HIV, multimorbidity, and health-related quality of life in rural KwaZulu-Natal, South Africa: A population-based study.

Health-related quality of life (HRQoL) assesses the perceived impact of health status across life domains. Although research has explored the relationship between specific conditions, including HIV, and HRQoL in low-resource settings, less attention has been paid to the association between multimorbidity and HRQoL. In a secondary analysis of cross-sectional data from the Vukuzazi ("Wake up and know ourselves" in isiZulu) study, which identified the prevalence and overlap of non-communicable and infectious diseases in the uMkhanyakunde district of KwaZulu-Natal, we (1) evaluated the impact of multimorbidity on HRQoL; (2) determined the relative associations among infectious diseases, non-communicable diseases (NCDs), and HRQoL; and (3) examined the effects of controlled versus non-controlled disease on HRQoL. HRQoL was measured using the EQ-5D-3L, which assesses overall perceived health, five specific domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and three levels of problems (no problems, some problems, and extreme problems). Six diseases and disease states were included in this analysis: HIV, diabetes, stroke, heart attack, high blood pressure, and TB. After examining the degree to which number of conditions affects HRQoL, we estimated the effect of joint associations among combinations of diseases, each HRQoL domain, and overall health. Then, in one set of ridge regression models, we assessed the relative impact of HIV, diabetes, stroke, heart attack, high blood pressure, and tuberculosis on the HRQoL domains; in a second set of models, the contribution of treatment (controlled vs. uncontrolled disease) was added. A total of 14,008 individuals were included in this analysis. Having more conditions adversely affected perceived health (r = -0.060, p<0.001, 95% CI: -0.073 to -0.046) and all HRQoL domains. Infectious conditions were related to better perceived health (r = 0.051, p<0.001, 95% CI: 0.037 to 0.064) and better HRQoL, whereas non-communicable diseases (NCDs) were associated with worse perceived health (r = -0.124, p<0.001, -95% CI: 0.137 to -0.110) and lower HRQoL. Particular combinations of NCDs were detrimental to perceived health, whereas HIV, which was characterized by access to care and suppressed viral load in the large majority of those affected, was counterintuitively associated with better perceived health. With respect to disease control, unique combinations of uncontrolled NCDs were significantly related to worse perceived health, and controlled HIV was associated with better perceived health. The presence of controlled and uncontrolled NCDs was associated with poor perceived health and worse HRQoL, whereas the presence of controlled HIV was associated with improved HRQoL. HIV disease control may be critical for HRQoL among people with HIV, and incorporating NCD prevention and attention to multimorbidity into healthcare strategies may improve HRQoL.

SARS-CoV-2 viral clearance and evolution varies by type and severity of immunodeficiency.

Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent coronavirus disease 2019 (COVID-19) remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median times to nasal viral RNA and culture clearance in individuals with severe immunosuppression due to hematologic malignancy or transplant (S-HT) were 72 and 40 days, respectively, both of which were significantly longer than clearance rates in individuals with severe immunosuppression due to autoimmunity or B cell deficiency (S-A), individuals with nonsevere immunodeficiency, and nonimmunocompromised groups (P < 0.01). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing resistance against therapeutic monoclonal antibodies. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral responses, whereas only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across distinct immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.

HIV, Social Networks, and Loneliness among Older Adults in Uganda.

Loneliness among older adults has been identified as a major public health problem. Yet little is known about loneliness, or the potential role of social networks in explaining loneliness, among older people with HIV (PWH) in sub-Saharan Africa, where 70% of PWH reside. To explore this issue, we analyzed data from 599 participants enrolled in the Quality of Life and Ageing with HIV in Rural Uganda study, including older adults with HIV in ambulatory care and a comparator group of people without HIV of similar age and gender. The 3-item UCLA Loneliness Scale was used to measure loneliness, and HIV status was the primary explanatory variable. The study found no statistically significant correlation between loneliness and HIV status. However, individuals with HIV had smaller households, less physical and financial support, and were less socially integrated compared to those without HIV. In multivariable logistic regressions, loneliness was more likely among individuals who lived alone (aOR:3.38, 95% CI:1.47-7.76) and less likely among those who were married (aOR:0.34, 95% CI:0.22-0.53) and had a higher level of social integration (aOR:0.86, 95% CI: 0.79-0.92). Despite having smaller social networks and less support, older adults with HIV had similar levels of loneliness as those without HIV, which may be attributed to resiliency and access to HIV-related health services among individuals with HIV. Nonetheless, further research is necessary to better understand the mechanisms involved.

SARS-CoV-2 Virologic Rebound With Nirmatrelvir-Ritonavir Therapy : An Observational Study.

BACKGROUND: Data are conflicting regarding an association between treatment of acute COVID-19 with nirmatrelvir-ritonavir (N-R) and virologic rebound (VR). OBJECTIVE: To compare the frequency of VR in patients with and without N-R treatment for acute COVID-19. DESIGN: Observational cohort study. SETTING: Multicenter health care system in Boston, Massachusetts. PARTICIPANTS: Ambulatory adults with acute COVID-19 with and without use of N-R. INTERVENTION: Receipt of 5 days of N-R treatment versus no COVID-19 therapy. MEASUREMENTS: The primary outcome was VR, defined as either a positive SARS-CoV-2 viral culture result after a prior negative result or 2 consecutive viral loads above 4.0 log10 copies/mL that were also at least 1.0 log10 copies/mL higher than a prior viral load below 4.0 log10 copies/mL. RESULTS: Compared with untreated persons (n = 55), those taking N-R (n = 72) were older, received more COVID-19 vaccinations, and more commonly had immunosuppression. Fifteen participants (20.8%) taking N-R had VR versus 1 (1.8%) who was untreated (absolute difference, 19.0 percentage points [95% CI, 9.0 to 29.0 percentage points]; P = 0.001). All persons with VR had a positive viral culture result after a prior negative result. In multivariable models, only N-R use was associated with VR (adjusted odds ratio, 10.02 [CI, 1.13 to 88.74]; P = 0.038). Virologic rebound was more common among those who started therapy within 2 days of symptom onset (26.3%) than among those who started 2 or more days after symptom onset (0%) (P = 0.030). Among participants receiving N-R, those who had VR had prolonged shedding of replication-competent virus compared with those who did not have VR (median, 14 vs. 3 days). Eight of 16 participants (50% [CI, 25% to 75%]) with VR also reported symptom rebound; 2 were completely asymptomatic. No post-VR resistance mutations were detected. LIMITATIONS: Observational study design with differences between the treated and untreated groups; positive viral culture result was used as a surrogate marker for risk for ongoing viral transmission. CONCLUSION: Virologic rebound occurred in approximately 1 in 5 people taking N-R, often without symptom rebound, and was associated with shedding of replication-competent virus. PRIMARY FUNDING SOURCE: National Institutes of Health.

SARS-CoV-2 virologic rebound with nirmatrelvir-ritonavir therapy.

Objective: To compare the frequency of replication-competent virologic rebound with and without nirmatrelvir-ritonavir treatment for acute COVID-19. Secondary aims were to estimate the validity of symptoms to detect rebound and the incidence of emergent nirmatrelvir-resistance mutations after rebound. Design: Observational cohort study. Setting: Multicenter healthcare system in Boston, Massachusetts. Participants: We enrolled ambulatory adults with a positive COVID-19 test and/or a prescription for nirmatrelvir-ritonavir. Exposures: Receipt of 5 days of nirmatrelvir-ritonavir treatment versus no COVID-19 therapy. Main Outcome and Measures: The primary outcome was COVID-19 virologic rebound, defined as either (1) a positive SARS-CoV-2 viral culture following a prior negative culture or (2) two consecutive viral loads ≥4.0 log10 copies/milliliter after a prior reduction in viral load to <4.0 log10 copies/milliliter. Results: Compared with untreated individuals (n=55), those taking nirmatrelvir-ritonavir (n=72) were older, received more COVID-19 vaccinations, and were more commonly immunosuppressed. Fifteen individuals (20.8%) taking nirmatrelvir-ritonavir experienced virologic rebound versus one (1.8%) of the untreated (absolute difference 19.0% [95%CI 9.0-29.0%], P=0.001). In multivariable models, only N-R was associated with VR (AOR 10.02, 95%CI 1.13-88.74). VR occurred more commonly among those with earlier nirmatrelvir-ritonavir initiation (29.0%, 16.7% and 0% when initiated days 0, 1, and ≥2 after diagnosis, respectively, P=0.089). Among participants on N-R, those experiencing rebound had prolonged shedding of replication-competent virus compared to those that did not rebound (median: 14 vs 3 days). Only 8/16 with virologic rebound reported worsening symptoms (50%, 95%CI 25%-75%); 2 were completely asymptomatic. We detected no post-rebound nirmatrelvir-resistance mutations in the NSP5 protease gene. Conclusions and Relevance: Virologic rebound occurred in approximately one in five people taking nirmatrelvir-ritonavir and often occurred without worsening symptoms. Because it is associated with replication-competent viral shedding, close monitoring and potential isolation of those who rebound should be considered.

