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.K.E.B. is supported by Wellcome Trust award number 170461. N.N. is supported by NIH R01 AI147331-01. R.K.G. is supported by a Wellcome Trust Senior Fellowship in Clinical Science (WT108082AIA). This study was supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of U2G GH002099-01 and PA GH17-1753 (ACHIEVE)

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

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. 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. 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. 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.https://doi.org/10.1186/s12889-021-11275-

Patient Retention and Adherence to Antiretrovirals in a Large Antiretroviral Therapy Program in Nigeria: A Longitudinal Analysis for Risk Factors

Substantial resources and patient commitment are required to successfully scale-up antiretroviral therapy (ART) and provide appropriate HIV management in resource-limited settings. We used pharmacy refill records to evaluate risk factors for loss to follow-up (LTFU) and non-adherence to ART in a large treatment cohort in Nigeria.We reviewed clinic records of adult patients initiating ART between March 2005 and July 2006 at five health facilities. Patients were classified as LTFU if they did not return >60 days from their expected visit. Pharmacy refill rates were calculated and used to assess non-adherence. We identified risk factors associated with LTFU and non-adherence using Cox and Generalized Estimating Equation (GEE) regressions, respectively. Of 5,760 patients initiating ART, 26% were LTFU. Female gender (p < 0.001), post-secondary education (p = 0.03), and initiating treatment with zidovudine-containing (p = 0.004) or tenofovir-containing (p = 0.05) regimens were associated with decreased risk of LTFU, while patients with only primary education (p = 0.02) and those with baseline CD4 counts (cell/ml(3)) >350 and <100 were at a higher risk of LTFU compared to patients with baseline CD4 counts of 100-200. The adjusted GEE analysis showed that patients aged <35 years (p = 0.005), who traveled for >2 hours to the clinic (p = 0.03), had total ART duration of >6 months (p<0.001), and CD4 counts >200 at ART initiation were at a higher risk of non-adherence. Patients who disclosed their HIV status to spouse/family (p = 0.01) and were treated with tenofovir-containing regimens (p < or = 0.001) were more likely to be adherent.These findings formed the basis for implementing multiple pre-treatment visit preparation that promote disclosure and active community outreaching to support retention and adherence. Expansion of treatment access points of care to communities to diminish travel time may have a positive impact on adherence

Tumorigenesis by Human Herpesvirus 8 vGPCR Is Accelerated by Human Immuodeficiency Virus Type 1 Tat

Human herpesvirus 8 (HHV-8), also called Kaposi's sarcoma (KS) herpesvirus, can cause KS but is inefficient. Untreated human immunodeficiency virus type 1 (HIV-1) coinfection is a powerful risk factor. The HHV-8 chemokine receptor, vGPCR (ORF74), activates NF-κB and NF-AT, and their levels of activation are synergistically increased by HIV-1 Tat. Transgenic vGPCR mice develop KS-like tumors. A cell line derived from one such tumor expresses vGPCR and forms tumors in nude mice. Here we show that transfection of DNA encoding HIV-1 tat (but not a transactivation-defective mutant) into these tumor cells increases NF-κB and NF-AT activation levels and accelerates tumor formation. Tumorigenesis was also accelerated when Tat DNA was transfected into normal cells and the transfected cells were mixed with the tumor cells and injected into a single site. Tumorigenesis was also increased when the two cell types were injected at separate sites, suggesting that tumorigenesis is accelerated by Tat through soluble factors

Characterisation of HIV-1 Molecular Epidemiology in Nigeria : Origin, Diversity, Demography and Geographic Spread

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

Key Population Size Estimation to Guide HIV Epidemic Responses in Nigeria: Bayesian Analysis of 3-Source Capture-Recapture Data

