stigma, potentially predisposing SGM living with HIV to cardiometabolic diseases. Integrating interventions that address depression and sexual stigma in HIV care programs for SGM may improve cardiometabolic outcomes.
Understanding the correlates of disengagement from HIV care and treatment failure during second-line antiretroviral therapy (ART) could inform interventions to improve clinical outcomes among people ...living with HIV (PLHIV).
We conducted a retrospective cohort study of PLHIV aged >15 years who started second-line ART at a tertiary center in Nigeria between 2005 and 2017. Participants were considered to have disengaged from care if they had not returned within a year after each clinic visit. Cox proportional hazard models were used to investigate factors associated with: (1) viral failure (HIV-1 RNA >1000 copies/mL), (2) immunologic failure (CD4 count decrease or <100 cells/mm3), and (3) severe weight loss (>10% of bodyweight), after >6 months of second-line ART.
Among 1031 participants, 33% (341) disengaged from care during a median follow-up of 6.9 years (interquartile range 3.7-8.5). Of these, 26% (89/341) subsequently reentered care. Disengagement was associated with male gender, age <30 years, lower education level, and low CD4 count at second-line ART initiation. Among participants with endpoint assessments available, 20% (112/565) experienced viral failure, 32% (257/809) experienced immunologic failure, and 23% (190/831) experienced weight loss. A lower risk of viral failure was associated with professional occupations compared with elementary: adjusted hazard ratio 0.17 (95% confidence interval 0.04 to 0.70).
Adverse outcomes were common during second-line ART. However, reengagement is possible and resources should be allocated to focus on retaining PLHIV in care and providing services to trace and reengage those who have disengaged from care.
Nigeria has the highest number of AIDS-related deaths in the world. In this study, we characterised the HIV-1 molecular epidemiology by analysing 1442 HIV-1 pol sequences collected 1999-2014 from ...four geopolitical zones in Nigeria using state-of-the-art maximum-likelihood and Bayesian phylogenetic analyses. The main circulating forms were the circulating recombinant form (CRF) 02_AG (44% of the analysed sequences), CRF43_02G (16%), and subtype G (8%). Twenty-three percent of the sequences represented unique recombinant forms (URFs), whereof 37 (11%) could be grouped into seven potentially novel CRFs. Bayesian phylodynamic analysis suggested that five major Nigerian HIV-1 sub-epidemics were introduced in the 1960s and 1970s, close to the Nigerian Civil War. The analysis also indicated that the number of effective infections decreased in Nigeria after the introduction of free antiretroviral treatment in 2006. Finally, Bayesian phylogeographic analysis suggested gravity-like dynamics in which virus lineages first emerge and expand within large urban centers such as Abuja and Lagos, before migrating towards smaller rural areas. This study provides novel insight into the Nigerian HIV-1 epidemic and may have implications for future HIV-1 prevention strategies in Nigeria and other severely affected countries.
We isolated a strain of human mycoplasma that promotes lymphomagenesis in SCID mice, pointing to a p53-dependent mechanism similar to lymphomagenesis in uninfected p53−/− SCID mice. Additionally, ...mycoplasma infection in vitro reduces p53 activity. Immunoprecipitation of p53 in mycoplasma-infected cells identified several mycoplasma proteins, including DnaK, a member of the Hsp70 chaperon family. We focused on DnaK because of its ability to interact with proteins. We demonstrate that mycoplasma DnaK interacts with and reduces the activities of human proteins involved in critical cellular pathways, including DNA-PK and PARP1, which are required for efficient DNA repair, and binds to USP10 (a key p53 regulator), impairing p53-dependent anticancer functions. This also reduced the efficacy of anticancer drugs that depend on p53 to exert their effect. mycoplasma was detected early in the infected mice, but only low copy numbers of mycoplasma DnaK DNA sequences were found in some primary and secondary tumors, pointing toward a hit-and-run/hide mechanism of transformation. Uninfected bystander cells took up exogenous DnaK, suggesting a possible paracrine function in promoting malignant transformation, over and above cells infected with the mycoplasma. Phylogenetic amino acid analysis shows that other bacteria associated with human cancers have similar DnaKs, consistent with a common mechanism of cellular transformation mediated through disruption of DNA-repair mechanisms, as well as p53 dysregulation, that also results in cancer-drug resistance. This suggests that the oncogenic properties of certain bacteria are DnaK-mediated.
Abstract
Background
Clearance of hepatitis C virus (HCV) results in rapid changes in metabolic parameters early in direct-acting antiviral (DAA) therapy. Long-term changes after sustained virologic ...response (SVR) remain unknown.
Methods
We investigated longitudinal changes in metabolic and inflammatory outcomes in chronic hepatitis C (CHC) patients: low-density lipoprotein (LDL), high-density lipoprotein, triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) using a general linear model for repeated measurements at 5 clinical time points and by human immunodeficiency virus (HIV) coinfection and IFNL4 genotype.
Results
The mean LDL increased markedly during DAA therapy (pre-DAA, 86.6 to DAA, 107.4 mg/dL; P < .0001), but then it decreased to 97.7 mg/dL by post-SVR year 1 (P < .001 compared with DAA; P = .0013 compared with SVR). In patients who carry the IFNL4-ΔG allele, mean LDL increased during treatment, then decreased at post-SVR year 1; however, in patients with TT/TT, genotype did not change during and after DAA treatment. The mean ALT and AST normalized rapidly between pre-DAA and DAA, whereas only mean ALT continued to decrease until post-SVR. Metabolic and inflammatory outcomes were similar by HIV-coinfection status.
Conclusions
Changes in LDL among CHC patients who achieved SVR differed by IFNL4 genotype, which implicates the interferon-λ4 protein in metabolic changes observed in HCV-infected patients.
Because data on the determinants of the HIV care continuum from key populations such as men who have sex with men (MSM) in resource-limited settings are limited, the study aimed to characterize HIV ...care continuum outcomes and assess individual and network barriers to progression through the HIV care continuum among MSM in Abuja and Lagos, Nigeria.
TRUST/RV368 study used respondent-driven sampling to accrue MSM into community-based clinics in Nigeria. Participants received HIV testing at enrollment. HIV-infected participants were offered antiretroviral therapy (ART) with HIV RNA testing every 3 months (Abuja) or 6 months (Lagos). Multiple logistic regression models were used to calculate adjusted odds ratios for factors associated with each point in the HIV care continuum, including HIV testing, ART initiation, and 6-month viral suppression.
A total of 1506 MSM were recruited, 1178 (78.2%) tested for HIV and 369 (31.3%) were HIV positive newly diagnosed. Of these, 188 (50.1%) initiated ART, 136 (72.3%) completed 6 months, and 96 (70.6%) were virally suppressed. Larger network size and stronger social network support were each positively associated with HIV testing uptake. Factors associated with ART initiation were higher education and stronger social network support. Having stronger social network support was associated with increased odds of viral suppression at 6 months.
Social determinants of health potentiated increased HIV care continuum outcomes. Integration of HIV prevention, HIV counseling and testing services, and universal coverage of ART into a community-based clinic is critical in achieving better HIV care continuum outcomes.
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