HIV subtype diversity worldwide.

PURPOSE OF REVIEW: To provide a summary of the current data on the global HIV subtype diversity and distribution by region. HIV is one of the most genetically diverse pathogens due to its high-mutation and recombination rates, large population size and rapid replication rate. This rapid evolutionary process has resulted in several HIV subtypes that are heterogeneously globally distributed. RECENT FINDINGS: Subtype A remains the most prevalent strain in parts of East Africa, Russia and former Soviet Union countries; subtype B in Europe, Americas and Oceania; subtype C in Southern Africa and India; CRF01_AE in Asia and CRF02_AG in Western Africa. Recent studies based on near full-length genome sequencing highlighted the growing importance of recombinant variants and subtype C viruses. SUMMARY: The dynamic change in HIV subtype distribution presents future challenges for diagnosis, treatment and vaccine design and development. An increase in recombinant viruses suggests that coinfection and superinfection by divergent HIV strains has become more common necessitating continuous surveillance to keep track of the viral diversity. Cheaper near full-length genome sequencing approaches are critical in improving HIV subtype estimations. However, missing subtype data and low sequence sampling levels are still a challenge in some geographical regions. VIDEO ABSTRACT: http://links.lww.com/COHA/A14

Prevention of the sexual transmission of HIV-1: preparing for success

There are four opportunities for HIV prevention: before exposure, at the moment of exposure, immediately after exposure, and as secondary prevention focused on infected subjects. Until recently, most resources have been directed toward behavioral strategies aimed at preventing exposure entirely. Recognizing that these strategies are not enough to contain the epidemic, investigators are turning their attention to post-exposure prevention opportunities. There is increasing focus on the use of ART–either systemic or topical (microbicides)–to prevent infection at the moment of exposure. Likewise, there is growing evidence that ART treatment of infected people could serve as prevention as well. A number of ongoing clinical trials will shed some light on the potential of these approaches. Above all, prevention of HIV requires decision-makers to focus resources on strategies that are most effective. Finally, treatment of HIV and prevention of HIV must be considered and deployed together

Short Communication: Choosing the Right Program for the Identification of HIV-1 Transmission Networks from Nucleotide Sequences Sampled from Different Populations.

HIV-TRAnsmission Cluster Engine (HIV-TRACE) and Cluster Picker are some of the most widely used programs for identifying HIV-1 transmission networks from nucleotide sequences. However, choosing between these tools is subjective and often a matter of personal preference. Because these software use different algorithms to detect HIV-1 transmission networks, their optimal use is better suited with different sequence data sets and under different scenarios. The performance of these tools has previously been evaluated across a range of genetic distance thresholds without an assessment of the differences in the structure of networks identified. In this study, we tested both programs on the same HIV-1 pol sequence data set (n?=?2,017) from three Ugandan populations to examine their performance across different risk groups and evaluate the structure of networks identified. HIV-TRACE that uses a single-linkage algorithm identified more nodes in the same networks that were connected by sparse links than Cluster Picker. This suggests that the choice of the program used for identifying networks should depend on the study aims, the characteristics of the population being investigated, dynamics of the epidemic, sampling design, and the nature of research questions being addressed for optimum results. HIV-TRACE could be more applicable with larger data sets where the aim is to identify larger clusters that represent distinct transmission chains and in more diverse populations where infection has occurred over a period of time. In contrast, Cluster Picker is applicable in situations where more closely connected clusters are expected in the studied populations

A prospective study of trends in consumption of cigarettes and alcohol among adults in a rural Ugandan population cohort, 1994-2011

