Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in Nigeria

Background: To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1st- and 2nd-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3rd-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations. Methods and Findings: From 2004–2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for 24 months. Patients developed a median of 0.6 (IQR: 0–1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir. Conclusions: This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access

Technology in Massachusetts Schools, 2004-2005

BACKGROUND:ATCC HIV-1 drug resistance test kit was designed to detect HIV-1 drug resistance (HIVDR) mutations in the protease and reverse transcriptase genes for all HIV-1 group M subtypes and circulating recombinant forms. The test has been validated for both plasma and dried blood spot specimen types with viral load (VL) of ≥1000 copies/ml. We performed an in-country assessment on the kit to determine the genotyping sensitivity and its accuracy in detecting HIVDR mutations using plasma samples stored under suboptimal conditions. METHODS:Among 572 samples with VL ≥1000 copies/ml that had been genotyped by ViroSeq assay, 183 were randomly selected, including 85 successful genotyped and 98 unsuccessful genotyped samples. They were tested with ATCC kits following the manufacturer's instructions. Sequence identity and HIVDR patterns were analysed with Stanford University HIV Drug Resistance HIVdb program. RESULTS:Of the 183 samples, 127 (69.4%) were successfully genotyped by either method. While ViroSeq system genotyped 85/183 (46.5%) with median VL of 32,971 (IQR: 11,150-96,506) copies/ml, ATCC genotyped 115/183 (62.8%) samples with median VL of 23,068 (IQR: 7,397-86,086) copies/ml. Of the 98 unsuccessful genotyped samples with ViroSeq assay, 42 (42.9%) samples with lower median VL of 13,906 (IQR: 6,122-72,329) copies/ml were successfully genotyped using ATCC. Sequence identity analysis revealed that the sequences generated by both methods were >98% identical and yielded similar HIVDR profiles at individual patient level. CONCLUSION:This study confirms that ATCC kit showed greater sensitivity in genotyping plasma samples stored in suboptimal conditions experiencing frequent and prolonged power outage. Thus, it is more sensitive particularly for subtypes A and A/G HIV-1 in resource-limited settings

Multidisciplinary approach to genomics research in Africa:the AfriCRAN model

This article is an outcome of the African Craniofacial Anomalies Research Network (AfriCRAN) Human Hereditary and Health (H3A) grant planning meeting in 2012 in Lagos, Nigeria. It describes the strengths of a multidisciplinary team approach to solving complex genetic traits in the craniofacial region. It also highlights the different components and argues for the composition of similar teams to fast track the discovery of disease genes, diagnostic tools, improved clinical treatment and ultimately prevention of disease

SARS-CoV-2 sequencing collaboration in west Africa shows best practices.

Correspondence - No abstract available

Novel <i>GREM1 </i>Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate

Objective: Cleft lip and/or cleft palate (CL/P) are congenital anomalies of the face and have multifactorial etiology, with both environmental and genetic risk factors playing crucial roles. Though at least 40 loci have attained genomewide significant association with nonsyndromic CL/P, these loci largely reside in noncoding regions of the human genome, and subsequent resequencing studies of neighboring candidate genes have revealed only a limited number of etiologic coding variants. The present study was conducted to identify etiologic coding variants in GREM1, a locus that has been shown to be largely associated with cleft of both lip and soft palate. Patients and Method: We resequenced DNA from 397 sub-Saharan Africans with CL/P and 192 controls using Sanger sequencing. Following analyses of the sequence data, we observed 2 novel coding variants in GREM1. These variants were not found in the 192 African controls and have never been previously reported in any public genetic variant database that includes more than 5000 combined African and African American controls or from the CL/P literature. Results: The novel variants include p.Pro164Ser in an individual with soft palate cleft only and p.Gly61Asp in an individual with bilateral cleft lip and palate. The proband with the p.Gly61Asp GREM1 variant is a van der Woude (VWS) case who also has an etiologic variant in IRF6 gene. Conclusion: Our study demonstrated that there is low number of etiologic coding variants in GREM1, confirming earlier suggestions that variants in regulatory elements may largely account for the association between this locus and CL/P. </jats:sec

Prevalence and risk factors for high-risk human papillomavirus infection among women from three southern geopolitical zones of Nigeria

IntroductionHuman Papillomavirus (HPV) infection is a risk factor for cervical cancer, the fourth most common cancer among women globally. Its burden is the highest in sub-Saharan Africa, with over 90% mortality. Interventions may fail without evidence-based data on stratified prevalence and risk factors among most at-risk women across Nigeria.MethodsA cross-sectional comparative study, with participants recruited from the Nigerian Institute of Medical Research’s Clinics, NGO outreaches, a cancer screening centre and a university teaching hospital. Questionnaires were self-administered. Trained medics performed sampling at healthcare facilities, and self-sampling was used at outreaches.ResultsNine hundred eighty-five study participants were recruited. About 37% and 27% of the women knew about HPV and its vaccines, respectively, but only 6% confirmed vaccination with HPV vaccines. HPV prevalence was highest among women with unknown marital status (35.9%), single women (33.8%), widowed/divorced/separated women (30.3%), and married/cohabiting women (19.6%). HPV infection was significantly higher among women who take alcohol (odds=1.7 [95% CI: 1.2-2.4]) and women who smoke (odds=2.6 [95% CI: 1.4 - 4.6]. HPV strains detected included HPV16 (1.3%), HPV18 (1.5%), Low Risk (0.2%) and Other High-Risk groups (19.7%).ConclusionThe inverse relationship between prevalence and education suggests interventions improving awareness and prevention would be impactful. Such interventions could also target HIV-positive women, women presenting with sexually-transmitted infections, who smoke and frequently drink alcohol

Emergence and spread of two SARS-CoV-2 variants of interest in Nigeria.

Identifying the dissemination patterns and impacts of a virus of economic or health importance during a pandemic is crucial, as it informs the public on policies for containment in order to reduce the spread of the virus. In this study, we integrated genomic and travel data to investigate the emergence and spread of the SARS-CoV-2 B.1.1.318 and B.1.525 (Eta) variants of interest in Nigeria and the wider Africa region. By integrating travel data and phylogeographic reconstructions, we find that these two variants that arose during the second wave in Nigeria emerged from within Africa, with the B.1.525 from Nigeria, and then spread to other parts of the world. Data from this study show how regional connectivity of Nigeria drove the spread of these variants of interest to surrounding countries and those connected by air-traffic. Our findings demonstrate the power of genomic analysis when combined with mobility and epidemiological data to identify the drivers of transmission, as bidirectional transmission within and between African nations are grossly underestimated as seen in our import risk index estimates

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa.

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants