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Social distancing measures to address the US coronavirus disease 2019 (COVID-19) epidemic may have notable health and social impacts. We conducted a longitudinal pretest-posttest comparison group study to estimate the change in COVID-19 case growth before versus after implementation of statewide social distancing measures in the US. The primary exposure was time before (14 days prior to, and through 3 days after) versus after (beginning 4 days after, to up to 21 days after) implementation of the first statewide social distancing measures. Statewide restrictions on internal movement were examined as a secondary exposure. The primary outcome was the COVID-19 case growth rate. The secondary outcome was the COVID-19-attributed mortality growth rate. All states initiated social distancing measures between March 10 and March 25, 2020. The mean daily COVID-19 case growth rate decreased beginning 4 days after implementation of the first statewide social distancing measures, by 0.9% per day (95% CI -1.4% to -0.4%; P < 0.001). We did not observe a statistically significant difference in the mean daily case growth rate before versus after implementation of statewide restrictions on internal movement (0.1% per day; 95% CI -0.04% to 0.3%; P = 0.14), but there is substantial difficulty in disentangling the unique associations with statewide restrictions on internal movement from the unique associations with the first social distancing measures. Beginning 7 days after social distancing, the COVID-19-attributed mortality growth rate decreased by 2.0% per day (95% CI -3.0% to -0.9%; P < 0.001). Our analysis is susceptible to potential bias resulting from the aggregate nature of the ecological data, potential confounding by contemporaneous changes (e.g., increases in testing), and potential underestimation of social distancing due to spillover effects from neighboring states. Statewide social distancing measures were associated with a decrease in the COVID-19 case growth rate that was statistically significant. Statewide social distancing measures were also associated with a decrease in the COVID-19-attributed mortality growth rate beginning 7 days after implementation, although this decrease was no longer statistically significant by 10 days.

Outpatients with Covid-19 were followed serially with frequent PCR and viral-culture assessments. The SARS-CoV-2 omicron (BA.1) variant could be cultured a median of 8 days after symptom onset or the initial positive test.

  [...]mortality had to be estimated among those lost to follow up [9,10]. Because persons in HIV treatment programs are much more likely to be lost to care than confirmed as dead [15,16], and because the vast majority of HIV-related mortality events go unreported [17], the mortality estimates in these studies are likely to be biased. [...]perhaps most notably, none of these studies directly observed non-HIV mortality. [...]while they were able to document trends in mortality among persons with HIV, they were unable to assess the extent to which these changes were related to HIV care or to unrelated secular trends in health and health behavior.

ObjectivesWe evaluated whether implementation of lockdown orders in South Africa affected ambulatory clinic visitation in rural Kwa-Zulu Natal (KZN).DesignObservational cohortSettingData were analysed from 11 primary healthcare clinics in northern KZN.ParticipantsA total of 46 523 individuals made 89 476 clinic visits during the observation period.Exposure of interestWe conducted an interrupted time series analysis to estimate changes in clinic visitation with a focus on transitions from the prelockdown to the level 5, 4 and 3 lockdown periods.Outcome measuresDaily clinic visitation at ambulatory clinics. In stratified analyses, we assessed visitation for the following subcategories: child health, perinatal care and family planning, HIV services, non-communicable diseases and by age and sex strata.ResultsWe found no change in total clinic visits/clinic/day at the time of implementation of the level 5 lockdown (change from 90.3 to 84.6 mean visits/clinic/day, 95% CI −16.5 to 3.1), or at the transitions to less stringent level 4 and 3 lockdown levels. We did detect a >50% reduction in child healthcare visits at the start of the level 5 lockdown from 11.9 to 4.7 visits/day (−7.1 visits/clinic/day, 95% CI −8.9 to 5.3), both for children aged <1 year and 1–5 years, with a gradual return to prelockdown within 3 months after the first lockdown measure. In contrast, we found no drop in clinic visitation in adults at the start of the level 5 lockdown, or related to HIV care (from 37.5 to 45.6, 8.0 visits/clinic/day, 95% CI 2.1 to 13.8).ConclusionsIn rural KZN, we identified a significant, although temporary, reduction in child healthcare visitation but general resilience of adult ambulatory care provision during the first 4 months of the lockdown. Future work should explore the impacts of the circulating epidemic on primary care provision and long-term impacts of reduced child visitation on outcomes in the region.

