Search

There is increasing evidence that HIV-1 viral protein R (Vpr) plays an important role in the pathogenesis of cognitive impairment. We investigated the relationship between HIV-1 sub-type C Vpr sequence variation and HIV-associated neurocognitive impairment as measured by global deficit score (GDS) in treatment naive individuals. We used different bioinformatic tools and statistical models to correlate vpr variation and cognitive function. We identified a Tyrosine at position 45 (45Y) as signature for neurocognitive impairment and Histidine (45H) as a signature in the non-impaired indviduals. The presence of signature 45Y was associated by 3.66 times higher GDS, 525 times higher plasma viral load, 15.84 times higher proviral load and 60% lower absolute CD4-T cell count compared those without the signature. Additionally, we identified 4 conserved Vpr fragment sequences, PEDQGPQREPYNEWTLE (5 to 21), LGQYIY(42 to 47), TYGDTW (49 to 54), PEDQGPQREPYNEW (5 to 18) that were associated with higher plasma viral load and proviral load. The implication of these findings is that variation of Vpr leads to neurocognitve impairment in HIV infection and worsens the progression of disease in general by promoting the production of provirus, promoting HIV replication and depletion of CD4+ T cells in the periphery. Key words: HAND, Vpr, entropy, signature amino acid residue, Tyrosine, Histidine.

Variation and differential selection pressures on Tat genes have been shown to alter the biological function of the protein, resulting in pathological consequences in a number of organs including the brain. We evaluated the impact of genetic variation and selection pressure on 147 HIV-1 subtype C Tat exon 1 sequences from monocyte-depleted peripheral lymphocytes on clinical diagnosis of neurocognitive impairment. Genetic analyses identified two signature amino acid residues, lysine at codon 24 (24K) with a frequency of 43.4% and arginine at codon 29 (29R) with a frequency of 34.0% in individuals with HIV-associated neurocognitive impairment. The analyses also revealed two signature residues, asparagine, 24 N (31.9%), and histidine, 29H (21.3%), in individuals without neurocognitive impairment. Both codons, 24 and 29, were associated with high entropy but only codon 29 was under positive selection. The presence of signature K24 increased by 2.08 times the risk of neurocognitive impairment, 3.15 times higher proviral load, and 69% lower absolute CD4 T-cell count compared to those without the signature. The results support a linkage between HIV-1 C Tat N24K polymorphism, proviral load, immunosuppression, and neurocognitive impairment. The signature may induce more neurotoxic effects, which contributes to establishment and severity of HIV-associated neurocognitive impairment.

Diagnosing HIV-associated neurocognitive impairment in most high-burden, but resource-constrained, settings is difficult due to the unavailability of specialist neurologists and neuropsychologists in primary health care centers. New tests that are easy to perform, based on virological and host immune response biomarkers, may be valuable in the diagnosis of HIV-associated neurocognitive disorder. The receiver operator characteristic curve analysis was used to investigate the diagnostic accuracy of threshold/cutoff concentrations for the peripheral lymphocyte proviral load and plasma biomarkers as diagnostic candidates for neurocognitive impairment in 133 HIV-infected individuals, using global deficit scores as the clinical gold standard. Forty-five (33.83%) of the participants had HIV-associated neurocognitive impairment, with 17.29% being mildly impaired and 16.54% moderately impaired. IL-2 had the best performance as a diagnostic tool for neurocognitive impairment with sensitivity of 67% and specificity of 52%, while the lowest performance was IL-6 with 65% sensitivity and 39% specificity. MIP-1α had the highest precision for the cutoff value, as indicated by the narrow 95% confidence interval (CI) (2.23-3.27), followed by IL-2 with 95% CI (3.02-5.12). RANTES had least precision, as shown by the widest 95% CI (135-9,487.61). For clinical markers of HIV diagnosis and monitoring, the lymphocyte proviral load cutoff value of 145 genome copies/million cells had the highest accuracy with 60% sensitivity and 51% specificity. The plasma viral load had an imperfect balance of 46% sensitivity and 78% specificity. The study demonstrated low to medium diagnostic accuracy of plasma cytokine biomarker cutoff values for defining neurocognitive impairment in people living with HIV.

