Geospatial and temporal mapping of detectable HIV-1 viral loads amid dolutegravir rollout in KwaZulu-Natal, South Africa.

South Africa rolled out dolutegravir (DTG) as first-line antiretroviral therapy (ART) in December 2019 to overcome high rates of pretreatment non-nucleoside reverse transcriptase inhibitor drug resistance. In the context of transition to DTG-based ART, this study spatiotemporally analysed detectable HIV viral loads (VLs) prior to- and following DTG rollout in public-sector healthcare facilities in KwaZulu-Natal (KZN) province, the epicentre of the HIV epidemic in South Africa. We retrospectively curated a HIV VL database using de-identified routine VL data obtained from the National Health Laboratory Service for the period January 2018 to June 2022. We analysed trends in HIV viraemia and mapped median log10 HIV VLs per facility on inverse distance weighted interpolation maps. We used Getis-Ord Gi* hotspot analysis to identify geospatial HIV hotspots. We obtained 7,639,978 HIV VL records from 736 healthcare facilities across KZN, of which 1,031,171 (13.5%) had detectable VLs (i.e., VLs ≥400 copies/millilitre (mL)). Of those with detectable VLs, we observed an overall decrease in HIV VLs between 2018 and 2022 (median 4.093 log10 copies/mL; 95% confidence interval (CI) 4.087-4.100 to median 3.563 log10 copies/mL; CI 3.553-3.572), p<0.01 (median test). The downward trend in proportion of HIV VLs ≥1000 copies/mL over time was accompanied by an inverse upward trend in the proportion of HIV VLs between 400 and 999 copies/mL. Moreover, specific coastal and northern districts of KZN had persistently higher VLs, with emergent hotspots demonstrating spatial clustering of high median log10 HIV VLs. The overall decrease in HIV VLs over time shows good progress towards achieving UNAIDS 95-95-95 targets in KZN, South Africa. The DTG-transition has been associated with a reduction in VLs, however, there is a need for pre-emptive monitoring of low-level viraemia. Furthermore, our findings highlight that specific districts will need intensified HIV care despite DTG rollout.

Seroprevalence of SARS-CoV-2 immunoglobulin G in HIV-positive and HIV-negative individuals in KwaZulu-Natal, South Africa.

Background: KwaZulu-Natal ranked second highest among South African provinces for the number of laboratory-confirmed cases during the second wave of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The seroprevalence of SARS-CoV-2 among certain vulnerable groups, such as people living with HIV in KwaZulu-Natal, is unknown. Objective: The study aimed to determine the prevalence of SARS-CoV-2 immunoglobulin G (IgG) in HIV-positive versus HIV-negative patients. Methods: This was a retrospective analysis of residual clinical blood specimens unrelated to coronavirus disease 2019 (COVID-19) submitted for diagnostic testing at Inkosi Albert Luthuli Central Hospital, Durban, from 10 November 2020 to 09 February 2021. Specimens were tested for SARS-CoV-2 immunoglobulin G on the Abbott Architect analyser. Results: A total of 1977/8829 (22.4%) specimens were positive for SARS-CoV-2 antibodies. Seroprevalence varied between health districts from 16.4% to 37.3%, and was 19% in HIV-positive and 35.3% in HIV-negative specimens. Seroprevalence was higher among female patients (23.6% vs 19.8%; p < 0.0001) and increased with increasing age, with a statistically significant difference between the farthest age groups (< 10 years and > 79 years; p < 0.0001). The seroprevalence increased from 17% on 10 November 2020 to 43% on 09 February 2021 during the second wave. Conclusion: Our results highlight that during the second COVID-19 wave in KwaZulu-Natal a large proportion of people living with HIV were still immunologically susceptible. The reduced seropositivity in people with virological failure further emphasises the importance of targeted vaccination and vaccine response monitoring in these individuals. What the study adds: This study contributes to data on SARS-CoV-2 seroprevalence before and during the second wave in KwaZulu-Natal, South Africa, which has the highest HIV prevalence globally. Reduced seropositivity was found among people living with HIV with virological failure, highlighting the importance of targeted booster vaccination and vaccine response monitoring.

Heterogeneity in COVID-19 infection among older persons in South Africa: Evidence from national surveillance data.