Little is known about the impact of pretreatment drug resistance (PDR) on the efficacy of second generation integrase inhibitors. We sequenced pretreatment plasma specimens from the ADVANCE trial (NCT03122262). Our primary outcome was 96-week virologic success, defined as a sustained viral load <1000 copies/mL from 12 weeks onwards, <200 copies/mL from 24 weeks onwards, and <50 copies/mL after 48 weeks. Here we report how this outcome was impacted by PDR, defined by the World Health Organization (WHO) mutation list. Of 1053 trial participants, 874 (83%) have successful sequencing, including 289 (33%) randomized to EFV-based therapy and 585 (67%) randomized to DTG-based therapy. Fourteen percent (122/874) have ≥1 WHO-defined mutation, of which 98% (120/122) are NNRTI mutations. Rates of virologic suppression are lower in the total cohort among those with PDR 65% (73/112) compared to those without PDR (85% [605/713], P < 0.001), and for those on EFV-based treatment (60% [12/20] vs 86% [214/248], P = 0.002) and for those on DTG-based treatment (61/92 [66%] vs 84% [391/465] P < 0.001, P for interaction by regimen 0.49). Results are similar in multivariable models adjusted for clinical characteristics and adherence. NNRTI resistance prior to treatment is associated with long-term failure of integrase inhibitor-containing first-line regimens, and portends high rates of first-line failure in sub Saharan Africa. Here the authors combine next generation sequencing on plasma from participants of the ADVANCE clinical trial with virological and follow-up data to investigate the impact of pre-treatment drug resistance (PDR) to non-nucleoside reverse transcriptase inhibitors (NNRTIs) on the efficacy of second-generation integrase inhibitors and find an association between NNRTI resistance prior to treatment and long-term treatment.

Low- and middle-income countries are implementing COVID-19 vaccination strategies in light of varying vaccine efficacies and costs, supply shortages, and resource constraints. Here, we use a microsimulation model to evaluate clinical outcomes and cost-effectiveness of a COVID-19 vaccination program in South Africa. We varied vaccination coverage, pace, acceptance, effectiveness, and cost as well as epidemic dynamics. Providing vaccines to at least 40% of the population and prioritizing vaccine rollout prevented >9 million infections and >73,000 deaths and reduced costs due to fewer hospitalizations. Model results were most sensitive to assumptions about epidemic growth and prevalence of prior immunity to SARS-CoV-2, though the vaccination program still provided high value and decreased both deaths and health care costs across a wide range of assumptions. Vaccination program implementation factors, including prompt procurement, distribution, and rollout, are likely more influential than characteristics of the vaccine itself in maximizing public health benefits and economic efficiency. Cost, supply and logistics present challenges to COVID-19 vaccine rollout in low and middle income countries. Here, the authors model vaccination programmes in South Africa and demonstrate the importance of the pace of vaccine rollout, with even moderately efficacious vaccines likely to be cost-effective.