Background: The SARS-CoV-2 Delta variant (B.1.617.2) has been associated with more severe disease, particularly when compared to the Alpha variant. Most of this data, however, is from high income countries and less is understood about the variant’s disease severity in other settings, particularly in an African context, and when compared to the Beta variant. Methods: A novel proxy marker, RNA-dependent RNA polymerase (RdRp) target delay in the Seegene AllplexTM 2019-nCoV (polymerase chain reaction) PCR assay, was used to identify suspected Delta variant infection in routine laboratory data. All cases diagnosed on this assay in the public sector in the Western Cape, South Africa, from 1 April to 31 July 2021, were included in the dataset provided by the Western Cape Provincial Health Data Centre (PHDC). The PHDC collates information on all COVID-19 related laboratory tests, hospital admissions and deaths for the province. Odds ratios for the association between the proxy marker and death were calculated, adjusted for prior diagnosed infection and vaccination status. Results: A total of 11,355 cases with 700 deaths were included in this study. RdRp target delay (suspected Delta variant) was associated with higher mortality (adjusted odds ratio [aOR] 1.45; 95% confidence interval [CI]: 1.13-1.86), compared to presumptive Beta infection. Prior diagnosed infection during the previous COVID-19 wave, which was driven by the Beta variant, was protective (aOR 0.32; 95%CI: 0.11-0.92) as was vaccination (aOR [95%CI] 0.15 [0.03-0.62] for complete vaccination [≥28 days post a single dose of Ad26.COV2.S or ≥14 days post second BNT162b2 dose]). Conclusion: RdRp target delay, a proxy for infection with the Delta variant, is associated with an increased risk of mortality amongst those who were tested for COVID-19 in our setting.

Central nervous system dysfunction, associated with human immunodeficiency virus (HIV) infection, remains a significant clinical concern, affecting at least 50% of infected people. Imbalances in cytokine expression levels have been linked to HIV-associated neurocognitive disorders. The aim of this study was to evaluate plasma cytokine levels as predictor neurocognitive impairment in HIV infection using a multiplex profiling kit. Stepwise regression model was used to identify cytokine biomarkers of overall and domain-specific cognitive performance. Higher interleukin (IL)-2 (

Continued uncontrolled transmission of SARS-CoV-2 in many parts of the world is creating conditions for substantial evolutionary changes to the virus1,2. Here we describe a newly arisen lineage of SARS-CoV-2 (designated 501Y.V2; also known as B.1.351 or 20H) that is defined by eight mutations in the spike protein, including three substitutions (K417N, E484K and N501Y) at residues in its receptor-binding domain that may have functional importance3,4,5. This lineage was identified in South Africa after the first wave of the epidemic in a severely affected metropolitan area (Nelson Mandela Bay) that is located on the coast of the Eastern Cape province. This lineage spread rapidly, and became dominant in Eastern Cape, Western Cape and KwaZulu–Natal provinces within weeks. Although the full import of the mutations is yet to be determined, the genomic data—which show rapid expansion and displacement of other lineages in several regions—suggest that this lineage is associated with a selection advantage that most plausibly results from increased transmissibility or immune escape6,7,8.

HIV-1 viral proteins have been implicated in endothelial dysfunction, which is a major determinant of ischaemic stroke risk in HIV-infected individuals. Polymorphisms in HIV-1 viral protein R (Vpr) may alter its potential to promote endothelial dysfunction, by modifying its effects on viral replication, reactivation of latent cells, upregulation of pro-inflammatory cytokines and infection of macrophages. We analysed Vpr polymorphisms and their association with acute ischaemic stroke by comparing Vpr signature amino acids between 54 HIV-infected individuals with acute ischaemic stroke, and 80 age-matched HIV-infected non-stroke controls. Isoleucine at position 22 and serine at position 41 were associated with ischaemic stroke in HIV. Individuals with stroke had lower CD4 counts and CD4 nadirs than controls. These polymorphisms are unique to individuals with stroke compared to South African subtype C and the control group consensus sequences. Signature Vpr polymorphisms are associated with acute ischaemic stroke in HIV. These may increase stroke risk by promoting endothelial dysfunction and susceptibility to opportunistic infections. Therapeutic targeting of HIV-1 viral proteins may present an additional mechanism of decreasing stroke risk in HIV-infected individuals.