Associations of the COVID-19 pandemic with quality of life: A cross-sectional study of older-age people with and without HIV in rural Uganda.

Background: COVID-19-related lockdowns and other public health measures may have differentially affected the quality of life (QOL) of older people with and without human immunodeficiency virus (HIV) in rural Uganda. Methods: The Quality of Life and Aging with HIV in Rural Uganda study enrolled people with and without HIV aged over 49 from October 2020 to October 2021. We collected data on COVID-19-related stressors (behavior changes, concerns, interruptions in health care, income, and food) and the participants' QOL. We used linear regression to estimate the associations between COVID-19-related stressors and QOL, adjusting for demographic characteristics, mental and physical health, and time before vs after the lockdown during the second COVID-19 wave in Uganda. Interaction between HIV and COVID-19-related stressors evaluated effect modification. Results: We analyzed complete data from 562 participants. Mean age was 58 (standard deviation (SD) = 7); 265 (47%) participants were female, 386 (69%) were married, 279 (50%) had HIV, and 400 (71%) were farmers. Those making ≥5 COVID-19-related behavior changes compared to those making ≤2 had worse general QOL (estimated linear regression coefficient (b) = - 4.77; 95% confidence interval (CI) = -6.61, -2.94) and health-related QOL (b = -4.60; 95% CI = -8.69, -0.51). Having access to sufficient food after the start of the COVID-19 pandemic (b = 3.10, 95% CI = 1.54, 4.66) and being interviewed after the start of the second lockdown (b = 2.79, 95% CI = 1.30, 4.28) were associated with better general QOL. Having HIV was associated with better health-related QOL (b = 5.67, 95% CI = 2.91,8.42). HIV was not associated with, nor did it modify the association of COVID-19-related stressors with general QOL. Conclusions: In the context of the COVID-19 pandemic in an HIV-endemic, low-resource setting, there was reduced QOL among older Ugandans making multiple COVID-19 related behavioral changes. Nonetheless, good QOL during the second COVID-19 wave may suggest resilience among older Ugandans.

The benefits of care: treated HIV infection and health-related quality of life among older-aged people in Uganda.

OBJECTIVES: The objective of this study is to explore how HIV care affects health-related quality of life (HRQoL) among older people in Uganda. METHODS: We enrolled older-aged (≥49 years) people with HIV receiving HIV care and treatment, along with age- and sex-similar people without HIV. We measured health-related quality of life using the EQ-5D-3L scale. RESULTS: People with HIV (n = 298) and people without HIV (n = 302) were similar in median age (58.4 vs. 58.5 years), gender, and number of comorbidities. People with HIV had higher self-reported health status (b = 7.0; 95% confidence interval [CI], 4.2-9.7), higher EQ-5D utility index (b = 0.05; 95% CI, 0.02-0.07), and were more likely to report no problems with self-care (adjusted odds ratio [AOR], 2.0; 95% CI, 1.2-3.3) or pain/discomfort (AOR = 1.8, 95% CI, 1.3-2.8). Relationships between HIV serostatus and health-related quality of life differed by gender, but not age. CONCLUSIONS: Older people with HIV receiving care and treatment reported higher health-related quality of life than people without HIV in Uganda. Access to primary care through HIV programs and/or social network mobilization may explain this difference, but further research is needed to elucidate the mechanisms.

Characterization of Virologic Rebound Following Nirmatrelvir-Ritonavir Treatment for Coronavirus Disease 2019 (COVID-19).

We enrolled 7 individuals with recurrent symptoms or antigen test conversion following nirmatrelvir-ritonavir treatment. High viral loads (median 6.1 log10 copies/mL) were detected after rebound for a median of 17 days after initial diagnosis. Three had culturable virus for up to 16 days after initial diagnosis. No known resistance-associated mutations were identified.

Vaccine breakthrough infection leads to distinct profiles of neutralizing antibody responses by SARS-CoV-2 variant.

