Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS.

HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors - synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.

Decreased severity of disease during the first global omicron variant covid-19 outbreak in a large hospital in tshwane, south africa.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) first reported in Wuhan, China in December 2019 is a global pandemic that is threatening the health and wellbeing of people worldwide. To date there have been more than 274 million reported cases and 5.3 million deaths. The Omicron variant first documented in the City of Tshwane, Gauteng Province, South Africa on 9 November 2021 led to exponential increases in cases and a sharp rise in hospital admissions. The clinical profile of patients admitted at a large hospital in Tshwane is compared with previous waves. METHODS: 466 hospital COVID-19 admissions since 14 November 2021 were compared to 3962 admissions since 4 May 2020, prior to the Omicron outbreak. Ninety-eight patient records at peak bed occupancy during the outbreak were reviewed for primary indication for admission, clinical severity, oxygen supplementation level, vaccination and prior COVID-19 infection. Provincial and city-wide daily cases and reported deaths, hospital admissions and excess deaths data were sourced from the National Institute for Communicable Diseases, the National Department of Health and the South African Medical Research Council. RESULTS: For the Omicron and previous waves, deaths and ICU admissions were 4.5% vs 21.3% (p<0.00001), and 1% vs 4.3% (p<0.00001) respectively; length of stay was 4.0 days vs 8.8 days; and mean age was 39 years vs 49,8 years. Admissions in the Omicron wave peaked and declined rapidly with peak bed occupancy at 51% of the highest previous peak during the Delta wave. Sixty two (63%) patients in COVID-19 wards had incidental COVID-19 following a positive SARS-CoV-2 PCR test . Only one third (36) had COVID-19 pneumonia, of which 72% had mild to moderate disease. The remaining 28% required high care or ICU admission. Fewer than half (45%) of patients in COVID-19 wards required oxygen supplementation compared to 99.5% in the first wave. The death rate in the face of an exponential increase in cases during the Omicron wave at the city and provincial levels shows a decoupling of cases and deaths compared to previous waves, corroborating the clinical findings of decreased severity of disease seen in patients admitted to the Steve Biko Academic Hospital. CONCLUSION: There was decreased severity of COVID-19 disease in the Omicron-driven fourth wave in the City of Tshwane, its first global epicentre.

Comorbidity in context: Part 2. Ethicolegal considerations around HIV and tuberculosis during the COVID-19 pandemic in South Africa.

The COVID-19 pandemic has brought discussions around the appropriate and fair rationing of scare resources to the forefront. This is of special importance in a country such as South Africa (SA), where scarce resources interface with high levels of need. A large proportion of the SA population has risk factors associated with worse COVID-19 outcomes. Many people are also potentially medically and socially vulnerable secondary to the high levels of infection with HIV and tuberculosis (TB) in the country. This is the second of two articles. The first examined the clinical evidence regarding the inclusion of HIV and TB as comorbidities relevant to intensive care unit (ICU) admission triage criteria. Given the fact that patients with HIV or TB may potentially be excluded from admission to an ICU on the basis of an assumption of lack of clinical suitability for critical care, in this article we explore the ethicolegal implications of limiting ICU access of persons living with HIV or TB. We argue that all allocation and rationing decisions must be in terms of SA law, which prohibits unfair discrimination. In addition, ethical decision-making demands accurate and evidence-based strategies for the fair distribution of limited resources. Rationing decisions and processes should be fair and based on visible and consistent criteria that can be subjected to objective scrutiny, with the ultimate aim of ensuring accountability, equity and fairness.

Comorbidity in context: Part 1. Medical considerations around HIV and tuberculosis during the COVID-19 pandemic in South Africa.

Infectious diseases pandemics have devastating health, social and economic consequences, especially in developing countries such as South Africa. Scarce medical resources must often be rationed effectively to contain the disease outbreak. In the case of COVID-19, even the best-resourced countries will have inadequate intensive care facilities for the large number of patients needing admission and ventilation. The scarcity of medical resources creates the need for national governments to establish admission criteria that are evidence-based and fair. Questions have been raised whether infection with HIV or tuberculosis (TB) may amplify the risk of adverse COVID-19 outcomes and therefore whether these conditions should be factored in when deciding on the rationing of intensive care facilities. In light of these questions, clinical evidence regarding inclusion of these infections as comorbidities relevant to intensive care unit admission triage criteria is investigated in the first of a two-part series of articles. There is currently no evidence to indicate that HIV or TB infection on their own predispose to an increased risk of infection with SARS-CoV-2 or worse outcomes for COVID-19. It is recommended that, as for other medical conditions, validated scoring systems for poor prognostic factors should be applied. A subsequent article examines the ethicolegal implications of limiting intensive care access of persons living with HIV or TB.