The SARS-CoV-2 epidemic in southern Africa has been characterized by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, while the second and third waves were driven by the Beta (B.1.351) and Delta (B.1.617.2) variants, respectively1–3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron, B.1.1.529) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, which are predicted to influence antibody neutralization and spike function4. Here we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.

Objective Gene–environment interactions contribute to the development of HIV-associated neurocognitive disorders. We examined whether childhood trauma, apolipoprotein E isoforms and viral protein R (Vpr) variants were associated with change in cognitive performance. Seventy-three seropositive women completed neuropsychological assessments at baseline and 1-year follow-up. We conducted genetic analyses using DNA obtained from blood and calculated risk scores based on Vpr amino acid 37, 41 and 55 variants that were previously associated with cognitive performance. Results Global cognitive scores declined significantly over the 1-year study period (p = 0.029). A reduction in global cognitive scores was associated with childhood trauma experience (p = 0.039).

SummaryThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants respectively1–3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function4. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.

The progression of the SARS-CoV-2 pandemic in Africa has so far been heterogeneous and the full impact is not yet well understood. Here, 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 following 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 breeding ground for new variants.

HIV-1 proviral single-genome sequencing by limiting-dilution polymerase chain reaction (PCR) amplification is important for differentiating the sequence-intact from defective proviruses that persist during antiretroviral therapy (ART). Intact proviruses may rebound if ART is interrupted and are the barrier to an HIV cure. Oxford Nanopore Technologies (ONT) sequencing offers a promising, cost-effective approach to the sequencing of long amplicons such as near full-length HIV-1 proviruses, but the high diversity of HIV-1 and the ONT sequencing error render analysis of the generated data difficult. NanoHIV is a new tool that uses an iterative consensus generation approach to construct accurate, near full-length HIV-1 proviral single-genome sequences from ONT data. To validate the approach, single-genome sequences generated using NanoHIV consensus building were compared to Illumina® consensus building of the same nine single-genome near full-length amplicons and an average agreement of 99.4% was found between the two sequencing approaches.

Humanity is currently facing the challenge of two devastating pandemics caused by two very different RNA viruses: HIV-1, which has been with us for decades, and SARS-CoV-2, which has swept the world in the course of a single year. The same evolutionary strategies that drive HIV-1 evolution are at play in SARS-CoV-2. Single nucleotide mutations, multi-base insertions and deletions, recombination, and variation in surface glycans all generate the variability that, guided by natural selection, enables both HIV-1’s extraordinary diversity and SARS-CoV-2’s slower pace of mutation accumulation. Even though SARS-CoV-2 diversity is more limited, recently emergent SARS-CoV-2 variants carry Spike mutations that have important phenotypic consequences in terms of both antibody resistance and enhanced infectivity. We review and compare how these mutational patterns manifest in these two distinct viruses to provide the variability that fuels their evolution by natural selection. Fil: Fischer, Will. Los Alamos National Laboratory; Estados Unidos. New Mexico Consortium; México Fil: Giorgi, Elena E.. New Mexico Consortium; México. Los Alamos National Laboratory; Estados Unidos Fil: Chakraborty, Srirupa. Center For Nonlinear Studies; Estados Unidos. Los Alamos National Laboratory; Estados Unidos Fil: Nguyen, Kien. Los Alamos National Laboratory; Estados Unidos Fil: Bhattacharya, Tanmoy. Los Alamos National Laboratory; Estados Unidos Fil: Theiler, James. Los Alamos National Laboratory; Estados Unidos Fil: Goloboff, Pablo Augusto. American Museum of Natural History; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; Argentina Fil: Yoon, Hyejin. Los Alamos National Laboratory; Estados Unidos Fil: Abfalterer, Werner. Los Alamos National Laboratory; Estados Unidos Fil: Foley, Brian T.. Los Alamos National Laboratory; Estados Unidos Fil: Tegally, Houriiyah. University Of Kwazulu-natal; Sudáfrica Fil: San, James Emmanuel. University Of Kwazulu-natal; Sudáfrica Fil: de Oliveira, Tulio. University of KwaZulu-Natal; Sudáfrica Fil: Gnanakaran, Sandrasegaram. Los Alamos National Laboratory; Estados Unidos Fil: Korber, Bette. Los Alamos National Laboratory; Estados Unidos. New Mexico Consortium; México

