Differences in neutralizing antibody sensitivities and envelope characteristics indicate distinct antigenic properties of Nigerian HIV-1 subtype G and CRF02_AG.

The magnitude of the HIV-1 epidemic in Nigeria is second only to the subtype C epidemic in South Africa, yet the subtypes prevalent in Nigeria require further characterization. A panel of 50 subtype G and 18 CRF02_AG Nigerian HIV-1 pseudoviruses (PSV) was developed and envelope coreceptor usage, neutralization sensitivity and cross-clade reactivity were characterized. These PSV were neutralized by some antibodies targeting major neutralizing determinants, but potentially important differences were observed in specific sensitivities (eg. to sCD4, MPER and V2/V3 monoclonal antibodies), as well as in properties such as variable loop lengths, number of potential N-linked glycans and charge, demonstrating distinct antigenic characteristics of CRF02_AG and subtype G. There was preferential neutralization of the matched CRF/subtype when PSV from subtype G or CRF02_AG were tested using pooled plasma. These novel Nigerian PSV will be useful to study HIV-1 CRF- or subtype-specific humoral immune responses for subtype G and CRF02_AG.

HIV risk behaviour, viraemia, and transmission across HIV cascade stages including low-level viremia: Analysis of 14 cross-sectional population-based HIV Impact Assessment surveys in sub-Saharan Africa.

As antiretroviral treatment (ART) coverage for people living with HIV (PLHIV) increases, HIV programmes require up-to-date information about evolving HIV risk behaviour and transmission risk, including those with low-level viremia (LLV; >50 to ≤1000 copies/mL), to guide prevention priorities. We aimed to assess differences in sexual risk behaviours, distribution of viral load (VL) and proportion of transmission across PLHIV subgroups. We analysed data from Population-based HIV Impact Assessment surveys in 14 sub-Saharan African countries during 2015-2019. We estimated adjusted prevalence ratios (aPR) of self-reported HIV high-risk behaviour (multiple partners and condomless sex) across cascade stages via generalised estimation equations. We modelled the proportions of transmission from each subgroup using relative self-reported sexual risk, a Hill function for transmission rate by VL, and proportions within cascade stages from surveys and UNAIDS country estimates for 2010-2020. Compared to PLHIV with undetectable VL (≤50 copies/mL), undiagnosed PLHIV (aPR women: 1.28 [95% CI: 1.08-1.52]; men: 1.61 [1.33-1.95]) and men diagnosed but untreated (2.06 [1.52-2.78]) were more likely to self-report high-risk sex. High-risk behaviour was not significantly associated with LLV. Mean VL was similar among undiagnosed, diagnosed but untreated, and on ART but non-suppressed sub-groups. Across surveys, undiagnosed and diagnosed but untreated contributed most to transmission (40-91% and 1-41%, respectively), with less than 1% from those with LLV. Between 2010 and 2020, the proportion of transmission from individuals on ART but non-suppressed increased. In settings with high ART coverage, effective HIV testing, ART linkage, and retention remain priorities to reduce HIV transmission. Persons with LLV are an increasing share of PLHIV but their contribution to HIV transmission was small. Improving suppression among PLHIV on ART with VL ≥1000 copies/mL will become increasingly important.

Comparison of HIV prevalence, incidence, and viral load suppression in Zambia population-based HIV impact assessments from 2016 and 2021.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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.

Prevalence of depression among people living with HIV in rural hospitals in South-Western Nigeria-Association with clinico-demographic factors.

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.

Determinants of Preexposure Prophylaxis Cascade Among Sexual and Gender Minorities in Nigeria.

