Evaluating the Jaccard Similarity Index as a Persistence Measure of Multiple Anal Human Papillomavirus Among Nigerian Men Who Have Sex With Men.

BACKGROUND: Multiple anal human papillomavirus (HPVs) may increase the risk of anal cancer among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). The Jaccard Similarity Index (JSI) was explored as a measure of multiple HPV persistence. METHODS: The TRUST/RV368 cohort enrolled MSM living with and without HIV in Abuja and Lagos, Nigeria. Participants with anal swabs at baseline, 3- and 12-month visits were tested for high- and low-risk HPVs using a next-generation sequencing assay. Persistence of the same HPV genotypes over time was calculated using the JSI and categorized into high, medium, and low similarity tertiles. Factors associated with higher versus lower similarity were estimated with multivariable ordinal logistic regression and reported as adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Of the 225 participants, median age was 25 years (interquartile range, 22-29 years), 62% were living with HIV, median HPVs was 3 (interquartile range, 2-5), and HPV6 (28%), HPV16 (26%), HPV11 (23%), and HPV45 (20%) were most prevalent. Fifty-three percent of participants had highly similar HPVs at 3 months, and the similarity was associated with HIV (aOR, 3.11; 95% CI, 1.6-5.9) and recent receptive sex (aOR, 1.9; 95% CI, 1.0-3.5). By 12 months, 20% had highly similar HPVs, and it was associated with 12 years or longer since anal coital debut (aOR, 6.8; 95% CI, 3.1-5.2), self-reported genital warts (aOR, 3.1; 95% CI, 1.5-6.6), and 200 or less CD4 cells/mm3 (aOR, 13.3; 95% CI, 2.7-65.2) for those living with HIV. CONCLUSIONS: Studies evaluating the JSI as a predictor of high-grade intraepithelial lesions would further confirm its applicability as a quantitative measure of multiple HPV persistence.

Elevated Plasma Levels of sCD14 and MCP-1 Are Associated With HIV Associated Neurocognitive Disorders Among Antiretroviral-Naive Individuals in Nigeria.

BACKGROUND: Mononuclear cells play key roles in the pathogenesis of HIV-associated neurocognitive disorders (HAND). Limited studies have looked at the association of markers of monocyte activation with HAND in Africa. We examined this association among HIV-1-infected patients in Nigeria. METHOD: A total of 190 HIV-infected treatment-naive participants with immune marker data were included in this cross-sectional study. Plasma levels of soluble CD14 (sCD14), soluble CD163, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and neopterin were measured. Demographically adjusted T scores obtained from a 7-domain neuropsychological test battery were generated, and functional status was assessed using activities of daily living questionnaire. Participants were classified as unimpaired, having asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD) in line with the "Frascati" criteria. RESULTS: Thirty-two participants (16.8%) had ANI, 14 (7.4%) had MND, whereas none had HAD. In multivariable linear regression analyses, after adjusting for age, gender, education, CD4 count, and viral load, mean levels of sCD14 were higher among those with ANI and MND as compared with the unimpaired (P = 0.033 and 0.023, respectively). Similarly, the mean level of MCP-1 was greater among those with HAND as compared with the unimpaired (P = 0.047). There were also trends for higher levels of sCD163 and TNF-α among females with MND in univariable analyses. CONCLUSIONS: Levels of monocyte activation markers correlate with the severity of impairment among individuals with HAND. The mechanisms that underlie these effects and the potential role of gender require further study.

Implementation of and Early Outcomes From Anal Cancer Screening at a Community-Engaged Health Care Facility Providing Care to Nigerian Men Who Have Sex With Men.