Comorbidity in context: Part 1. Medical considerations around HIV and tuberculosis during the COVID-19 pandemic in South Africa

Infectious diseases pandemics have devastating health, social and economic consequences, especially in developing countries such as South Africa. Scarce medical resources must often be rationed effectively to contain the disease outbreak. In the case of COVID-19, even the best-resourced countries will have inadequate intensive care facilities for the large number of patients needing admission and ventilation. The scarcity of medical resources creates the need for national governments to establish admission criteria that are evidence-based and fair. Questions have been raised whether infection with HIV or tuberculosis (TB) may amplify the risk of adverse COVID-19 outcomes and therefore whether these conditions should be factored in when deciding on the rationing of intensive care facilities. In light of these questions, clinical evidence regarding inclusion of these infections as comorbidities relevant to intensive care unit admission triage criteria is investigated in the first of a two-part series of articles. There is currently no evidence to indicate that HIV or TB infection on their own predispose to an increased risk of infection with SARS-CoV-2 or worse outcomes for COVID-19. It is recommended that, as for other medical conditions, validated scoring systems for poor prognostic factors should be applied. A subsequent article examines the ethicolegal implications of limiting intensive care access of persons living with HIV or TB

Comorbidity in context: Part 2. Ethicolegal considerations around HIV and tuberculosis during the COVID-19 pandemic in South Africa

The COVID-19 pandemic has brought discussions around the appropriate and fair rationing of scare resources to the forefront. This is of special importance in a country such as South Africa (SA), where scarce resources interface with high levels of need. A large proportion of the SA population has risk factors associated with worse COVID-19 outcomes. Many people are also potentially medically and socially vulnerable secondary to the high levels of infection with HIV and tuberculosis (TB) in the country. This is the second of two articles. The first examined the clinical evidence regarding the inclusion of HIV and TB as comorbidities relevant to intensive care unit (ICU) admission triage criteria. Given the fact that patients with HIV or TB may potentially be excluded from admission to an ICU on the basis of an assumption of lack of clinical suitability for critical care, in this article we explore the ethicolegal implications of limiting ICU access of persons living with HIV or TB. We argue that all allocation and rationing decisions must be in terms of SA law, which prohibits unfair discrimination. In addition, ethical decision-making demands accurate and evidence-based strategies for the fair distribution of limited resources. Rationing decisions and processes should be fair and based on visible and consistent criteria that can be subjected to objective scrutiny, with the ultimate aim of ensuring accountability, equity and fairness

Delayed disease progression in HIV-2: the importance of TRIM5α and the retroviral capsid.

HIV-2 is thought to have entered the human population in the 1930s through cross-species transmission of SIV from sooty mangabeys in West Africa. Unlike HIV-1, HIV-2 has not led to a global pandemic, and recent data suggest that HIV-2 prevalence is declining in some West African states where it was formerly endemic. Although many early isolates of HIV-2 were derived from patients presenting with AIDS-defining illnesses, it was noted that a much larger proportion of HIV-2-infected subjects behaved as long-term non-progressors (LTNP) than their HIV-1-infected counterparts. Many HIV-2-infected adults are asymptomatic, maintaining an undetectable viral load for over a decade. However, despite lower viral loads, HIV-2 progresses to clinical AIDS without therapeutic intervention in most patients. In addition, successful treatment with anti-retroviral therapy (ART) is more challenging than for HIV-1. HIV-2 is significantly more sensitive to restriction by host restriction factor tripartite motif TRIM5α than HIV-1, and this difference in sensitivity is linked to differences in capsid structure. In this review we discuss the determinants of HIV-2 disease progression and focus on the important interactions between TRIM5α and HIV-2 capsid in long-term viral control.