BACKGROUND: Preexposure prophylaxis (PrEP) is effective in preventing human immunodeficiency virus (HIV) infection among sexual and gender minorities (SGMs). We evaluated the characteristics associated with engagement in 7 steps of the PrEP cascade among SGMs in Nigeria. METHODS: Sexual and gender minorities without HIV from the Abuja site of TRUST/RV368 cohort who were surveyed on awareness of and willingness to use PrEP were approached for PrEP initiation upon availability of oral daily PrEP. To understand gaps in the uptake of oral daily PrEP, we categorized the HIV PrEP cascade as (i) education about PrEP, (ii) interest in PrEP, (iii) successful contact, (iv) appointment scheduled, (v) appointment attendance, (vi) PrEP initiation, and (vii) plasma protective levels of tenofovir disoproxil fumarate. Multivariable logistic regression models were used to determine factors associated with each of the 7 steps in the HIV PrEP cascade. RESULTS: Of 788 participants, 718 (91.1%) showed interest in taking oral daily PrEP every day and/or after a sexual act, 542 (68.8%) were successfully contacted, 433 (54.9%) scheduled an appointment, 409 (51.9%) attended a scheduled appointment, 400 (50.8%) initiated oral daily PrEP, and 59 (7.4%) had protective levels of tenofovir disoproxil fumarate. Of initiators of PrEP, 23 (5.8%) seroconverted at a rate of 13.9 cases/100 person-years. Better social support, larger network density, and higher education were associated with engagement in 4 to 5 components of the cascade. CONCLUSIONS: Our data highlight a gap between willingness and actual PrEP use. Despite PrEP's effectiveness in preventing HIV, the optimal impact of PrEP for SGMs in sub-Saharan Africa will require multifaceted approaches that combine social support, education, and destigmatization.

The quality of life among men who have sex with men (MSM) living with and those not living with HIV in Abuja Nigeria.

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.

Prevalence of HIV drug resistance in Nigeria: results from a cross-sectional, population-based survey of Nigerian adults with unsuppressed viral load.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Individual and partnership characteristics associated with consistent condom use in a cohort of cisgender men who have sex with men and transgender women in Nigeria.

BACKGROUND: This study reports on the individual and partnership characteristics that influence consistent condom use in cisgender men who have sex with men (MSM) and transgender women (TGW) attending trusted community centers that provide HIV prevention and treatment services in Nigeria. METHODS: Adults assigned male at birth who reported anal sex with male partners who enrolled between March 2013-2019 and had information about at least one male sexual partner were included in these analyses. At enrollment and follow-up visits every 3 months for up to 18 months, participants were administered detailed questionnaires that collected information about demographics, sexual practices, HIV risk behaviors, and characteristics and behaviors of their partners in the previous year (at enrollment) or the preceding 3 to 6-months (at follow-up visits). Logistic regression models with generalized estimating equations were used to assess the odds ratio (OR) and 95% confidence intervals (CI) of individual, partner, and partnership characteristics associated with consistent condom use (CCU). A participant was defined as consistently using condom if they reported always using condoms all the time they had insertive, receptive or both types of anal sex with a male partner. RESULTS: At the individual level, CCU was positively associated with higher education, disclosure of key population status to a healthcare worker and negatively associated with poor access to condoms. At the partner and partnership level, CCU was associated with partners with higher education (aOR: 1.36; 95% CI: 1.07-1.72), casual relationships (aOR: 1.22; 95% CI: 1.11-1.34) and relationships in which partners encouraged the participant to use condoms with other partners (aOR: 1.14; 95% CI: 1.02-1.28). Relationships in which the partner was married to a woman and/or the partner's HIV status positive or unknown were negatively associated with CCU. CONCLUSIONS: These findings suggest that individuals in relationships where partners were more open and encouraged safer sex were more likely to consistently use condoms. HIV prevention programs should consider leveraging communication to sexual partners to encourage condom use as this may support condom use with other sexual partners. Given sustained and growing HIV and STI epidemics among MSM and TGW, even with pre-exposure prophylaxis scale-up, it is crucial to continue to study optimal implementation strategies to increase condom use.

Oral sex practices among men who have sex with men and transgender women at risk for and living with HIV in Nigeria.

BACKGROUND: Men who have sex with men (MSM) and transgender women (TGW) are at risk for sexually transmitted infections (STIs), including those of the oropharynx. We estimated the prevalence and factors associated with oral sex practices and characterized oropharyngeal STIs among a cohort of MSM and TGW in Nigeria. METHODS: From 2013 to 2018, TRUST/RV368 recruited MSM and TGW into HIV/STI diagnosis and treatment at community-based clinics in Nigeria. Participants who completed HIV testing and oral sex questions at enrollment were selected. Cross-sectional analyses with bivariate and multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs). Oropharyngeal swab testing for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) began in 2014 and for those with diagnostic results at enrollment, the unadjusted association of oral sex practices with oropharyngeal STIs was conducted. RESULTS: A total of 1342 participants had a median age of 25 years (interquartile range: 22-29), 58% were living with HIV, and 69% reported oral sex practices. Factors associated with increased odds of engaging in oral sex included living with HIV (adjusted [a]OR: 1.4, 95% CI: 1.1-1.8), self-identifying as a woman (aOR:1.8, 95% CI: 1.1-2.8), mobile phone ownership (aOR:2.3, 95% CI: 1.3-3.9), receptive anal sex (aOR:1.7, 95% CI:1.3-2.3) and multiple male sexual partners (2 to 4 vs. ≤1, aOR:1.5, 95% CI: 1.0-2.2; 5+ vs ≤1, aOR:2.9, 95% CI:1.9-4.3). Oropharyngeal STI prevalence was 7% (52/752) and higher among those who engaged in oral sex compared to those who did not (unadjusted OR: 2.5, 95% CI:1.2-5.3). CONCLUSIONS: Oral sex was common and associated with an increased odds of oropharyngeal STIs among MSM and TGW from Nigeria. In the absence of screening and treatment guidelines, condoms continue to be the mainstay for oral STI prevention. A pre-exposure prophylaxis for bacterial STIs would complement current prevention strategies to curb transmission.