OBJECTIVES: To characterise trends over time in smoking and alcohol consumption in a rural Ugandan population between 1994 and 2011. METHODS: We used self-reported data from a long-standing population cohort - the General Population Cohort. From 1989-1999, the study population comprised about 10,000 residents of 15 adjacent villages. From 1999, 10 more villages were added, doubling the population. Among adults (≥13 years, who comprise about half of the total study population) data on smoking were collected in 1994/95, 2008/9 and in 2010/11. Data on alcohol were collected in 1996/1997, 2000/2001, 2009/2010 and 2010/2011. RESULTS: The reported prevalence of smoking among men was 17% in 1994/1995, 14% in 2008/2009 and 16% in 2010/2011; equivalent figures for women were 1.5%, 1% and 2%. In the most recent time period, for both sexes combined, prevalence of smoking increased from 1.5% in those aged <29 years, to 18% in those 50+ years (P<0.001); prevalence was 14.8% in the lowest tertile of socio-economic status, decreasing to 3.7% in the highest (P<0.001). For alcohol consumption, current drinking was reported by 39% in 1996/1997, 35% in 2000/2001 and 28% in 2010/2011; men were more likely to drink than women (32.9% vs. 23.5% in 2010/2011) and consumption increased with age (P<0.001); was associated with low socio-economic status, riskier sexual behaviour and being HIV positive (P<0.001). CONCLUSION: In this rural Ugandan population, consumption of cigarettes and alcohol is higher among men than women, increases with age and is more frequent among those with low socio-economic status. We find no evidence of increases in either exposure over time. This article is protected by copyright. All rights reserved

'Test and Treat' Among Women at High Risk for HIV-infection in Kampala, Uganda: Antiretroviral Therapy Initiation and Associated Factors.

Data on implementation of 'Test and Treat' among key populations in sub-Saharan Africa are still limited. We examined factors associated with prompt antiretroviral therapy/ART (within 1 month of HIV-positive diagnosis or 1 week if pregnant) among 343 women at high risk for HIV infection in Kampala-Uganda, of whom 28% initiated prompt ART. Most (95%) reported paid sex within 3 months prior to enrolment. Multivariable logistic regression was used to determine baseline characteristics associated with prompt ART. Sex work as main job, younger age and being widowed/separated were associated with lower odds of prompt ART; being enrolled after 12 months of implementing the intervention was associated with higher odds of prompt ART. Younger women, widowed/separated and those reporting sex work as their main job need targeted interventions to start ART promptly after testing. Staff supervision and mentoring may need strengthening during the first year of implementing 'test and treat' interventions

Computational MHC-I epitope predictor identifies 95% of experimentally mapped HIV-1 clade A and D epitopes in a Ugandan cohort.

BACKGROUND: Identifying immunogens that induce HIV-1-specific immune responses is a lengthy process that can benefit from computational methods, which predict T-cell epitopes for various HLA types. METHODS: We tested the performance of the NetMHCpan4.0 computational neural network in re-identifying 93 T-cell epitopes that had been previously independently mapped using the whole proteome IFN-γ ELISPOT assays in 6 HLA class I typed Ugandan individuals infected with HIV-1 subtypes A1 and D. To provide a benchmark we compared the predictions for NetMHCpan4.0 to MHCflurry1.2.0 and NetCTL1.2. RESULTS: NetMHCpan4.0 performed best correctly predicting 88 of the 93 experimentally mapped epitopes for a set length of 9-mer and matched HLA class I alleles. Receiver Operator Characteristic (ROC) analysis gave an area under the curve (AUC) of 0.928. Setting NetMHCpan4.0 to predict 11-14mer length did not improve the prediction (37-79 of 93 peptides) with an inverse correlation between the number of predictions and length set. Late time point peptides were significantly stronger binders than early peptides (Wilcoxon signed rank test: p = 0.0000005). MHCflurry1.2.0 similarly predicted all but 2 of the peptides that NetMHCpan4.0 predicted and NetCTL1.2 predicted only 14 of the 93 experimental peptides. CONCLUSION: NetMHCpan4.0 class I epitope predictions covered 95% of the epitope responses identified in six HIV-1 infected individuals, and would have reduced the number of experimental confirmatory tests by > 80%. Algorithmic epitope prediction in conjunction with HLA allele frequency information can cost-effectively assist immunogen design through minimizing the experimental effort

Pregnancy, parturition and preeclampsia in women of African ancestry.