The epidemic in South Africa is characterized by high genetic diversity driven by multiple independent introductions. The bulk of these introductions occurred between 1985–2000 during which time HIV prevalence increased exponentially. Epidemic growth has stabilized in recent years with the implementation of several interventions. Here we identified distinct HIV clades from a large sequence dataset of southern African HIV sequences (n = 15,332). Each clade was characterized using phylodynamic and phylogeographic methods to infer their growth through time and space. The estimated date of origin for the 18 clades that were found, fell between 1979–1992 with strong growth during the 1990’s. Phylogeographic reconstruction revealed wide dispersal of clades throughout the country with the city of Johannesburg as the focal point of viral dispersal. We found clear signs of decreasing growth rate in four of the clades since the advent of interventions, while other clades have continued to growth and expand. Our results demonstrate that interventions do not affect the HIV epidemic universally with major difference between different clades over time and space. Here we demonstrate the utility and flexibility of molecular epidemiological methods and demonstrate how they can potentially be a powerful tool in HIV epidemic monitoring in South Africa.

Background: HIV is accompanied by production of proinflammatory cytokines which are regarded as critical in neuronal damage, leading to brain dysfunction, hence the need to identify cytokine biomarkers sensitive to brain damage. Methods: We applied MRI volumetric neuroimaging and high throughput Luminex based immunoassays to examine the relationship between cortical white matter, subcortical gray matter and total gray matter brain volumes and plasma cytokines in HIV indviduals using generalised linear models and Partial least square regression model. Results: Higher plasma inflammatory cytokines CCL5/RANTES and MCP-1 were significantly associated with lower cortical white matter volume. Higher IL-6 was associated with both lower subcortical gray matter and lower total gray matter, whereas higher IL-8 and GM-CSF were associated with lower total gray matter only. Higher VEGF, PDGF-BB and IL-9 were associated with higher cortical white matter volumes. After standardisation and adjusting for clinical and demographic variables, IL-6, IL-8, MCP-1 remained associated with lower volumes of the three brain regions whereas IL-9, VEGF and PDGF-BB were associated with higher volumes. Conclusions: Association proinflammatory cytokines RANTES, MCP-1 and IL-6 with lower brain volumes could imply possible involvement in neurodegerative processes in HIV infection while IL-9, VEGF and PDGF may have a neuroprotective or neurotrophic role.

Cape Town was the first city in South Africa to experience the full impact of the coronavirus disease 2019 (COVID-19) pandemic. We acquired samples from all suspected cases and their contacts during the first month of the pandemic from Tygerberg Hospital. Nanopore sequencing generated SARS-CoV-2 whole genomes. Phylogenetic inference with maximum likelihood and Bayesian methods were used to determine lineages that seeded the local epidemic. Three patients were known to have travelled internationally and an outbreak was detected in a nearby supermarket. Sequencing of 50 samples produced 46 high-quality genomes. The sequences were classified as lineages: B, B.1, B.1.1.1, B.1.1.161, B.1.1.29, B.1.8, B.39, and B.40. All the sequences from persons under investigation (PUIs) in the supermarket outbreak (lineage B.1.8) fall within a clade from the Netherlands with good support (p > 0.9). In addition, a new mutation, 5209A>G, emerged within the Cape Town cluster. The molecular clock analysis suggests that this occurred around 13 March 2020 (95% confidence interval: 9–17 March). The phylogenetic reconstruction suggests at least nine early introductions of SARS-CoV-2 into Cape Town and an early localized transmission in a shopping environment. Genomic surveillance was successfully used to investigate and track the spread of early introductions of SARS-CoV-2 in Cape Town.