High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment.

OBJECTIVES: HIV-1 integrase inhibitors are recommended as first-line therapy by WHO, though efficacy and resistance data for non-B subtypes are limited. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa. METHODS: We studied a Nigerian cohort of recipients prior to and during receipt of second-line PI-based therapy, who were integrase inhibitor-naive. Illumina next-generation sequencing with target enrichment was used on stored plasma samples. Drug resistance was interpreted using the Stanford Resistance Database and the IAS-USA 2019 mutation lists. RESULTS: Of 115 individuals, 59.1% harboured CRF02_AG HIV-1 and 40.9% harboured subtype G HIV-1. Four participants had major IAS-USA integrase resistance-associated mutations detected at low levels (2%-5% frequency). Two had Q148K minority variants and two had R263K (one of whom also had L74I). L74I was detected in plasma samples at over 2% frequency in 40% (46/115). Twelve (26.1%) had low-level minority variants of between 2% and 20% of the viral population sampled. The remaining 34 (73.9%) had L74I present at >20% frequency. L74I was more common among those with subtype G infection (55.3%, 26/47) than those with CRF02_AG infection (29.4%, 20/68) (P = 0.005). CONCLUSIONS: HIV-1 subtypes circulating in West Africa appear to have very low prevalence of major integrase mutations, but significant prevalence of L74I. A combination of in vitro and clinical studies is warranted to understand the potential implications.

Characterizing Cross-Culturally Relevant Metrics of Stigma Among Men Who Have Sex With Men Across 8 Sub-Saharan African Countries and the United States.

Overcoming stigma affecting gay, bisexual, and other men who have sex with men (MSM) is a foundational element of an effective response to the human immunodeficiency virus (HIV) pandemic. Quantifying the impact of stigma mitigation interventions necessitates improved measurement of stigma for MSM around the world. In this study, we explored the underlying factor structure and psychometric properties of 13 sexual behavior stigma items among 10,396 MSM across 8 sub-Saharan African countries and the United States using cross-sectional data collected between 2012 and 2016. Exploratory factor analyses were used to examine the number and composition of underlying stigma factors. A 3-factor model was found to be an adequate fit in all countries (root mean square error of approximation = 0.02-0.05; comparative fit index/Tucker-Lewis index = 0.97-1.00/0.94-1.00; standardized root mean square residual = 0.04-0.08), consisting of "stigma from family and friends," "anticipated health-care stigma," and "general social stigma," with internal consistency estimates across countries of α = 0.36-0.80, α = 0.72-0.93, and α = 0.51-0.79, respectively. The 3-factor model of sexual behavior stigma cut across social contexts among MSM in the 9 countries. These findings indicate commonalities in sexual behavior stigma affecting MSM across sub-Saharan Africa and the United States, which can facilitate efforts to track progress on global stigma mitigation interventions.

Metabolic Changes in Chronic Hepatitis C Patients Who Carry IFNL4-ΔG and Achieve Sustained Virologic Response With Direct-Acting Antiviral Therapy.

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.

Immunological recovery in T-cell activation after sustained virologic response among HIV positive and HIV negative chronic Hepatitis C patients.