Protective immunity against SARS-CoV-2 infection after COVID-19 vaccination may differ by variant. We enrolled vaccinated (n = 39) and unvaccinated (n = 11) individuals with acute, symptomatic SARS-CoV-2 Delta or Omicron infection and performed SARS-CoV-2 viral load quantification, whole-genome sequencing, and variant-specific antibody characterization at the time of acute illness and convalescence. Viral load at the time of infection was inversely correlated with antibody binding and neutralizing antibody responses. Across all variants tested, convalescent neutralization titers in unvaccinated individuals were markedly lower than in vaccinated individuals. Increases in antibody titers and neutralizing activity occurred at convalescence in a variant-specific manner. For example, among individuals infected with the Delta variant, neutralizing antibody responses were weakest against BA.2, whereas infection with Omicron BA.1 variant generated a broader response against all tested variants, including BA.2.

Antiretroviral therapy adherence patterns, virological suppression, and emergence of drug resistance: A nested case-control study from Uganda and South Africa.

BACKGROUND: Relationships between distinct antiretroviral therapy (ART) adherence patterns and risk of drug resistance are not well understood. METHODS: We conducted a nested case-control analysis within a longitudinal cohort study of individuals initiating efavirenz-based ART. Primary outcomes of interest, measured at 6 and 12 months after treatment initiation, were: 1) virologic suppression, 2) virologic failure with resistance, and 3) virologic failure without resistance. Our primary exposure of interest was ART adherence, measured over the 6 months before each visit with electronic pill monitors, and categorized in three ways: 1) 6 months average adherence; 2) running adherence, defined as the proportion of days with average adherence over 9 days of less than or equal to 10%, 20%, and 30%; and 3) number of 3-, 7-, and 28-day treatment gaps in the prior 6 months. RESULTS: We analyzed data from 166 individuals (107 had virologic failure during observation and 59 had virologic suppression at 6 and 12 months). Average adherence was higher among those with virologic suppression (median 83%, IQR 58-96%) versus those with virologic failure with resistance (median 35%, IQR 20-77%, pairwise P < 0.01) and those with virologic failure without resistance (median 21%, IQR 2-54%, pairwise P < 0.01). Although treatment gaps generally predicted virologic failure (P < 0.01), they did not differentiate failure with and without drug resistance (P > 0.6). CONCLUSIONS: Average adherence patterns, but not the assessed frequency of treatment gaps, differentiated failure with versus without drug resistance among individuals initiating efavirenz-based ART. Future work should explore adherence-resistance relationships for integrase inhibitor-based regimens.

Priorities for health and wellbeing for older people with and without HIV in Uganda: a qualitative methods study.

INTRODUCTION: With improved HIV treatment availability in sub-Saharan Africa, the population of older people with HIV (PWH) is growing. In this qualitative study, we intended to understand (1) the lived experiences of ageing people in rural Uganda, with and without HIV, (2) their fears and health priorities as they grow older. METHODS: We conducted 36 semi-structured interviews with individuals with and without HIV in Mbarara, Uganda from October 2019 to February 2020. Interview guide topics included priorities in older age, physical functioning in daily activities, social functioning, HIV-related stigma and the impact of multimorbidity on health and independence. Interviews were conducted in Runyankole, transcribed, translated and inductively coded thematically by two researchers with tests for inter-coder reliability. RESULTS: The respondents were purposively sampled to be evenly divided by sex and HIV serostatus. The median age of respondents was 57 (49-73). Two-thirds were married or cohabitating, 94% had biological children and 75% cited farming as their primary livelihood. Overall, PWH considered themselves as healthy or healthier than people without HIV (PWOH). PWH rarely considered their HIV status a barrier to a healthy life, but some reported a constant sense of anxiety as it relates to their long-term health. Irrespective of HIV status, nearly all respondents noted concerns about memory loss, physical pain, reductions in energy and the effect of these changes on their ability to complete physical tasks like small-scale farming, and activities of daily living important to the quality of life, such as participating in community groups. Increasing reliance on others for social, physical and financial support was also a common theme. The most prevalent health concern among participants involved the threat of non-communicable diseases and perceptions that physical functioning may diminish. CONCLUSIONS: In rural Uganda, we found that PWH consider themselves to be healthy and do not anticipate a different ageing experience from PWOH. Common priorities shared by both groups included the desire for physical and financial independence, health maintenance and social support for daily functioning and social needs. Entities supporting geriatric care in Uganda would benefit from attention to concerns about functional limitations and reported needs as people age with and without HIV.