PURPOSE: Anal cancer risk is substantially higher among HIV-infected men who have sex with men (MSM) as compared with other reproductive-age adults, but screening is rare across sub-Saharan Africa. We report the use of high-resolution anoscopy (HRA) as a first-line screening tool and the resulting early outcomes among MSM in Abuja, Nigeria. METHODS: From August 2016 to August 2017, 424 MSM enrolled in an anal cancer screening substudy of TRUST/RV368, a combined HIV prevention and treatment cohort. HRA-directed biopsies were diagnosed by histology, and ablative treatment was offered for high-grade squamous intraepithelial lesions (HSIL). HRA proficiency was assessed by evaluating the detection of squamous intraepithelial lesions (SIL) over time and the proportion biopsied. Prevalence estimates of low-grade squamous intraepithelial lesions and HSIL with 95% CIs were calculated. Multinomial logistic regression was used to identify those at the highest risk of SIL. RESULTS: Median age was 25 years (interquartile range [IQR], 22-29), median time since sexual debut was 8 years (IQR, 4-12), and 59% (95% CI, 54.2% to 63.6%) were HIV infected. Rate of detection of any SIL stabilized after 200 screenings, and less than 20% had two or more biopsies. Preliminary prevalence estimates of low-grade squamous intraepithelial lesions and HSIL were 50.0% (95% CI, 44.7% to 55.3%) and 6.3% (95% CI, 4.0% to 9.3%). HIV infection, at least 8 years since anal coital debut, concurrency, and external warts were independently statistically associated with SIL. CONCLUSION: Proficiency with HRA increased with experience over time. However, HSIL detection rates were low, potentially affected by obstructed views from internal warts and low biopsy rates, highlighting the need for ongoing evaluation and mentoring to validate this finding. HRA is a feasible first-line screening tool at an MSM-friendly health care facility. Years since anal coital debut and external warts could prioritize screening.

Individual and Sexual Network Predictors of HIV Incidence Among Men Who Have Sex With Men in Nigeria.

BACKGROUND: To date, HIV incidence studies among men who have sex with men (MSM) across sub-Saharan Africa have focused on studying sexual risk practices with less focus on sexual networks. SETTING: TRUST/RV368 conducted in Abuja and Lagos, Nigeria, recruited MSM using respondent-driven sampling and followed HIV-negative men for incident infection over 4 years. METHODS: Four-hundred forty-one HIV-uninfected MSM underwent a parallel rapid HIV testing algorithm every 3 months for up to 18 months. HIV incidence per 100 person-years (PY) and 95% confidence intervals (CIs) were estimated using Poisson regression. Individual and network characteristics were examined using multivariable Cox-proportional hazards regression adjusted and unadjusted for respondent-driven sampling weights. RESULTS: Among cohort members with a median age of 23 years [interquartile range (IQR): 20-27], 81 HIV infections occurred over 527 PY (incidence 15.4/100 PY; 95% CI: 12.3 to 19.0). The incidence rate was highest among 16-19 year olds as compared to those 25 years or older (30.9/100 PY; 95% CI: 22.1 to 45.3 vs. 6.9/100 PY; 95% CI: 4.2 to 10.9, respectively). Individual determinants included receptive partnerships, condomless sex, no history of testing for HIV, and rectal gonorrhea. Sexual networks were larger and consisted of an older sexual partner, although there was no clustering by recruitment networks. CONCLUSIONS: These HIV incidence data reinforce the unmet HIV prevention needs among young MSM in Nigeria. Even in the context of emerging HIV diagnostic and prevention strategies, structural challenges including stigma and criminalization of same-sex practices highlight the need for novel implementation approaches in the context of MSM-friendly services.

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.

Brief Report: Body Mass Index and Cognitive Function Among HIV-1-Infected Individuals in China, India, and Nigeria.