Maternal and associated neonatal mortality rates in sub-Saharan Africa remain unacceptably high. In Mulago Hospital (Kampala, Uganda), 2 major causes of maternal death are preeclampsia and obstructed labor and their complications, conditions occurring at the extremes of the birthweight spectrum, a situation encapsulated as the obstetric dilemma. We have questioned whether the prevalence of these disorders occurs more frequently in indigenous African women and those with African ancestry elsewhere in the world by reviewing available literature. We conclude that these women are at greater risk of preeclampsia than other racial groups. At least part of this susceptibility seems independent of socioeconomic status and likely is due to biological or genetic factors. Evidence for a genetic contribution to preeclampsia is discussed. We go on to propose that the obstetric dilemma in humans is responsible for this situation and discuss how parturition and birthweight are subject to stabilizing selection. Other data we present also suggest that there are particularly strong evolutionary selective pressures operating during pregnancy and delivery in Africans. There is much greater genetic diversity and less linkage disequilibrium in Africa, and the genes responsible for regulating birthweight and placentation may therefore be easier to define than in non-African cohorts. Inclusion of African women into research on preeclampsia is an essential component in tackling this major disparity of maternal health

Alternate primers for whole-genome SARS-CoV-2 sequencing.

As the world is struggling to control the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there is an urgency to develop effective control measures. Essential information is encoded in the virus genome sequence with accurate and complete SARS-CoV-2 sequences essential for tracking the movement and evolution of the virus and for guiding efforts to develop vaccines and antiviral drugs. While there is unprecedented SARS-CoV-2 sequencing efforts globally, approximately 19 to 43 per cent of the genomes generated monthly are gapped, reducing their information content. The current study documents the genome gap frequencies and their positions in the currently available data and provides an alternative primer set and a sequencing scheme to help improve the quality and coverage of the genomes

Virological failure on first-line antiretroviral therapy; associated factors and a pragmatic approach for switching to second line therapy-evidence from a prospective cohort study in rural South-Western Uganda, 2004-2011.

INTRODUCTION: We investigated factors affecting Virological failure (VF) on first line Antiretroviral Therapy (ART) and evaluated a pragmatic approach to switching to second line ART. METHODS: Between 2004 and 2011, we assessed adults taking ART. After 6 months or more on ART, participants with VL >1000 copies/ml or two successive VL > 400 copies/ml (Conventional VF) received intensified adherence counselling and continued on first-line ART for 6 more months, after which participants who still had VL > 1000 copies/ml (Pragmatic VF) were switched to second line ART. VF rates were calculated and predictors of failure were found by fitting logistic regression and Cox proportional hazards models. RESULTS: The 316 participants accrued 1036 person years at risk (pyar), 84 (26.6%) had conventional VF (rate 8.6 per 100 pyar) of whom 28 (33.3%) had pragmatic VF (rate 2.7 per 100 pyar). Independent predictors of conventional VF were; alcohol consumption, (adjusted Hazard Ratio; aHR = 1.71, 95% CI 1.05-2.79, P = 0.03) and ART adherence: per 10% decrease in proportion of adherent visits, (aHR = 1.83, 95% CI 1.50-2.23; P 40 years were 0.14, 95%CI 0.03-0.71, P = 0.02. Alcohol consumers had a threefold odds of pragmatic failure than non-alcohol consumers (aOR = 3.14, 95%CI 0.95-10.34, P = 0.06). CONCLUSION: A pragmatic VF approach is essential to guide switching to second line ART. Patient tailored ART adherence counselling among young patients and alcohol users is recommended

Comparison of HIV Risk Behaviors Between Clinical Trials and Observational Cohorts in Uganda.

Many key populations have high-risk behaviors for HIV infection making them suitable for HIV vaccine efficacy trials. However, these behaviors may change when participants enroll into a trial. We used HIV simulated vaccine efficacy trials (SiVETs) nested within observational cohorts of fisherfolks and female sex workers in Uganda to evaluate this difference. We screened observational cohort participants for enrolment into SiVETs, until 572 were enrolled. Those not enrolled (n = 953) continued participation in the observational cohorts. We determined risk behaviors at baseline and at 1 year, assigned a numeric score to each behavior and defined composite score as the sum of reported behaviors. We compared changes in scores over 12 months. Both observational cohorts and SiVETs saw a significant decrease in score but greatest in the SiVETs. Investigators recruiting for trials from these populations should consider the likely effect of reduction in risk behaviors on incident HIV infection and trial statistical power