Duration of viable virus shedding in SARS-CoV-2 omicron variant infection.

Clinical features of SARS-CoV-2 Omicron variant infection, including incubation period and transmission rates, distinguish this variant from preceding variants. However, whether the duration of shedding of viable virus differs between omicron and previous variants is not well understood. To characterize how variant and vaccination status impact shedding of viable virus, we serially sampled symptomatic outpatients newly diagnosed with COVID-19. Anterior nasal swabs were tested for viral load, sequencing, and viral culture. Time to PCR conversion was similar between individuals infected with the Delta and the Omicron variant. Time to culture conversion was also similar, with a median time to culture conversion of 6 days (interquartile range 4-8 days) in both groups. There were also no differences in time to PCR or culture conversion by vaccination status.

Vaccine Breakthrough Infection with the SARS-CoV-2 Delta or Omicron (BA.1) Variant Leads to Distinct Profiles of Neutralizing Antibody Responses.

There is increasing evidence that the risk of SARS-CoV-2 infection among vaccinated individuals is variant-specific, suggesting that protective immunity against SARS-CoV-2 may differ by variant. We enrolled vaccinated (n = 39) and unvaccinated (n = 11) individuals with acute, symptomatic SARS-CoV-2 Delta or Omicron infection and performed SARS-CoV-2 viral load quantification, whole-genome sequencing, and variant-specific antibody characterization at the time of acute illness and convalescence. Viral load at the time of infection was inversely correlated with antibody binding and neutralizing antibody responses. Increases in antibody titers and neutralizing activity occurred at convalescence in a variant-specific manner. Across all variants tested, convalescent neutralization titers in unvaccinated individuals were markedly lower than in vaccinated individuals. For individuals infected with the Delta variant, neutralizing antibody responses were weakest against BA.2, whereas infection with Omicron BA.1 variant generated a broader response against all tested variants, including BA.2.

Determining the Incidence of Asymptomatic SARS-CoV-2 Among Early Recipients of COVID-19 Vaccines (DISCOVER-COVID-19): A Prospective Cohort Study of Healthcare Workers Before, During and After Vaccination.

The impact of coronavirus disease 2019 vaccination on viral characteristics of breakthrough infections is unknown. In this prospective cohort study, incidence of severe acute respiratory syndrome coronavirus 2 infection decreased following vaccination. Although asymptomatic positive tests were observed following vaccination, the higher cycle thresholds, repeat negative tests, and inability to culture virus raise questions about their clinical significance.

Who's slipping through the cracks? A comprehensive individual, clinical and health system characterization of people with virological failure on first-line HIV treatment in Uganda and South Africa.

OBJECTIVES: HIV virological failure remains a major threat to programme success in sub-Saharan Africa. While HIV drug resistance (HIVDR) and inadequate adherence are the main drivers of virological failure, the individual, clinical and health system characteristics that lead to poor outcomes are not well understood. The objective of this paper is to identify those characteristics among people failing first-line antiretroviral therapy (ART). METHODS: We enrolled a cohort of adults in HIV care experiencing virological failure on first-line ART at five sites and used standard statistical methods to characterize them with a focus on three domains: individual/demographic, clinical, and health system, and compared each by country of enrolment. RESULTS: Of 840 participants, 51% were women, the median duration on ART was 3.2 years [interquartile range (IQR) 1.1, 6.4 years] and the median CD4 cell count prior to failure was 281 cells/µL (IQR 121, 457 cells/µL). More than half of participants [53%; 95% confidence interval (CI) 49-56%] stated that they had > 90% adherence and 75% (95% CI 72-77%) took their ART on time all or most of the time. Conversely, the vast majority (90%; 95% CI 86-92%) with a completed genotypic drug resistance test had any HIV drug resistance. This population had high health system use, reporting a median of 3 (IQR 2.6) health care visits and a median of 1 (IQR 1.1) hospitalization in the preceding 6 months. CONCLUSIONS: Patients failing first-line ART in sub-Saharan Africa generally report high rates of adherence to ART, have extremely high rates of HIV drug resistance and utilize significant health care resources. Health systems interventions to promptly detect and manage treatment failure will be a prerequisite to establishing control of the HIV epidemic.