BACKGROUND: Risk of cognitive impairment is increased among persons with high or low body mass index in HIV- and HIV+ populations in resource-rich settings. We examined this association among HIV+ patients in 3 resource-limited settings. METHODS: This secondary analysis included data of 761 HIV+ volunteers pooled from 3 prospective cohort studies conducted in China (n = 404; 53%), India (n = 200; 26%), and Nigeria (n = 157; 21%). World Health Organization (WHO) weight classifications were based on body mass index. T scores, adjusted for demographics and practice effects, were derived from a 7-domain neuropsychological battery. Neurocognitive impairment (NCI) was defined as global deficit score of ≥0.5. RESULTS: Overall, prevalence of NCI at baseline was 27.7% (similar across all cohorts). The overweight/obese and underweight constituted 37.3% and 15.5% of the total participants, respectively. In a multivariable logistic regression of pooled longitudinal data, adjusting for clinical and demographic variables, the odds of global NCI were 38% higher among the overweight/obese as compared to normal weight participants [odds ratio: 1.38 (95% confidence interval: 1.1 to 1.72); P = 0.005]. Similarly, the odds of global NCI were 39% higher among the underweight as compared to normal weight participants [odds ratio: 1.39 (95% confidence interval: 1.03 to 1.87); P = 0.029]. CONCLUSIONS: NCI among HIV-1-infected patients was more prevalent in both overweight/obese and underweight than normal weight individuals in 3 resource-limited settings, confirming observations in resource-rich settings. Mechanisms underlying these associations are unclear but likely differ for underweight and overweight persons.

Plasma HIV RNA level is associated with neurocognitive function among HIV-1-infected patients in Nigeria.

Plasma HIV RNA level has been shown to correlate with HIV disease progression, morbidity, and mortality. We examined the association between levels of plasma HIV RNA and cognitive function among patients in Nigeria. A total of 179 HIV-1-infected participants with available plasma HIV RNA results and followed longitudinally for up to 2 years were included in this study. Blood samples from participants were used for the measurement of plasma HIV RNA and CD4+ T cell count. Utilizing demographic and practice effect-adjusted T scores obtained from a seven-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS ≥ 0.5 indicating cognitive impairment. In a longitudinal multivariable linear regression analysis, adjusting for CD4 cell count, Beck's Depression Score, age, gender, years of education, and antiretroviral treatment status, global T scores decreased by 0.35 per log10 increase in plasma HIV RNA [p = 0.033]. Adjusting for the same variables in a multivariable logistic regression, the odds of neurocognitive impairment were 28% higher per log10 increase in plasma HIV RNA (OR 1.28 [95% CI 1.08, 1.51]; p = 0.005). There were statistically significant associations for the speed of information processing, executive, and verbal fluency domains in both linear and logistic regression analyses. We found a significant association between plasma HIV RNA levels and cognitive function in both baseline (cross-sectional) and longitudinal analyses. However, the latter was significantly attenuated due to weak association among antiretroviral-treated individuals.

Cognitive Function Among Antiretroviral Treatment-Naive Individuals Infected With Human Immunodeficiency Virus Type 1 Subtype G Versus CRF02_AG in Nigeria.

Background: Human immunodeficiency virus type 1 (HIV-1) subtype has been shown to be associated with disease progression. We compared cognitive function between individuals infected with HIV-1 subtype G and CRF02_AG in Nigeria. Methods: For this cross-sectional study, samples were analyzed from 146 antiretroviral-naive participants. Genotypic analysis of plasma HIV RNA was performed by nested polymerase chain reaction of protease and reverse transcriptase genes, and sequences were aligned with curated HIV-1 subtype references. Cognitive status was determined using demographically adjusted T scores and global deficit score (GDS) obtained from a comprehensive neuropsychological test battery. Results: A total of 76 (52.1%) participants were infected with CRF02_AG, 48 (32.8%) with subtype G, and 22 (15.1%) with other HIV-1 strains. In a multivariable linear regression adjusting for plasma HIV RNA, CD4 count, and depression score, mean global T score was lower among subtype G-infected compared with CRF02_AG-infected participants (mean difference, -3.0 [95% confidence interval {CI}, -5.2, to -.7]; P = .011). Also, T scores were significantly lower among subtype G- than CRF02_AG-infected participants for the speed of information processing, executive function, and verbal fluency ability domains. Adjusting for similar variables in a logistic regression, the odds of global cognitive impairment (GDS ≥0.5) were 2.2 times higher among subtype G compared with CRF02_AG-infected participants (odds ratio, 2.2 [95% CI, .9-5.4]; P = .078). Conclusions: Cognitive performance was significantly worse among antiretroviral-naive individuals with HIV-1 subtype G vs CRF02_AG infection. Further studies are required to characterize the mechanistic basis for these differences.

