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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.
Summary
Background
Global HIV programs continue to experience challenges achieving the
high rates of HIV testing and treatment needed to optimize health and reduce
transmission. Botswana represents a useful “demonstration
case” in assessing the feasibility of achieving the new UNAIDS
targets for 2020: 90% of all persons living with HIV knowing their status,
90% of these individuals receiving sustained antiretroviral treatment (ART),
and 90% of those on ART having virologic suppression
(“90–90–90”).
Methods
A population-based random sample of individuals was recruited and
interviewed in 30 rural and peri-urban communities from October 2013 to
November 2015 in Botswana as part of a large, ongoing PEPFAR-funded
community-randomized trial designed to evaluate the impact of a combination
prevention package on HIV incidence. A random sample of approximately 20% of
households in each of these 30 communities was selected. Consenting
household residents aged 16–64 years who were Botswana citizens or
spouses of citizens responded to a questionnaire and had blood drawn for HIV
testing in absence of documentation of positive HIV status. HIV-1 RNA
testing was performed in all HIV-infected participants, regardless of
treatment status.
Findings
Eighty-one percent of enumerated eligible household members took part
in the survey (10% refused and 9% were absent). Among 12,610 participants
surveyed, 3,596 (29%) were HIV infected; 2,995 (83·3%) of these
individuals already knew their HIV status. Among those who knew their HIV
status, 2,617 (87·4%) were currently receiving ART (this represented
95% of those eligible for ART by current Botswana national guidelines, and
73% of all HIV-infected persons). We obtained an HIV-1 RNA result in
99·7% of HIV-infected participants. Of the 2,609 individuals
currently receiving ART with a viral load measurement, 2,517 (96·5%)
had HIV-1 RNA ≤400 copies/mL. Overall, 70·2% of HIV-infected
persons had virologic suppression, close to the UNAIDS target of 73%.
Results of three sensitivity analyses to account for possible uncertainty
due to non-participation and under-representation of urban areas, revealed
somewhat lower, but nevertheless remarkably high 90–90–90
coverage.
Interpretation
Botswana, a resource-constrained setting with high HIV prevalence,
appears to have achieved very high rates of HIV testing, treatment coverage,
and virologic suppression for those on ART in this population-based survey,
despite the Botswana ART initiation threshold of ≤350
cells/mm3. These findings provide evidence that the UNAIDS
90-90-90 targets, while ambitious, are achievable even in
resource-constrained settings with high HIV burden.
Funding
The United States President’s Emergency Plan for AIDS Relief
(PEPFAR) through the Centers for Disease Control and Prevention (CDC).
BACKGROUND-The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown.METHODS-We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios.
South Africa’s fourth COVID-19 wave was driven predominantly by three lineages (BA.1, BA.2 and BA.3) of the SARS-CoV-2 Omicron variant of concern. We have now identified two new lineages, BA.4 and BA.5. The spike proteins of BA.4 and BA.5 are identical, and comparable to BA.2 except for the addition of 69-70del, L452R, F486V and the wild type amino acid at Q493. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure with the TaqPath™ COVID-19 qPCR assay. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa from the first week of April 2022 onwards. Using a multinomial logistic regression model, we estimate growth advantages for BA.4 and BA.5 of 0.08 (95% CI: 0.07 - 0.09) and 0.12 (95% CI: 0.09 - 0.15) per day respectively over BA.2 in South Africa.
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