Background: The 2021 World Health Organization study on the impact of COVID-19 on older people (≥60 years) in the African region highlighted the difficulties they faced as the virus spread across borders and dominated the way of life. These difficulties included disruptions to both essential health care services and social support, as well as disconnections from family and friends. Among those who contracted COVID-19, the risks of severe illness, complications, and mortality were highest among near-old and older persons. Objective: Recognizing that older persons are a diverse group including younger- and older-aged individuals, a study was conducted to track the epidemic among near-old (50-59 years) and older persons (≥60 years) in South Africa covering the 2 years since the epidemic emerged. Methods: Using a quantitative secondary research approach, data for near-old and older persons were extracted for comparative purposes. COVID-19 surveillance outcomes (confirmed cases, hospitalizations, and deaths) and vaccination data were compiled up to March 5th, 2022. COVID-19 surveillance outcomes were plotted by epidemiological week and epidemic waves to visualize the overall growth and trajectory of the epidemic. Means for each age-group and by COVID-19 waves, together with age-specific rates, were calculated. Results: Average numbers of new COVID-19 confirmed cases and hospitalizations were highest among people aged 50-59- and 60-69-years. However, average age-specific infection rates showed that people aged 50-59 years and ≥80 years were most vulnerable to contracting COVID-19. Age-specific hospitalization and death rates increased, with people aged ≥ 70 years most affected. The number of people vaccinated was slightly higher among people aged 50-59 years before Wave Three and during Wave Four, but higher among people aged ≥ 60 years during Wave Three. The findings suggest that uptake of vaccinations stagnated prior to and during Wave Four for both age groups. Discussion: Health promotion messages and COVID-19 epidemiological surveillance and monitoring are still needed, particularly for older persons living in congregate residential and care facilities. Prompt health-seeking should be encouraged, including testing and diagnosis as well as taking up vaccines and boosters, particularly for high-risk older persons.

Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection With accumulation of mutations in a patient with poorly controlled Human Immunodeficiency Virus infection.

A 22-year-old woman with uncontrolled advanced human immunodeficiency virus (HIV) infection was persistently infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) beta variant for 9 months, the virus accumulating >20 additional mutations. Antiretroviral therapy suppressed HIV and cleared SARS-CoV-2 within 6 to 9 weeks. Increased vigilance is warranted to benefit affected individuals and prevent the emergence of novel SARS-CoV-2 variants.

Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa.

Three lineages (BA.1, BA.2 and BA.3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern predominantly drove South Africa's fourth Coronavirus Disease 2019 (COVID-19) wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and similar to BA.2 except for the addition of 69-70 deletion (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild-type amino acid at Q493. The two lineages differ only outside of the spike region. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimated growth advantages for BA.4 and BA.5 of 0.08 (95% confidence interval (CI): 0.08-0.09) and 0.10 (95% CI: 0.09-0.11) per day, respectively, over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus.

Hosting ICASA 2021 in South Africa amidst the global Omicron scare.

The 21st International Conference on HIV/AIDS and STI's in Africa (ICASA) was successfully held from the 6th to 11t h December 2021 in Durban, South Africa. Little did we know at the time of planning that COVID-19 could become such a formidable force in eroding the progress made to bring lifesaving therapies among vulnerable communities in Africa. The conference also highlighted Africa's openness to the world, also shown in the way South Africa shared data on its discovery of the Omicron variant. Arguably the most important of lessons is that integrated HIV/TB services have become a platform on which to provide other services. We also saw how HIV and TB services were used as leverage for COVID-19 services. Much was also discussed about the need to adopt more self-care approaches, as was demonstrated with the increased use of self-testing technologies for HIV, and potentially other health needs. It's clear that Africa needs to increase its capacity to support and enable innovation, particularly in the design and manufacturing of new technologies including diagnostics, vaccines and therapeutics.

Persistent Hepatitis B Viraemia with Polymerase Mutations among HIV/HBV Co-Infected Patients on HBV-Active ART in KwaZulu-Natal, South Africa.