Phylodynamic analysis to inform prevention efforts in mixed HIV epidemics.

In HIV epidemics of Sub Saharan Africa, the utility of HIV prevention efforts focused on key populations at higher risk of HIV infection and transmission is unclear. We conducted a phylodynamic analysis of HIV-1 pol sequences from four different risk groups in Abuja, Nigeria to estimate transmission patterns between men who have sex with men (MSM) and a representative sample of newly enrolled treatment naive HIV clients without clearly recorded HIV acquisition risks. We develop a realistic dynamical infectious disease model which was fitted to time-scaled phylogenies for subtypes G and CRF02_AG using a structured-coalescent approach. We compare the infectious disease model and structured coalescent to commonly used genetic clustering methods. We estimate HIV incidence among MSM of 7.9% (95%CI, 7.0-10.4) per susceptible person-year, and the population attributable fraction of HIV transmissions from MSM to reproductive age females to be 9.1% (95%CI, 3.8-18.6), and from the reproductive age women to MSM as 0.2% (95%CI, 0.06-0.3). Applying these parameter estimates to evaluate a test-and-treat HIV strategy that target MSM reduces the total HIV infections averted by half with a 2.5-fold saving. These results suggest the importance of addressing the HIV treatment needs of MSM in addition to cost-effectiveness of specific scale-up of treatment for MSM in the context of the mixed HIV epidemic observed in Nigeria.

Stigma, access to healthcare, and HIV risks among men who sell sex to men in Nigeria.

INTRODUCTION: Among men who have sex with men (MSM), men who sell sex (MSS) may be subject to increased sexual behaviour-related stigma that affects uptake of healthcare and risk of sexually transmitted infections (STIs). The objectives of this study were to characterize stigma, access to care, and prevalence of HIV among MSS in Nigeria. METHODS: Respondent-driven sampling was used to recruit MSM in Abuja and Lagos into the ongoing TRUST/RV368 study, which provides HIV testing and treatment. Detailed behavioural data were collected by trained interviewers. MSS were identified by self-report of receiving goods or money in exchange for sex with men. Poisson regression with robust error variance was used to explore the impact of sex-selling on the risk of HIV. RESULTS: From 12 initial seed participants, 1552 men were recruited from March 2013-March 2016. Of these, 735 (47.4%) reported sex-selling. Compared to other MSM, MSS were younger (median 22 vs. 24 years, p < 0.001) and more likely to identify as gay/homosexual (42.4% vs. 31.5%, p < 0.001). MSS were more likely to report perceived and experienced stigmas such as healthcare avoidance (27.6% vs. 21.5%, p = 0.005) and verbal harassment (39.2% vs. 26.8%, p < 0.001). Total HIV prevalence was 53.4%. After controlling for other factors, HIV prevalence among MSS was similar to that observed among other MSM (relative risk 0.94 [95% confidence interval 0.84-1.05]). CONCLUSION: These data highlight increased sexual behaviour-related stigma affecting MSS, as compared with other MSM, that limits uptake of healthcare services. The distinct characteristics and risks among MSS suggest the need for specific interventions to optimize linkage to HIV prevention and treatment services in Nigeria.

Peripheral blood lymphocyte HIV DNA levels correlate with HIV associated neurocognitive disorders in Nigeria.