Duration of viral shedding and culture positivity with postvaccination SARS-CoV-2 delta variant infections.

Isolation guidelines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are largely derived from data collected prior to the emergence of the delta variant. We followed a cohort of ambulatory patients with postvaccination breakthrough SARS-CoV-2 infections with longitudinal collection of nasal swabs for SARS-CoV-2 viral load quantification, whole-genome sequencing, and viral culture. All delta variant infections in our cohort were symptomatic, compared with 64% of non-delta variant infections. Symptomatic delta variant breakthrough infections were characterized by higher initial viral load, longer duration of virologic shedding by PCR, greater likelihood of replication-competent virus at early stages of infection, and longer duration of culturable virus compared with non-delta variants. The duration of time since vaccination was also correlated with both duration of PCR positivity and duration of detection of replication-competent virus. Nonetheless, no individuals with symptomatic delta variant infections had replication-competent virus by day 10 after symptom onset or 24 hours after resolution of symptoms. These data support US CDC isolation guidelines as of November 2021, which recommend isolation for 10 days or until symptom resolution and reinforce the importance of prompt testing and isolation among symptomatic individuals with delta breakthrough infections. Additional data are needed to evaluate these relationships among asymptomatic and more severe delta variant breakthrough infections.

Increasing Men's Engagement in HIV Testing and Treatment Programs Through Crowdsourcing: A Mixed-Methods Analysis in Eswatini.

BACKGROUND: Sub-Saharan African HIV programs have had limited success in engaging men. Crowdsourcing contests may be a useful method to spur men's engagement in HIV services. We evaluated contributions and social media response to a crowdsourcing contest focused on increasing men's engagement in Eswatini HIV services. METHODS: We conducted a crowdsourcing contest to gain insight from the public on how HIV campaigns can more effectively engage young (20-40 years old) men in HIV services. Eligible submissions included images, songs, videos, and Internet memes. We used standard qualitative methods to examine textual themes from submissions. We examined social media response using Facebook analytics, comparing the number of people reached through crowdsourced HIV messages and the number of people reached through conventional HIV messages. RESULTS: We received 144 submissions from 83 participants. They represented 55 towns and all 4 regions of Eswatini. The contest page gained 461 followers on Facebook. Emergent themes included appealing to men's roles as protectors by suggesting that they need to take care of their own health to continue safeguarding their families. Crowdsourced messages reached a mean of 88 individuals across 4 posts; conventional messages reached a mean of 75 individuals across 4 posts. CONCLUSIONS: Crowdsourcing contest submissions provided insight on how to encourage men to engage in Eswatini HIV services. Crowdsourcing contests can be effective in collecting messages from men to create more locally relevant communication materials for HIV programs.

Coronavirus Disease 2019 (COVID-19) Transmission in the United States Before Versus After Relaxation of Statewide Social Distancing Measures.

BACKGROUND: Weeks after issuing social distancing orders to suppress severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and reduce growth in cases of severe coronavirus disease 2019 (COVID-19), all US states and the District of Columbia partially or fully relaxed these measures. METHODS: We identified all statewide social distancing measures that were implemented and/or relaxed in the United States between 10 March and 15 July 2020, triangulating data from state government and third-party sources. Using segmented linear regression, we estimated the extent to which relaxation of social distancing affected epidemic control, as indicated by the time-varying, state-specific effective reproduction number (Rt). RESULTS: In the 8 weeks prior to relaxation, mean Rt declined by 0.012 units per day (95% confidence interval [CI], -.013 to -.012), and 46/51 jurisdictions achieved Rt < 1.0 by the date of relaxation. After relaxation of social distancing, Rt reversed course and began increasing by 0.007 units per day (95% CI, .006-.007), reaching a mean Rt of 1.16. Eight weeks later, the mean Rt was 1.16 and only 9/51 jurisdictions were maintaining an Rt < 1.0. Parallel models showed similar reversals in the growth of COVID-19 cases and deaths. Indicators often used to motivate relaxation at the time of relaxation (eg, test positivity rate <5%) predicted greater postrelaxation epidemic growth. CONCLUSIONS: We detected an immediate and significant reversal in SARS-CoV-2 epidemic suppression after relaxation of social distancing measures across the United States. Premature relaxation of social distancing measures undermined the country's ability to control the disease burden associated with COVID-19.