BackgroundNigeria has the fourth largest burden of HIV globally. Key populations, including female sex workers, men who have sex with men, and people who inject drugs, are more vulnerable to HIV than the general population due to stigmatized and criminalized behaviors. Reliable key population size estimates are needed to guide HIV epidemic response efforts. ObjectiveThe objective of our study was to use empirical methods for sampling and analysis to improve the quality of population size estimates of female sex workers, men who have sex with men, and people who inject drugs in 7 states (Akwa Ibom, Benue, Cross River, Lagos, Nasarawa, Rivers, and the Federal Capital Territory) of Nigeria for program planning and to demonstrate improved statistical estimation methods. MethodsFrom October to December 2018, we used 3-source capture-recapture to produce population size estimates in 7 states in Nigeria. Hotspots were mapped before 3-source capture-recapture started. We sampled female sex workers, men who have sex with men, and people who inject drugs during 3 independent captures about one week apart. During hotspot encounters, key population members were offered inexpensive, memorable objects unique to each capture round. In subsequent rounds, key population members were offered an object and asked to identify objects received during previous rounds (if any). Correct responses were tallied and recorded on tablets. Data were aggregated by key population and state for analysis. Median population size estimates were derived using Bayesian nonparametric latent-class models with 80% highest density intervals. ResultsOverall, we sampled approximately 310,000 persons at 9015 hotspots during 3 independent captures. Population size estimates for female sex workers ranged from 14,500 to 64,300; population size estimates for men who have sex with men ranged from 3200 to 41,400; and population size estimates for people who inject drugs ranged from 3400 to 30,400. ConclusionsThis was the first implementation of these 3-source capture-recapture methods in Nigeria. Our population size estimates were larger than previously documented for each key population in all states. The Bayesian models account for factors, such as social visibility, that influence heterogeneous capture probabilities, resulting in more reliable population size estimates. The larger population size estimates suggest a need for programmatic scale-up to reach these populations, which are at highest risk for HIV

Revealing human mobility trends during the SARS-CoV-2 pandemic in Nigeria via a data-driven approach

We employed emerging smartphone-based location data and produced daily human mobility measurements using Nigeria as an application site. A data-driven analytical framework was developed for rigorously producing such measures using proven location intelligence and data-mining algorithms. Our study demonstrates the framework at the beginning of the SARS-CoV-2 pandemic and successfully quantifies human mobility patterns and trends in response to the unprecedented public health event. Another highlight of the paper is the assessment of the effectiveness of mobility-restricting policies as key lessons learned from the pandemic. We found that travel bans and federal lockdown policies failed to restrict trip-making behaviour, but had a significant impact on distance travelled. This paper contributes a first attempt to quantify daily human travel behaviour, such as trip-making behaviour and travelling distances, and how mobility-restricting policies took effect in sub-Saharan Africa during the pandemic. This study has the potential to enable a wide spectrum of quantitative studies on human mobility and health in sub-Saharan Africa using well-controlled, publicly available large data sets. Significance: The mobility measurements in this study are new and have filled a major data gap in understanding the change in travel behaviour during the SARS-CoV-2 pandemic in Nigeria. These measurements are derived from high-quality data samples by state-of-the-art data-driven methodologies and could be further adopted by other quantitative research related to human mobility. Additionally, this study evaluates the impact of mobility-restricting policies and the heterogeneous effects of socio-economic and socio-demographic factors by a time-dependent random effect model on human mobility. The quantitative model provides a decision-making basis for the Nigerian government to provide travel-related guidance and make decisions in future public health events. Open data set: https://github.com/villanova-transportation/Nigeria-mobility-COVID19-SAJ

Cocaine Use May Moderate the Associations of HIV and Female Sex with Neurocognitive Impairment in a Predominantly African American Population Disproportionately Impacted by HIV and Substance Use

HIV-associated neurocognitive disorders (HAND) remain a major challenge for people with HIV in the antiretroviral therapy era. Cocaine use may trigger/exacerbate HAND among African American (AA) adults, especially women. Between 2018 and 2019, 922 adults, predominantly AAs, with/without HIV and with/without cocaine use in Baltimore, Maryland, were enrolled in a study investigating the association of HIV and cocaine use with neurocognitive impairment (NCI). Neurocognitive performance was assessed with the NIH Toolbox Cognition Battery (NIHTB-CB). NCI was considered to be present if the fully adjusted standard score for at least two cognitive domains was 1.0 standard deviation below the mean. Although the overall analysis showed HIV and female sex were associated with NCI, the associations were dependent on cocaine use. Neither HIV [adj prevalence ratio (PR): 1.12, confidence interval (95% CI): 0.77-1.64] nor female sex (adj PR: 1.07, 95% CI: 0.71-1.61) was associated with NCI among cocaine nonusers, while both HIV (adj PR: 1.39, 95% CI: 1.06-1.81) and female sex (adj PR: 1.53, 95% CI: 1.18-1.98) were associated with NCI in cocaine users. HIV was associated with two NIHTB-CB measures overall. In addition, HIV was associated with a lower dimensional change card sort score (an executive function measure) in cocaine users and not in nonusers. Cognitive performance was poorer in female than in male cocaine users. The adverse effect of HIV on cognitive performance predominantly affected cocaine users. However, cocaine use may moderate the impact of HIV and female sex on cognitive performance, highlighting the importance of reducing cocaine use in NCI prevention among the AA population