Mononuclear cells play key roles in the pathogenic mechanisms leading to HIV-associated neurocognitive disorders (HANDs). We examined the association between HIV DNA within peripheral blood mononuclear cell (PBMC) subsets and HAND in Nigeria. PBMCs were collected at baseline from 36 antiretroviral naive participants. CD14+ cells and T&B lymphocyte fractions were isolated by, respectively, positive and negative magnetic bead separation. Total HIV DNA within CD14+ and T&B cells were separately quantified using real-time PCR assay targeting HIV LTR-gag and cell input numbers determined by CCR5 copies/sample. Utilizing demographically adjusted T scores obtained from a 7-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS of ≥0.5 indicating cognitive impairment. In a linear regression adjusting for plasma HIV RNA, CD4 and lymphocyte count, Beck's depression score, and years of education, there was 0.04 lower log10 HIV DNA copies within T&B lymphocytes per unit increase in global T score (p = 0.02). Adjusting for the same variables in a logistic regression, the odds of cognitive impairment were 6.2 times greater per log10 increase in HIV DNA within T&B lymphocytes (p = 0.048). The association between cognitive impairment and HIV DNA within CD14+ monocytes did not reach statistical significance. In this pretreatment cohort with mild cognitive dysfunction, we found a strong association between levels of HIV DNA within the lymphocyte subset and HAND independent of plasma HIV RNA. These findings likely reflect the neurologic impact of a larger HIV reservoir and active viral replication.

Rectal microbiota among HIV-uninfected, untreated HIV, and treated HIV-infected in Nigeria.

OBJECTIVE: Untreated advanced HIV infection alters the gut microbiota, but it is unclear whether antiretroviral therapy (ART) reverses these changes. We compared the composition of the rectal microbiota among three groups of men who have sex with men (MSM): HIV-uninfected, untreated HIV, and ART-treated HIV-infected. DESIGN: A cross-sectional study was conducted among 130 MSM (55 HIV-uninfected, 41 untreated HIV, and 34 ART-treated HIV) in Abuja, Nigeria. METHODS: Bacterial 16S rRNA genes were amplified from rectal swabs, sequenced and clustered into Genera-level operational taxonomic units. Alpha diversity was quantified using the Shannon index and compared among groups using the Kruskal-Wallis test; associations with other scale variables were quantified using Spearman's rank correlation (Rs). The relative abundance of the top 15 taxa was compared according to HIV infection/treatment status using the Wilcoxon rank sum test. RESULTS: HIV-treated MSM had a decrease in a commensal phylum, Bacteroidetes (P < 0.01). Alpha diversity was positively correlated with viral loads (Rs = 0.32, P < 0.01). Statistically significant shifts in relative abundance of rectal microbiota for the HIV-treated group included a decrease in the most abundant bacteria, Prevotella (P = 0.02) and an increase in pathogenic bacteria, Peptoniphilus (P = 0.04), Finegoldia (P = 0.01), Anaerococcus (P = 0.03), and Campylobacter (P = 0.03) compared with the other groups. CONCLUSION: Untreated HIV infection does not significantly alter the rectal microbiota, whereas prior treatment is associated with a shift toward a more pathogenic pattern of microbiota. Treatment with an antibiotic, co-trimoxazole, in conjunction with ART may have contributed to this shift.

Online Sex-Seeking Among Men who have Sex with Men in Nigeria: Implications for Online Intervention.

The TRUST/RV368 project was undertaken to apply innovative strategies to engage Nigerian MSM into HIV care. In this analysis we evaluate characteristics of online sex-seekers from the TRUST/RV368 cohort of 1370 MSM in Abuja and Lagos. Logistic regression and generalized estimating equation models were used to assess associations with online sex-seeking. Online sex-seeking (n = 843, 61.5 %) was associated with participation in MSM community activities, larger social and sexual networks, and higher levels of sexual behavior stigma. In addition, online sex-seeking was associated with testing positive for HIV at a follow-up visit [adjusted odds ratio (aOR) = 2.02, 95 % confidence interval (CI) = 1.37, 2.98)] among those who were unaware of or not living with HIV at baseline. Across visits, online sex-seekers were marginally more likely to test positive for chlamydia/gonorrhea (aOR 1.28, 95 % CI 0.99, 1.64). Online sex-seekers in Nigeria are at increased risk for HIV/STIs but may not be benefiting from Internet-based risk reduction opportunities.

High prevalence of HIV, chlamydia and gonorrhoea among men who have sex with men and transgender women attending trusted community centres in Abuja and Lagos, Nigeria.