To understand the problem of persistent Hepatitis B virus (HBV) viraemia in HIV/HBV co-infected patients on HBV-active antiretroviral therapy (ART), we assessed the rate of HBV virological response in patients on HBV-active ART in KwaZulu-Natal, South Africa, and analysed factors associated with persistent HBV viraemia. One hundred and fifty eligible participants with a chronic HBV diagnosis, with or without HIV coinfection, were enrolled and followed up after 6 months. The HBV pol gene was sequenced by next-generation sequencing and mutations were determined using the Stanford HBVseq database. Logistic regression analysis was used to assess factors associated with HBV viraemia at 6-month follow-up. The mean duration of HBV-active ART was 24 months. Thirty-seven of one hundred and six (35%) participants receiving HBV-active ART for longer than 6 months had virological failure. Advanced immunosuppression with CD4+ cell counts <200 cells/µL was independently associated with persistent HBV viraemia, aOR 5.276 (95% CI 1.575−17.670) p = 0.007. A high proportion of patients on HBV-active ART are unsuppressed, which will ultimately have an impact on global elimination goals. Better monitoring should be implemented, especially in HIV-coinfected patients with low CD4+ cell counts and followed by early HBV drug-resistance testing.

Emergence and phenotypic characterization of the global SARS-CoV-2 C.1.2 lineage.

Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The initial C.1.2 detection is associated with a high substitution rate, and includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 variants of concern or variants of interest. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta show high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2.

Reduced amplification efficiency of the RNA-dependent-RNA-polymerase target enables tracking of the Delta SARS-CoV-2 variant using routine diagnostic tests.

Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced RT-PCR amplification efficiency of the RdRp-gene target of the Seegene, Allplex 2019-nCoV diagnostic assay from June 2021 when detecting the Delta variant. We investigated whether the reduced amplification efficiency denoted by an increased RT-PCR cycle threshold value (RΔE) can be used as an indirect measure of SARS-CoV-2 Delta variant prevalence. We found a significant increase in the median RΔE for patient samples tested from June 2021, which coincided with the emergence of the SARS-CoV-2 Delta variant within our sample set. Whole genome sequencing on a subset of patient samples identified a highly conserved G15451A, non-synonymous mutation exclusively within the RdRp gene of Delta variants, which may cause reduced RT-PCR amplification efficiency. While whole genome sequencing plays an important in identifying novel SARS-CoV-2 variants, monitoring RΔE value can serve as a useful surrogate for rapid tracking of Delta variant prevalence.

HIV-1 drug resistance in adults and adolescents on protease inhibitor-based antiretroviral therapy in KwaZulu-Natal Province, South Africa.

OBJECTIVES: In low-middle-income countries, increasing levels of HIV drug resistance (HIVDR) on second-line protease inhibitor (PI)-based regimens are a cause for concern given the limited drug options for third-line antiretroviral therapy (ART). We conducted a retrospective analysis of routine HIV-1 genotyping laboratory data from KwaZulu-Natal, South Africa, to describe the frequency and patterns of HIVDR mutations and their consequent impact on standardised third-line regimens. METHODS: This was a cross-sectional analysis of all HIV-1 genotypic resistance tests conducted by the National Health Laboratory Service in KwaZulu-Natal (January 2015 to December 2016) for adults and adolescents (age ≥10 years) on second-line PI-based ART with virological failure. We assigned a third-line regimen to each record based on a national treatment algorithm and calculated the genotypic susceptibility score (GSS) for that regimen. RESULTS: Of 348 samples analysed, 287 (82.5%) had at least one drug resistance mutation (DRM) and 114 (32.8%) had at least one major PI DRM. Major PI resistance was associated with longer duration on second-line ART (aOR per 6-months = 1.11, 95% CI 1.04-1.19) and older age (aOR = 1.03, 95% CI 1.01-1.05). Of 112 patients requiring third-line ART, 12 (10.7%) had a GSS of <2 for the algorithm-assigned third-line regimen. CONCLUSION: One-third of people failing second-line ART had significant PI DRMs. A subgroup of these individuals had extensive HIVDR, where the predicted activity of third-line ART was suboptimal, highlighting the need for continuous evaluation of outcomes on third-line regimens and close monitoring for emergent HIV-1 integrase inhibitor resistance.