The first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in South Africa was identified on 5 March 2020, and by 26 March the country was in full lockdown (Oxford stringency index of 90)1. Despite the early response, by November 2020, over 785,000 people in South Africa were infected, which accounted for approximately 50% of all known African infections2. In this study, we analyzed 1,365 near whole genomes and report the identification of 16 new lineages of SARS-CoV-2 isolated between 6 March and 26 August 2020. Most of these lineages have unique mutations that have not been identified elsewhere. We also show that three lineages (B.1.1.54, B.1.1.56 and C.1) spread widely in South Africa during the first wave, comprising ~42% of all infections in the country at the time. The newly identified C lineage of SARS-CoV-2, C.1, which has 16 nucleotide mutations as compared with the original Wuhan sequence, including one amino acid change on the spike protein, D614G (ref. 3), was the most geographically widespread lineage in South Africa by the end of August 2020. An early South African-specific lineage, B.1.106, which was identified in April 2020 (ref. 4), became extinct after nosocomial outbreaks were controlled in KwaZulu-Natal Province. Our findings show that genomic surveillance can be implemented on a large scale in Africa to identify new lineages and inform measures to control the spread of SARS-CoV-2. Such genomic surveillance presented in this study has been shown to be crucial in the identification of the 501Y.V2 variant in South Africa in December 2020 (ref. 5).

Immune activation, which is accompanied by the production of proinflammatory cytokines, is a strong predictor of disease progression in HIV infection. Inflammation is critical in neuronal damage linked to HIV-associated neurocognitive disorders. We examined the relationship between plasma cytokine levels and deficits in neurocognitive function. Multiplex profiling by Luminex

SummaryContinued uncontrolled transmission of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in many parts of the world is creating the conditions for significant virus evolution. Here, we describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y) that may have functional significance. This lineage emerged in South Africa after the first epidemic wave in a severely affected metropolitan area, Nelson Mandela Bay, located on the coast of the Eastern Cape Province. This lineage spread rapidly, becoming within weeks the dominant lineage in the Eastern Cape and Western Cape Provinces. Whilst the full significance of the mutations is yet to be determined, the genomic data, showing the rapid displacement of other lineages, suggest that this lineage may be associated with increased transmissibility.

In March 2020, the first cases of COVID-19 were reported in South Africa. The epidemic spread very fast despite an early and extreme lockdown and infected over 600,000 people, by far the highest number of infections in an African country. To rapidly understand the spread of SARS-CoV-2 in South Africa, we formed the Network for Genomics Surveillance in South Africa (NGS-SA). Here, we analyze 1,365 high quality whole genomes and identify 16 new lineages of SARS-CoV-2. Most of these unique lineages have mutations that are found hardly anywhere else in the world. We also show that three lineages spread widely in South Africa and contributed to ∼42% of all of the infections in the country. This included the first identified C lineage of SARS-CoV-2, C.1, which has 16 mutations as compared with the original Wuhan sequence. C.1 was the most geographically widespread lineage in South Africa, causing infections in multiple provinces and in all of the eleven districts in KwaZulu-Natal (KZN), the most sampled province. Interestingly, the first South-African specific lineage, B.1.106, which was identified in April 2020, became extinct after nosocomial outbreaks were controlled. Our findings show that genomic surveillance can be implemented on a large scale in Africa to identify and control the spread of SARS-CoV-2.

It is not known if proviral DNA in the periphery corresponds to cognitive status in clade C as it does in clade B and recombinant forms. A cross-sectional study was conducted on participants investigated for HIV-associated neurocognitive impairment in South Africa. HIV-1 proviral DNA was quantified using a PCR assay targeting a highly conserved HIV-1 LTR-gag region. Fifty-four (36.7%) participants were cognitively impaired and 93 (63.3%) were not impaired. Forty-three (79.6%) of the cognitively impaired participants were female and 11 (20.4%) were male. There was no significant age difference between cognitively impaired and unimpaired participants (p = 0.42). HIV-1 DNA in cognitively impaired PLWH was significantly higher than in cognitively normal individuals (p = .016). Considering impaired participants, lymphocyte HIV-1 DNA was significantly higher in males than females (p = 0.02). There was a modest positive correlation between lymphocyte HIV-1 DNA and global deficit scores (GDS) r = 0.176; p = 0.03). The two measures of viral load, lymphocyte HIV-1 DNA copies/million and plasma RNA copies/ml, were positively correlated (r = 0.39; p p value = 0.010. The burden of HIV-1 peripheral blood lymphocyte proviral DNA corresponds to neurocognitive impairment among individuals infected with clade C disease. Therefore, therapeutic strategies to reduce the HIV-1 proviral DNA reservoir in lymphocytes may improve neurocognitive outcomes in PLWH.