INTRODUCTION: Sexually transmitted infection (STI) and HIV prevalence have been reported to be higher amongst men who have sex with men (MSM) in Nigeria than in the general population. The objective of this study was to characterize the prevalence of HIV, chlamydia and gonorrhoea in this population using laboratory-based universal testing. METHODS: TRUST/RV368 represents a cohort of MSM and transgender women (TGW) recruited at trusted community centres in Abuja and Lagos, Nigeria, using respondent-driven sampling (RDS). Participants undergo a structured comprehensive assessment of HIV-related risks and screening for anorectal and urogenital Chlamydia trachomatis and Neisseria gonorrhoeae, and HIV. Crude and RDS-weighted prevalence estimates with 95% confidence intervals (CIs) were calculated. Log-binomial regression was used to explore factors associated with prevalent HIV infection and STIs. RESULTS: From March 2013 to January 2016, 862 MSM and TGW (316 in Lagos and 546 in Abuja) underwent screening for HIV, chlamydia and gonorrhoea at study enrolment. Participants' median age was 24 years [interquartile range (IQR) 21-27]. One-third (34.2%) were identified as gay/homosexual and 65.2% as bisexual. The overall prevalence of HIV was 54.9%. After adjusting for the RDS recruitment method, HIV prevalence in Abuja was 43.5% (95% CI 37.3-49.6%) and in Lagos was 65.6% (95% CI 54.7-76.5%). The RDS-weighted prevalence of chlamydia was 17.0% (95% CI 11.8-22.3%) in Abuja and 18.3% (95% CI 11.1-25.4%) in Lagos. Chlamydia infection was detected only at the anorectal site in 70.2% of cases. The RDS-weighted prevalence of gonorrhoea was 19.1% (95% CI 14.6-23.5%) in Abuja and 25.8% (95% CI 17.1-34.6%) in Lagos. Overall, 84.2% of gonorrhoea cases presented with anorectal infection only. Over 95% of STI cases were asymptomatic. In a multivariable model, increased risk for chlamydia/gonorrhoea was associated with younger age, gay/homosexual sexual orientation and higher number of partners for receptive anal sex. HIV infection was associated with older age, female gender identity and number of partners for receptive anal sex. CONCLUSIONS: There is a high burden of infection with HIV and asymptomatic chlamydia and gonorrhoea among MSM and TGW in Nigeria. Most cases would have been missed without anorectal screening. Interventions are needed to target this population for appropriate STI screening and management beginning at a young age.

Prevalence of Anal High-Risk Human Papillomavirus Infections Among HIV-Positive and HIV-Negative Men Who Have Sex With Men in Nigeria.

BACKGROUND: Prevalence estimates of anal high-risk human papillomavirus (HR-HPV) are needed in sub-Saharan Africa where HIV is endemic. This study evaluated anal HR-HPV in Nigeria among HIV-positive and HIV-negative men who have sex with men (MSM) for future immunization recommendations. METHODS: We conducted a cross-sectional study to compare the prevalence of anal HR-HPV infections between 64 HIV-negative and 90 HIV-positive MSM. Multivariate Poisson regression analyses were used to examine demographic and behavioral risk factors associated with any HR-HPV infections. RESULTS: The median age of the 154 participants was 25 years (interquartile range, 22-28 years; range, 16-38 years), and the median age at initiation of anal sex with another man was 16 years (interquartile range, 13-18 years; range, 7-29 years). The prevalence of anal HR-HPV was higher among HIV-positive than HIV-negative MSM (91.1% vs. 40.6%, P < 0.001). In the multivariate analysis, HIV infection (adjusted prevalence ratio [aPR], 2.02; 95% confidence interval [CI], 1.49-2.72), 10 years or more since anal sexual debut (aPR, 1.26; 95% CI, 1.07-1.49), and concurrent relationships with men (aPR, 1.32; 95% CI, 1.04-1.67) were associated with increased anal HR-HPV prevalence. CONCLUSIONS: Anal HR-HPV infection is high for young Nigerian MSM, and rates are amplified in those coinfected with HIV. Providing universal coverage as well as catch-up immunization for young MSM may be an effective anal cancer prevention strategy in Nigeria.