BACKGROUND: Rapid decreases in activated CD4+ and CD8+ (HLA-DR + and CD38+ co-expressed) T-lymphocytes have been described within 1-2 weeks of initiating direct-acting antiviral (DAA) therapy among chronic Hepatitis C (CHC) patients. However, it is not known whether these changes are maintained past sustained virologic response (SVR), particularly in those who are HIV/HCV-coinfected. METHODS: We investigated the changes in immune parameters of T-lymphocytes from pre-DAA therapy to post-SVR among HIV negative and HIV positive patients with CHC. Repeated measurements of activated CD4+ and CD8+ T cells were analyzed by flow cytometry at pre-DAA therapy, DAA therapy, end of treatment, SVR, and post-SVR. A general linear model for repeated measurements was used to estimate the mean outcome at each timepoint and change between timepoints. RESULTS: HCV-monoinfected (n = 161) and HIV/HCV-coinfected (n = 59) patients who achieved SVR with DAA therapy were predominately middle aged, male, black, and non-cirrhotic. At pre-DAA therapy, HCV-monoinfected patients had significantly higher CD4+ T cells and CD4+:CD8+ T-cell ratio, while significantly lower CD8+ and activated CD4+ and CD8+ T cells compared to HIV/HCV-coinfected patients (p < 0.0001). HCV-monoinfected and HIV/HCV-coinfected patients had a significant mean decrease from pre-DAA therapy to post-SVR year 1 for activated CD4+ (HCV-monoinfected: 4.8-3.9%, p < 0.0001; HIV/HCV-coinfected: 6.6-4.5%, p < 0.0001) and activated CD8+ T cells (HCV-monoinfected V: 13.8-11.8%, p = 0.0002; HIV/HCV-coinfected: 18.0-12.4%, p < 0.0001). CONCLUSION: This longitudinal study showed CHC patients treated with DAA therapy had continued decrease of T-lymphocytes from start of DAA therapy to after achievement of SVR suggesting improvement as HCV clearance normalizes activated T-cell phenotype.

Health Workers' Perspectives on the Outcomes, Enablers, and Barriers to the Implementation of HIV "Test and Treat" Guidelines in Abuja, Nigeria.

We evaluated health workers' perspectives on the implementation of the 2016 HIV "Test and Treat" guidelines in Nigeria. Using semi-structured interviews, qualitative data was collected from twenty health workers meeting inclusion criteria in six study sites. Data exploration was conducted using thematic content analysis. Participants perceived that the "Test and Treat" guidelines improved care for PLHIV, though they also perceived possible congested clinics. Perceived key factors enabling guidelines use were perceived patient benefits, availability of policy document and trainings. Perceived key barriers to guidelines use were poverty among patients, inadequate human resources and stock-outs of HIV testing kits. Further improvements in uptake of guidelines could be achieved by effecting an efficient supply chain system for HIV testing kits, and improved guidelines distribution and capacity building prior to implementation. Additionally, implementing differentiated approaches that decongest clinics, and programs that economically empower patients, could improve guidelines use, as Nigeria scales "Test and Treat" nationwide.

Anal Microbial Patterns and Oncogenic Human Papillomavirus in a Pilot Study of Nigerian Men Who Have Sex with Men at Risk for or Living with HIV.

To cluster anal microbiota and define microbial patterns associated with biological, clinical, and behavioral correlates among Nigerian men who have sex with men (MSM) living with or at risk for HIV. In this cross-sectional pilot study, the 15 most abundant 16S taxa in the anal microbiota of 113 MSM underwent unsupervised K-means clustering and z-score comparisons to define similarities and dissimilarities among 4 microbiota taxonomic profiles. Distributions of oncogenic HPV (high-risk human papillomavirus [HR-HPV]), concurrent HIV, antiretroviral therapy (ART), and other clinical and behavioral data were evaluated using Fisher's exact and Kruskal-Wallis tests to determine biological signatures of cluster membership. Prevotella was consistently represented in each cluster, but the average composition ranged from 14% to 44%. Cluster 2 was enriched with a member of the Fusobacteria phylum, Sneathia (29%). More participants of cluster 2 were HIV infected and taking ART (83%, 5/6), were virally suppressed (80%, 4/5), had HPV-16 (66.7%, 4/6), and reported no vaginal sex partners (83%, 5/6). HPV-35, a highly prevalent oncogenic HPV in Nigeria, was observed in all clusters except cluster 2 (0%, 0/6). Other covariates were similar across clusters (all p > .05). K-means unsupervised clustering, a canonical pattern recognition method, generalized the microbial community composition and structure while accounting for among sample variability. Further studies are needed to evaluate whether an anal microbial community enriched with members of the Fusobacteria phylum is associated with HIV-infected MSM who are virally suppressed and have a concurrent HPV-16.