In adults starting antiretroviral therapy (ART) during acute infection, 2% of proviruses that persist on ART are genetically intact by sequence analysis. In contrast, a recent report in children treated early failed to detect sequence-intact proviruses. In another cohort of children treated early, we sought to detect and characterize proviral sequences after 6 to 9 years on suppressive ART. Peripheral blood mononuclear cells (PBMC) from perinatally infected children from the Children with HIV Early antiRetroviral (CHER) study were analyzed. Nearly full-length proviral amplification and sequencing (NFL-PAS) were performed at one time point after 6 to 9 years on ART. Amplicons with large internal deletions were excluded (

Measuring contemporary dispersal in highly mobile terrestrial species is challenging, especially when species are characterized by low levels of population differentiation. Directly transmitted viruses can be used as a surrogate for traditional methods of tracking host movement. Feline immunodeficiency virus (FIV) is a species-specific lentivirus, which has an exceptionally high mutation rate and circulates naturally in wild felids. Using samples derived from 35 lion (Panthera leo) prides, we tested the prediction that FIV in lions (FIVP le ) can be used to track the dispersal of individuals between prides. As FIVP le subtypes are geographically structured throughout Africa, we predicted that this marker could be used to detect phylogeographic structure of lions at smaller spatial scales. Phylogenetic analyses of FIVP le pol-RT sequences showed that core pride members (females and subadults) shared evolutionary close viral lineages which differed from neighbouring core prides, whereas sequences from sexually mature males associated with the same pride were always the most divergent. In six instances, natal pride associations of divergent male lions could be inferred, on the assumption that FIVP le infections are acquired during early life stages. Congruence between the genetic pattern of FIV and pride structure suggests that vertical transmission plays an important role in lion FIV dynamics. At a fine spatial scale, significant viral geographic structuring was also detected between lions occurring north of the Olifants River within the Kruger National Park (KNP) and those occupying the southern and central regions. This pattern was further supported by phylogenetic analyses and the confinement of FIVP le subtype E to the northern region of KNP. The study provides new insights into the use of retroviral sequences to predict host dispersal and fine-scale contemporary geographic structure in a social felid species.

To obtain more insights into the prevalence and diversity of species-specific Feline Immunodeficiency Virus (FIV) strains in naturally occurring felid species, 26 leopards (Panthera pardus) from the Kruger National Park (KNP), South Africa, were sampled. Prevalence was determined using a PCR protocol designed to target a 577 bp fragment in the pol-RT gene. Overall prevalence of FIVPpa was estimated at 73%, with no difference in prevalence between male and female leopards. Consistent with previous FIV studies on other felid species, prevalence appears to increase with age (adult = 84%; subadult = 43%). Phylogenetic analyses of these novel sequences were conducted against a revised FIV pol-RT species-specific reference dataset using both Bayesian and maximum likelihood methods. Within FIVPpa two distinct evolutionary groupings are present, which suggests the possibility of geographic variation within FIVPpa and the possibility of distinct subtypes, similar to what has been found in lions (Panthera leo) and domestic cats (Felis catus). The larger FIVPpa dataset provides newinsights into the epidemiology of this under-studied FIV strain and with such high prevalence rates, further studies should focus on immunological and clinical consequences of FIV in wild felids.

Background: HPV antibodies are a marker of past exposure to the virus. Our objective was to assess HPV serostatus pre- and post-vaccination among HIV-negative women. Methods: Women aged 16â24 years old were randomized in a placebo controlled trial utilizing the 4-valent HPV (4vHPV) vaccine (NCT01489527, clinicaltrials.gov). Participants (n=389) received the 4vHPV vaccine or placebo following a three dose schedule. Sera were collected at Day 1 and Month 7 for assessment of HPV 6, 11, 16, and 18 neutralizing antibody levels using a multiplex competitive Luminex immunoassay (Merck) based on detecting the L1 capsid antigen for each HPV type. Results: Seroprevalence was 73% for HPV6, 47% for HPV11, 33% for HPV16, and 44% for HPV18. Seroprevalence for any HPV type did not significantly differ by age or lifetime number of partners. The majority of participants (64%) had two or more 4vHPV antibodies present at enrollment and 12% had antibodies to all four. Among women in the vaccine arm, those that were seropositive for HPV16 at enrollment had higher titers at month 7 compared to women that were seronegative for HPV16 at enrollment; this trend holds for the other HPV types as well. Seroconversion among baseline seronegative participants in the placebo group ranged from 5% for HPV16 to 23% for HPV6. Conclusion: HPV seroprevalence was high in this population, emphasizing the need to vaccinate prior to sexual debut. Keywords: HPV vaccine, EVRI, Seroprevalence, cLIA