Associations between Cognition, Gender and Monocyte Activation among HIV Infected Individuals in Nigeria.

The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naïve seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes.

HIV-associated lymphoma sub-type distribution, immunophenotypes and survival in an urban clinic population.

HIV-infected patients have an increased risk for both Hodgkin and non-Hodgkin lymphomas. A retrospective cohort of all HIV-infected patients diagnosed with lymphoma in urban clinics from 2000-2013 was evaluated to characterize the distribution and determine effects of sub-type and immunophenotype on survival. Of 160 cases identified, 131 (82%) had complete information and were analyzed. The most common sub-types were diffuse large B cell (41%), Burkitt (21%) and Hodgkin lymphoma (18%). Advanced (78% stage III/IV) and extranodal disease (82%) at presentation were common. CD20 was the most commonly expressed immunophenotypic marker (89%). Overall mortality rate was high (26.1 per 100 person-years). Lower mortality was noted in CD10 + and CD20 + lymphomas, but differences were not statistically significant. After adjustment, low CD4 count (≤ 200) at diagnosis was associated with higher mortality (adjusted hazard ration (AHR) = 1.75; 95% CI = 1.00-3.61). Mortality in this cohort of patients with HIV-associated lymphomas was high and exceeds that from published data from the general population.

Role of HIV-1 matrix protein p17 variants in lymphoma pathogenesis.

Although in decline after successful anti-HIV therapy, B-cell lymphomas are still elevated in HIV-1-seropositive (HIV+) persons, and the mechanisms are obscure. The HIV-1 matrix protein p17 persists in germinal centers long after HIV-1 drug suppression, and some p17 variants (vp17s) activate Akt signaling and promote growth of transformed B cells. Here we show that vp17s derived from four of five non-Hodgkin lymphoma (NHL) tissues from HIV+ subjects display potent B-cell growth-promoting activity. They are characterized by amino acid insertions at position 117-118 (Ala-Ala) or 125-126 (Gly-Asn or Gly-Gln-Ala-Asn-Gln-Asn) among some other mutations throughout the sequence. Identical dominant vp17s are found in both tumor and plasma. Three of seven plasma samples from an independent set of NHL cases manifested multiple Ala insertions at position 117-118, and one with the Ala-Ala profile also promoted B-cell growth and activated Akt signaling. Ultradeep pyrosequencing showed that vp17s with C-terminal insertions are more frequently detected in plasma of HIV+ subjects with than without NHL. Insertion of Ala-Ala at position 117-118 into reference p17 (refp17) was sufficient to confer B-cell growth-promoting activity. In contrast, refp17 bearing the Gly-Asn insertion at position 125-126 did not, suggesting that mutations not restricted to the C terminus can also account for this activity. Biophysical analysis revealed that the Ala-Ala insertion mutant is destabilized compared with refp17, whereas the Gly-Asn form is stabilized. This finding provides an avenue for further exploration of structure function relationships and new treatment strategies in combating HIV-1-related NHL.

Analysis of reverse transcriptase and protease genes of HIV for antiretroviral drug resistance in treatment-exposed Jamaican pediatrics.

This study reports on the drug resistance profiles for HIV-infected pediatrics in Jamaica who have been exposed to antiretroviral therapy (ART). The genetic diversity of HIV-1 found in these patients was also determined using phylogenetic analysis. The protease-reverse transcriptase (Pro-RT) region of the genome was amplified from 40 samples, sequenced, and analyzed for the identification of antiretroviral resistance-associated mutations (RAMs). All isolates belonged to subtype B and 39 possessed multiple RAMs in the reverse transcriptase genes that would compromise the efficacy of drugs being used to treat these patients. Four isolates possessed RAMs in the protease genes. The overall frequency of HIV drug resistance was 95%. The high frequency of drug resistance is supported by epidemiological data that revealed an equally high frequency of treatment failure (98%) among the study participants. The results of this study indicate the urgent need for greater access to drug resistance testing in Jamaica.