In Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 Matrix.

Protease inhibitors (PIs) are the second- and last-line therapy for the majority of HIV-infected patients worldwide. Only around 20% of individuals who fail PI regimens develop major resistance mutations in protease. We sought to explore the role of mutations in gag-pro genotypic and phenotypic changes in viruses from six Nigerian patients who failed PI-based regimens without known drug resistance-associated protease mutations in order to identify novel determinants of PI resistance. Target enrichment and next-generation sequencing (NGS) with the Illumina MiSeq system were followed by haplotype reconstruction. Full-length Gag-protease gene regions were amplified from baseline (pre-PI) and virologic failure (VF) samples, sequenced, and used to construct gag-pro-pseudotyped viruses. Phylogenetic analysis was performed using maximum-likelihood methods. Susceptibility to lopinavir (LPV) and darunavir (DRV) was measured using a single-cycle replication assay. Western blotting was used to analyze Gag cleavage. In one of six participants (subtype CRF02_AG), we found 4-fold-lower LPV susceptibility in viral clones during failure of second-line treatment. A combination of four mutations (S126del, H127del, T122A, and G123E) in the p17 matrix of baseline virus generated a similar 4-fold decrease in susceptibility to LPV but not darunavir. These four amino acid changes were also able to confer LPV resistance to a subtype B Gag-protease backbone. Western blotting demonstrated significant Gag cleavage differences between sensitive and resistant isolates in the presence of drug. Resistant viruses had around 2-fold-lower infectivity than sensitive clones in the absence of drug. NGS combined with haplotype reconstruction revealed that resistant, less fit clones emerged from a minority population at baseline and thereafter persisted alongside sensitive fitter viruses. We used a multipronged genotypic and phenotypic approach to document emergence and temporal dynamics of a novel protease inhibitor resistance signature in HIV-1 matrix, revealing the interplay between Gag-associated resistance and fitness.

Secular trend in interobserver agreement of VIA diagnosis for cervical cancer screening in Nigeria.

OBJECTIVE: In low resource settings, visual inspection with acetic acid (VIA) by allied health workers, has been suggested as an alternative for cervical cancer screening. However, there are concerns about the objectivity and time to diagnostic concordance with specialists. We evaluated the secular trend in interobserver agreement between nurse providers and a gynecologist/colposcopist over a five-year period. METHODS: Nurses provided VIA screening with digital cervivography to 4,961 participants in five screening clinics from October 2010 to May 2014 in Nigeria in this observational study. Cervigraphs were reviewed at meetings where a gynaecologist/colposcopist made an assessment from the cervigraphs. We used weighted kappa statistics to calculate agreement in diagnosis between nurse providers and the gynecologist/colposcopist; linear regression models to examine overall trend and investigate potential clinic characteristics that may influence agreement; and time series models to characterize month to month variations. RESULTS: Mean age of participants was 37±8 years. Overall agreement was 0.89 at Site D, 0.78 and 0.73 at Sites A and C respectively, 0.50 for Site E and 0.34 for Site C. The number of trainings attended by nurse providers(ß = 0.47,95%CI:0.02-0.93, p = 0.04), high level of engagement by site gynecologists(ß = 0.11,95%CI:0.01-0.21,p = 0.04) were associated with increased agreement; while increasing distance from the coordinating site(ß = -0.47,95%CI:-0.92-0.02,p = 0.04) was associated with decreased agreement. There were no associations between number of years screening clinics were operational(ß = 0.01,95%CI: -0.01-0.03,p = 0.29), cumulative experience of nurse providers(ß = 0.04,95%CI:-0.03-0.12,p = 0.19) and agreement. There were no significant increases in weighted kappa statistics over time for all sites considered. Monthly variations were significant for only one of two sites considered in time series models (AR1 term = -0.40, 95%CI:-0.71-0.09,p = 0.01). CONCLUSION: Our results showed a lack of objectivity, persistent variation and lack of convergence of diagnostic capabilities of nurse led VIA cervical cancer screening with the diagnostic capabilities of a specialist in a cervical cancer screening program in Nigeria.

Depression, suicidality, and alcohol use disorder among people living with HIV/AIDS in Nigeria.