Cytomegalovirus pneumonia of infants in Africa: a narrative literature review.

Cytomegalovirus pneumonia has repeatedly been described in the context of HIV-exposed uninfected and HIV-infected infants. Despite its significant role in the etiology of childhood pneumonia, there is still a paucity of literature generally, and specifically in Africa, suggesting that it might be a neglected disease. Emerging evidence highlights the importance of postnatal transmission through breastmilk. The pathogenetic significance of the multiplicity of strains acquired through repeated re-infections in early infancy is unknown. The development of cheap, accurate diagnostic tools and safe, effective antivirals and the maintenance of effective prevention and treatment of pediatric HIV are needed to manage cytomegalovirus pneumonia in low-resource settings.

Detection of a SARS-CoV-2 variant of concern in South Africa.

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 importance3-5. 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 escape6-8.

Sixteen novel lineages of SARS-CoV-2 in South Africa.

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).

High incidence and persistence of hepatitis B virus infection in individuals receiving HIV care in KwaZulu-Natal, South Africa.

BACKGROUND: Hepatitis B virus (HBV), Human Immunodeficiency virus (HIV) and Tuberculosis (TB) are common infections in South Africa. We utilized the opportunity of care provision for HIV-TB co-infected patients to better understand the relationship between these coinfections, determine the magnitude of the problem, and identify risk factors for HBV infection in HIV infected patients with and without TB in KwaZulu-Natal, South Africa. METHODS: This retrospective cohort analysis was undertaken in 2018. In-care HIV infected patients were included in the analysis. Results from clinical records were analysed to determine the prevalence, incidence, persistence and factors associated with HBsAg positivity in HIV-infected patients with or without TB co-infection. RESULTS: A total of 4292 HIV-infected patients with a mean age of 34.7 years (SD: 8.8) were included. Based on HBsAg positivity, the prevalence of HBV was 8.5% (363/4292) [95% confidence interval (CI): 7.7-9.3] at baseline and 9.4% (95%CI: 8.6-10.3%) at end of follow-up. The HBV incidence rate was 2.1/100 person-years (p-y). Risk of incident HBV infection was two-fold higher among male patients (HR 2.11; 95% CI: 1.14-3.92), while severe immunosuppression was associated with a greater than two-fold higher risk of persistent infection (adjusted risk ratio (RR) 2.54; 95% CI 1.06-6.14; p = 0.004. Additionally, active TB at enrolment was associated with a two-fold higher risk of incident HBV infection (aHR 2.38; 95% CI: 0.77-7.35). CONCLUSION: The provision of HIV care and treatment in high HBV burden settings provide a missed opportunity for HBV screening, immunization and care provision.

High rate of occult hepatitis B virus infection in hemodialysis units of KwaZulu-Natal, South Africa.

Occult hepatitis B virus (HBV) infection (OBI) is defined as the presence of HBV DNA in the liver with or without detectable HBV DNA in the serum of individuals testing HBV surface antigen (HBsAg) negative using currently available assays. The prevalence of OBI among patients receiving hemodialysis (HD) treatment remains poorly characterized in South Africa despite the high prevalence of HBV. We sought to determine the prevalence of OBI in HD units in tertiary hospitals of KwaZulu-Natal and to characterize the HBV S gene mutations potentially responsible for OBI. A cross-sectional descriptive study of residual diagnostic plasma samples from 85 HBsAg-negative patients receiving HD treatment was included. The PreS/S gene was amplified with a nested HBV polymerase chain reaction for downstream next-generation sequencing, to determine the viral genotype and identify S gene mutations associated with OBI. Nine of the 85 samples had OBI, based on detectable HBV DNA. The point prevalence of OBI was 10.6% (95% control interval: 5.5%-19.1%). Phylogenetic analysis of the samples with OBI showed that all belonged to genotype A. Three (~33%) samples had mutations in the major hydrophilic region (MHR) within the S gene, three (~33%) had mutations within the S gene but outside the MHR, whilst the remaining three had no mutations observed. The prevalence of OBI in HBsAg-negative patients undergoing HD was 10.6%, suggesting that OBI is a clinically significant problem in patients with HD in this region. The screening methods for HBV infection need to be revised to include nucleic acid testing.