ObjectiveTo assess the effect of lockdown during the 2020 COVID-19 pandemic on daily all-cause admissions, and by age and diagnosis subgroups, and the odds of all-cause mortality in a hospital in rural KwaZulu-Natal (KZN).DesignObservational cohort.SettingReferral hospital for 17 primary care clinics in uMkhanyakude District.ParticipantsData collected by the Africa Health Research Institute on all admissions from 1 January to 20 October: 5848 patients contributed to 6173 admissions.ExposureFive levels of national lockdown in South Africa from 27 March 2020, with restrictions decreasing from levels 5 to 1, respectively.Outcome measuresChanges and trends in daily all-cause admissions and risk of in-hospital mortality before and at each stage of lockdown, estimated by Poisson and logistic interrupted time series regression, with stratification for age, sex and diagnosis.ResultsDaily admissions decreased during level 5 lockdown for infants (incidence rate ratio (IRR) compared with prelockdown 0.63, 95% CI 0.44 to 0.90), children aged 1–5 years old (IRR 0.43, 95% CI 028 to 0.65) and respiratory diagnoses (IRR 0.57, 95% CI 0.36 to 0.90). From level 4 to level 3, total admissions increased (IRR 1.17, 95% CI 1.06 to 1.28), as well as for men >19 years (IRR 1.50, 95% CI 1.17 to 1.92) and respiratory diagnoses (IRR 4.26, 95% CI 2.36 to 7.70). Among patients admitted to hospital, the odds of death decreased during level 5 compared with prelockdown (adjusted OR 0.48, 95% CI 0.28 to 0.83) and then increased in later stages.ConclusionsLevel 5 lockdown is likely to have prevented the most vulnerable population, children under 5 years and those more severely ill from accessing hospital care in rural KZN, as reflected by the drop in admissions and odds of mortality. Subsequent increases in admissions and in odds of death in the hospital could be due to improved and delayed access to hospital as restrictions were eased.

HIV-associated changes in intestinal microbiota are believed to be important drivers of disease progression. However, the majority of studies have focused on populations in high-income countries rather than in developing regions where HIV burden is greatest. To better understand the impact of HIV on fecal microbiota globally, we compare the fecal microbial community of individuals in the U.S., Uganda, and Botswana. We identify significant bacterial taxa alterations with both treated and untreated HIV infection with a high degree of uniqueness in each cohort. HIV-associated taxa alterations are also significantly different between populations that report men who have sex with men (MSM) behavior and non-MSM populations. Additionally, while we find that HIV infection is consistently associated with higher soluble markers of immune activation, most specific bacterial taxa associated with these markers in each region are not shared and none are shared across all three geographic locations in our study. Our findings demonstrate that HIV-associated changes in fecal microbiota are overall distinct among geographical locations and sexual behavior groups, although a small number of taxa shared between pairs of geographic locations warrant further investigation, highlighting the importance of considering host context to fully assess the impact of the gut microbiome on human health and disease. Here, the authors compare the fecal microbial community of individuals in the U.S., Uganda, and Botswana, and identify significant bacterial taxa alterations with both treated and untreated HIV infection although with a high degree of uniqueness in each cohort, and also significant differences between populations that report men who have sex with men (MSM) behavior and non-MSM populations.

Despite expanded antiretroviral therapy (ART) in South Africa, HIV-1 transmission persists. Integrase strand transfer inhibitors (INSTI) and long-acting injectables offer potential for superior viral suppression, but pre-existing drug resistance could threaten their effectiveness. In a community-based study in rural KwaZulu-Natal, prior to widespread INSTI usage, we enroled 18,025 individuals to characterise HIV-1 drug resistance and transmission networks to inform public health strategies. HIV testing and reflex viral load quantification were performed, with deep sequencing (20% variant threshold) used to detect resistance mutations. Phylogenetic and geospatial analyses characterised transmission clusters. One-third of participants were HIV-positive, with 21.7% having detectable viral loads; 62.1% of those with detectable viral loads were ART-naïve. Resistance to older reverse transcriptase (RT)-targeting drugs was found, but INSTI resistance remained low (<1%). Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, particularly to rilpivirine (RPV) even in ART-naïve individuals, was concerning. Twenty percent of sequenced individuals belonged to transmission clusters, with geographic analysis highlighting higher clustering in peripheral and rural areas. Our findings suggest promise for INSTI-based strategies in this setting but underscore the need for RPV resistance screening before implementing long-acting cabotegravir (CAB) + RPV. The significant clustering emphasises the importance of geographically targeted interventions to effectively curb HIV-1 transmission. There is limited data on drug resistance in South African communities strongly affected by HIV. In this study, the authors observed low levels of resistance to newer drugs but widespread resistance to older HIV medications in a South African community. Resistance to rilpivirine was detected even in untreated individuals.

* The international response to the West African Ebola virus disease epidemic has exemplified the great potential of the global public health community. However, the protracted early response also revealed critical gaps, which likely resulted in exacerbation of the epidemic.