Mycoplasma promotes malignant transformation in vivo, and its DnaK, a bacterial chaperone protein, has broad oncogenic properties.

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.

Individual and Network Factors Associated With HIV Care Continuum Outcomes Among Nigerian MSM Accessing Health Care Services.

BACKGROUND AND SETTING: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Sexual partner characteristics and incident rectal Neisseria gonorrhoeae and Chlamydia trachomatis infections among gay men and other men who have sex with men (MSM): a prospective cohort in Abuja and Lagos, Nigeria.

BACKGROUND: STIs including Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) potentiate HIV acquisition and transmission especially among gay men and other men who have sex with men (MSM). We investigated the influence of sexual network composition on incident rectal NG and/or CT infections among Nigerian MSM. METHODS: TRUST/RV368 is a cohort of MSM recruited using respondent-driven sampling at trusted community centres in Abuja and Lagos, Nigeria. MSM respondents (egos) provided STI risk factors and demographic information for up to five of their most recent sexual partners (alters) within their sexual networks. Egos were tested for HIV, NG and CT every 3 months. Log-binomial regression was used to assess associations between alter characteristics and incident NG and/or CT. RESULTS: Between March 2013 and October 2015, 492 MSM were longitudinally screened for STIs, of which 28.0% (n=138) were positive for incident rectal STI (61 NG only, 42 CT only and 35 NG and CT). Among egos, condom use was associated with STIs (half of the time vs never (adjusted risk ratio (aRR) 0.5; 95% CI 0.3 to 0.8), always/almost always vs never (aRR 0.7; 95% CI 0.5 to 1.0)). Incident STIs were associated with having a younger alter ≤19 versus 30 years (aRR 0.6; 95% CI 0.4 to 1.0), HIV infection (aRR 1.5; 95% CI 1.1 to 2.0) and engaging in sex under the influence of alcohol (aRR 1.4 95% CI 1.1 to 1.7) among regular alters and age ≤19 versus 30 years (aRR 0.3; 95% CI 0.2 to 0.6), HIV infection (aRR 1.4; 95% CI 1.1 to 1.8) and engaging in sex under the influence of alcohol (aRR 1.2 95% CI 1.0 to 1.4) among casual alters. CONCLUSIONS: Given the centrality of sexual partner characteristics as risks for incident STIs among Nigerian MSM, there is a need to move beyond individual interventions and syndromic surveillance and get 'out there' in the STI management.

Socio-Demographic and Adherence Factors Associated with Viral Load Suppression in HIV-Infected Adults Initiating Therapy in Northern Nigeria: A Randomized Controlled Trial of a Peer Support Intervention.

BACKGROUND: Virological suppression is the main goal of antiretroviral therapy. To achieve this goal, efficient interventions that promote treatment adherence are needed. This study was aimed at exploring the impact of peer-education on virological outcomes in Northern Nigeria. METHODS: A randomized controlled trial (RCT) among patients receiving antiretroviral treatment was conducted in 2 phases between August 2006 and January 2008 in the "largely Muslim" Northern Nigeria. Participants were randomized into one of three intervention arms: standard of care arm, a second arm which included daily reminders via alarm and follow-up calls from peer-educators, and adherence support by a home-based treatment partner; and a third arm which included second arm activities, plus home visits by peer-educators. We evaluated sociodemographic factors and adherence levels, measured using self-report and pharmacy (Rx) refill rates, as risk factors for viral load (VL) suppression. RESULTS: Of the 600 participants (43% males), 276 were observed till the end of the study. There were no significant differences in mean log 10 VL between the intervention groups. At the end of entire follow-up period, 83% (229/276) who were not lost to follow-up achieved undetectable VL (< 400 copies/ml). In the multivariable analysis, age between 30-34 years (vs 18-24 years) and both baseline CD4 ranges between 100-199 cells/mm(3) or 200-349 cells/mm(3) (vs CD4 <100 cells/mm(3)) as positively associated with VL suppression while poor self-reported adherence and <95% Rx refill rates were negatively associated with VL suppression. CONCLUSION: High levels of viral suppression and low prevalence of drug resistance mutations (DRMs) were seen in this cohort participating in an ART adherence study in Northern Nigeria. Self-reported good adherence and optimal Rx refill rates were reported as significant predictors of VL suppression. Our findings indicate that ART adherence will improve significantly regardless of whether HIV-infected adults received peer-education-based medication adherence interventions or standard of care services.