BACKGROUND: People Living with HIV/AIDS (PLHIV) face various day-to-day and long-term personal, interpersonal, social, physical and psychological challenges as a result of, and in addition to the health conditions they are susceptible to due to their HIV status. There is a dearth of large-scale research to provide robust prevalence estimates of mental health problems among PLHIV, especially in Nigeria. This study aimed to ascertain the prevalence and factors associated with major depressive episodes, suicidality, and alcohol use disorder among people living with HIV/AIDS in Nigeria. METHODS: A survey of 1187 participants aged 18 years and above was conducted within three HIV treatment centres in Abuja, Nigeria. Depression, suicidality, and alcohol use disorder modules of the WHO World Mental Health Composite International Diagnostic Interview questionnaire were used for this study. A socio-demographic questionnaire was also used to collect other health and demographic data. Descriptive statistics (frequency distribution, percentage, mean, median, mode, and standard deviation) and regression analyses were conducted to explore associations between mental health problems and demographic and other health-related factors. RESULTS: Twelve-month prevalence rates were 28.2% for major depressive episodes, 2.9% for suicidal ideation, 2.3% for suicide attempts, 7.8% for harmful alcohol use, 7.0% for alcohol abuse, and 2.2% for alcohol dependence. Major depressive episodes were significantly associated with having planned suicide and marital status. Suicidal ideation was significantly associated with major depressive episodes, marital status, and religion. Females were less likely to be diagnosed with alcohol disorders. CONCLUSIONS: Some people living with HIV/AIDS also tend to suffer from depression, suicidality, and alcohol use disorders. These findings highlight the need for the integration of mental health services into HIV/AIDS care in Nigeria.

Influence of Spirituality and Modesty on Acceptance of Self-Sampling for Cervical Cancer Screening.

INTRODUCTION: Whereas systematic screening programs have reduced the incidence of cervical cancer in developed countries, the incidence remains high in developing countries. Among several barriers to uptake of cervical cancer screening, the roles of religious and cultural factors such as modesty have been poorly studied. Knowledge about these factors is important because of the potential to overcome them using strategies such as self-collection of cervico-vaginal samples. In this study we evaluate the influence of spirituality and modesty on the acceptance of self-sampling for cervical cancer screening. METHODOLOGY: We enrolled 600 participants in Nigeria between August and October 2014 and collected information on spirituality and modesty using two scales. We used principal component analysis to extract scores for spirituality and modesty and logistic regression models to evaluate the association between spirituality, modesty and preference for self-sampling. All analyses were performed using STATA 12 (Stata Corporation, College Station, Texas, USA). RESULTS: Some 581 (97%) women had complete data for analysis. Most (69%) were married, 50% were Christian and 44% were from the south western part of Nigeria. Overall, 19% (110/581) of the women preferred self-sampling to being sampled by a health care provider. Adjusting for age and socioeconomic status, spirituality, religious affiliation and geographic location were significantly associated with preference for self-sampling, while modesty was not significantly associated. The multivariable OR (95% CI, p-value) for association with self-sampling were 0.88 (0.78-0.99, 0.03) for spirituality, 1.69 (1.09-2.64, 0.02) for religious affiliation and 0.96 (0.86-1.08, 0.51) for modesty. CONCLUSION: Our results show the importance of taking cultural and religious beliefs and practices into consideration in planning health interventions like cervical cancer screening. To succeed, public health interventions and the education to promote it must be related to the target population and its preferences.

Demographic predictors of HIV serostatus among HIV counseling and testing clients in rural Nigeria.

Nnewi is a rural Nigerian town with a human immunodeficiency virus (HIV) counseling and testing center which tests about 120 clients/d. The objective of this study is to determine the factors predicting positive HIV status at Nnewi. Review of records was done with age, gender, marital status, and occupation as variables. Logistic regression analysis was used to identify factors linked to a positive HIV test. Overall HIV prevalence was 31.14%. Drivers and married clients had a high risk of being HIV+ (odds ratio [OR], 3.59; 95% confidence interval [CI], 2.17-5.96 and OR, 2.78; 95% CI, 2.42-3.19). Housewives were 2 times more likely to be positive (OR, 2.11; 95% CI, 1.35-3.29). After adjustment, females had 22% higher risk (OR, 1.22; 95% CI, 1.03-1.45) with the highest chance found in married females (OR, 6.70; 95% CI, 4.45-10.09). The study succeeded in panning out an unexpected risk group: married women. Drivers have been known to be a risk group. Preventive methods must be tailored to and acceptable by each risk group.