ObjectiveTo estimate the prevalence and describe the patterns of concurrent human papillomavirus (HPV) and STIs and associated factors among HIV-negative young Western Cape, South African women participating in the Efficacy of HPV Vaccine to Reduce HIV Infection (EVRI) trial.MethodsHIV-negative women aged 16–24 years old were enrolled in the EVRI trial (NCT01489527) and randomised to receive the licensed four-valent HPV vaccine or placebo. At study entry, participants were clinically evaluated for five STIs: herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis and disease-causing HPV genotypes (6/11/16/18/31/33/35/39/45/51/52/56/58/59/68). Demographic and sexual history characteristics were compared among women with STI co-infections, single infection and no infection using Pearson χ2and Mann-Whitney tests. ORs were calculated to evaluate factors associated with STI co-infection prevalence.ResultsAmong 388 young women, STI co-infection prevalence was high: 47% had ≥2 concurrent STIs, 36% had a single STI and 17% had none of the five evaluated STIs. HPV/HSV-2 (26%) was the most prevalent co-infection detected followed by HPV/HSV-2/Chlamydia trachomatis(CT) (17%) and HPV/CT (15%). Co-infection prevalence was independently associated with alcohol use (adjusted OR=2.01, 95% CI 1.00 to 4.06) and having a sexual partner with an STI (adjusted OR=6.96, 95% CI 1.53 to 30.08).ConclusionsAmong high-risk young women from underserved communities such as in Southern Africa, a multicomponent prevention strategy that integrates medical and behavioural interventions targeting both men and women is essential to prevent acquisition of concurrent STI infections and consequent disease.Trial registration numberNCT01489527; Post-results.

Background While the HIV epidemic in South Africa had a later onset than epidemics in other southern African countries, prevalence grew rapidly during the 1990′s when the country was going through socio-political changes with the end of Apartheid. South Africa currently has the largest number of people living with HIV in the world and the epidemic is dominated by a unique subtype, HIV-1 subtype C. This large epidemic is also characterized by high level of genetic diversity. We hypothesize that this diversity is due to multiple introductions of the virus during the period of change. In this paper, we apply novel phylogeographic methods to estimate the number of viral imports and exports from the start of the epidemic to the present. Methods We assembled 11,289 unique subtype C pol sequences from southern Africa. These represent one of the largest sequence datasets ever analyzed in the region. Sequences were stratified based on country of sampling and levels of genetic diversity were estimated for each country. Sequences were aligned and a maximum-likelihood evolutionary tree was inferred. Least-Squares Dating was then used to obtain a dated phylogeny from which we estimated the number of introductions into and exports out of South Africa using parsimony-based ancestral location reconstructions. Results Our results identified 189 viral introductions into South Africa with the largest number of introductions attributed to Zambia (n = 109), Botswana (n = 32), Malawi (n = 26) and Zimbabwe (n = 13). South Africa also exported many viral lineages to its neighbours. The bulk viral imports and exports appear to have occurred between 1985 and 2000, coincident with the period of socio-political transition. Conclusion The high level of subtype C genetic diversity in South Africa is related to multiple introductions of the virus to the country. While the number of viral imports and exports we identified was highly sensitive to the number of samples included from each country, they mostly clustered around the period of rapid political and socio-economic change in South Africa.

HIV-1 subtype C is the most prevalent subtype in South Africa. Although subtype B was previously detected in South Africa, there is limited sequence information available. We characterized near full-length HIV-1 subtype B sequences from samples collected at the start of the South African HIV-1 epidemic, in the 1980s. Five samples were analysed by PCR amplification, Sanger DNA sequencing and phylogenetic analyses. The viral genomes were amplified in two overlapping fragments of 5.5 kb and 3.7 kb. The sequences were subtyped using REGA version 3.0, RIP version 3.0 and jpHMM. Maximum Likelihood phylogenetic trees were inferred with MEGA version 6. Four HIV-1 patient sequences were subtyped as pure HIV-1 subtype B. One sequence was characterized as a novel HIV-1 subtype B and D recombinant. The sequences clustered phylogenetically with other HIV-1 subtype B sequences from South Africa, Europe and the USA. We report the presence of an HIV-1 subtype B and D recombinant strain detected in the beginning of the epidemic. This indicates that viral recombination events were already happening in 1985, but could have been missed as sequence analyses were often limited to small genomic regions of HIV-1.

Background: In adults starting ART during acute infection, 2% of proviruses that persist on ART are intact (replication-competent) by sequence analysis. By contrast, a recent report in early treated children failed to detect sequence intact proviruses. We sought to detect and characterize proviral sequences in another cohort of early treated children after 6-9 years on suppressive ART. Methods: PBMCs from perinatally-infected children from the CHER study were analysed. Near full-length proviral amplification and sequencing (NFL-PAS) was performed at one time point after 6-9 years on ART. Amplicons with large internal deletions were excluded (

Summary Objective The objective of this analysis was to assess human papillomavirus (HPV) infection persistence and incidence 7-months post-enrollment by HPV vaccine study arm (vaccine or placebo). Methods HIV-negative, sexually active women aged 16–24 years in the Western Cape, South Africa, were enrolled in the EVRI Trial and were randomized to receive 4-valent HPV vaccine or placebo. Cervical specimens were collected at enrollment and at the 7-month visit and were genotyped for HPV. HPV prevalence, persistence, and incidence were calculated. Prevalence ratios and odds ratios were calculated to assess factors associated with a prevalent and incident HPV infection. Results HPV incidence rates were marginally higher for the placebo group (n = 163) compared to the vaccine group (n = 169). A large proportion of the prevalent high-risk (HR-HPV) HPV types (49%) persisted over the 7-month period in both arms. Prevalent HR-HPV infection was significantly associated with a prevalent gonorrhea infection and detection of Herpes simplex type 2 antibodies. Incident HR-HPV infection was significantly associated with abnormal cervical cytology at enrollment and younger age. Conclusions Women living in geographic areas, such as southern Africa, at high-risk for HPV need to receive HPV vaccination at a very young age to maximally prevent infection and subsequent disease.

This study examines white matter microstructure using quantitative tractography diffusion magnetic resonance imaging (qtdMRI) in HIV+ individuals from South Africa who were naive or early in the initiation of antiretroviral therapy. Fiber bundle length (FBL) metrics, generated from qtdMRI, for whole brain and six white matter tracts of interest (TOI) were assessed for 135 HIV+ and 21 HIV− individuals. The association between FBL metrics, measures of disease burden, and neuropsychological performance were also investigated. Results indicate significantly reduced sum of whole brain fiber bundle lengths (FBL, p

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

HIV-Integrase (IN) has proven to be a viable target for highly specific HIV-1 therapy. We aimed to characterize the HIV-1 IN gene in a South African context and identify resistance-associated mutations (RAMs) against available first and second generation Integrase strand-transfer inhibitors (InSTIs). We performed genetic analyses on 91 treatment-naïve HIV-1 infected patients, as well as 314 treatment-naive South African HIV-1 IN-sequences, downloaded from Los Alamos HIV Sequence Database. Genotypic analyses revealed the absence of major RAMs in the cohort collected before the broad availability of combination antiretroviral therapy (cART) and INSTI in South Africa, however, occurred at a rate of 2.85% (9/314) in database derived sequences. RAMs were present at IN-positions 66, 92, 143, 147 and 148, all of which may confer resistance to Raltegravir (RAL) and Elvitegravir (EVG), but are unlikely to affect second-generation Dolutegravir (DTG), except mutations in the Q148 pathway. Furthermore, protein modeling showed, naturally occurring polymorphisms impact the stability of the intasome-complex and therefore may contribute to an overall potency against InSTIs. Our data suggest the prevalence of InSTI RAMs, against InSTIs, is low in South Africa, but natural polymorphisms and subtype-specific differences may influence the effect of individual treatment regimens.