The Impact of COVID-19 on the HIV Care Continuum in a Large Urban Southern Clinic.

Access to care is essential for people with HIV (PWH) but may have been affected during the COVID-19 pandemic. We conducted a retrospective cross-sectional study of adult PWH receiving care in a large southeastern comprehensive care clinic in the United States. Patients in care between January 1, 2017, and July 30, 2020, were included. Race/ethnicity, sex, HIV-1 RNA, CD4 + lymphocyte count were included as baseline covariates. Outcomes included clinic attendance, receipt of HIV-1 RNA PCR testing, and virologic suppression (HIV-1 RNA < 200 copies/mL); outpatient encounters included new patient encounters, follow-up visits, and mental health encounters. Total medical encounters, including telemedicine, decreased by 827 visits (33%) when comparing the second quarters of 2019 and 2020. New patient encounters decreased by 23.5% from 81 to 62 during this period. The second quarter of 2020 saw the lowest number of new patient visits since 2017. HIV-1 RNA testing and the proportion of patients with virologic suppression decreased during the pandemic (p < 0.001 for both). Total mental health encounters, on the other hand, increased by 14% during April-June 2020 compared to April-June 2019. Mental health electronic communications increased by 60% from 312 to 500 during the same period, with a 20% increase in medication refills. The COVID-19 pandemic affected outpatient visits, viral load surveillance, and virologic suppression but led to an increase in mental health encounters in a comprehensive care clinic setting.

The relationship between adverse neighborhood socioeconomic context and HIV continuum of care outcomes in a diverse HIV clinic cohort in the Southern United States.

Retention in care and viral suppression are critical to delaying HIV progression and reducing transmission. Neighborhood socioeconomic context (NSEC) may affect HIV care receipt. We therefore assessed NSEC's impact on retention and viral suppression in a diverse HIV clinical cohort. HIV-positive adults with ≥1 visit at the Vanderbilt Comprehensive Care Clinic and 5-digit ZIP code tabulation area (ZCTA) information between 2008 and 2012 contributed. NSEC z-score indices used neighborhood-level socioeconomic indicators for poverty, education, labor-force participation, proportion of males, median age, and proportion of residents of black race by ZCTA. Retention was defined as ≥2 HIV care visits per calendar year, >90 days apart. Viral suppression was defined as an HIV-1 RNA <200 copies/mL at last measurement per calendar year. Modified Poisson regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI). Among 2272 and 2541 adults included for retention and viral suppression analyses, respectively, median age and CD4 count at enrollment were approximately 38 (1st and 3rd quartile: 30, 44) years and 351 (176, 540) cells/µL, respectively, while 24% were female, and 39% were black. Across 243 ZCTAs, median NSEC z-score was 0.09 (-0.66, 0.48). Overall, 79% of person-time contributed was retained and 74% was virally suppressed. In adjusted models, NSEC was not associated with retention, though being in the 4th vs. 1st NSEC quartile was associated with lack of viral suppression (RR = 0.88; 95% CI: 0.80-0.97). Residing in the most adverse NSEC was associated with lack of viral suppression. Future studies are needed to confirm this finding.

Active cocaine use is associated with lack of HIV-1 virologic suppression independent of nonadherence to antiretroviral therapy: use of a rapid screening tool during routine clinic visits.

Clarifying the relationship between illicit drug use and HIV-1 virologic suppression requires characterization of both illicit drug use activity and adherence to antiretroviral therapy (ART). We developed a rapid clinical questionnaire to assess prior 7-day illicit drug use and ART adherence in a cross-sectional study among 1777 HIV-infected persons in care. Of these, 76% were male, 35% were African-American, and 8% reported injection drug use as their probable route of HIV-1 infection. Questionnaire-reported frequencies of cocaine and marijuana use within the previous 7 days were 3.3% and 12.1%, respectively. Over three quarters (77.8%) of participants were on ART, of whom 69.7% had HIV-1 virologic suppression (HIV-1 RNA<48 copies/mL). Univariate analyses revealed that compared to no use, cocaine and marijuana use were both associated with missed ART doses (P<0.01). Multivariable logistic regression analysis adjusting for nonadherence demonstrated that cocaine use was independently associated with failing to achieve virologic suppression (adjusted odds ratio (aOR): 0.46; 95% confidence interval (95% CI): 0.22-0.98) but marijuana use was not (aOR: 1.08; 95% CI: 0.72-1.62). This result strengthens the evidence of a direct effect of cocaine on virologic control, independent of nonadherence to ART.

Sex and Race Disparities in Mortality and Years of Potential Life Lost Among People With HIV: A 21-Year Observational Cohort Study.

Background: Since the availability of antiretroviral therapy, mortality rates among people with HIV (PWH) have decreased; however, this does not quantify premature deaths among PWH, and disparities persist. Methods: We examined all-cause and premature mortality among PWH receiving care at the Vanderbilt Comprehensive Care Clinic from January 1998 to December 2018. Mortality rates were compared by demographic and clinical factors, and adjusted incidence rate ratios (aIRRs) were calculated using multivariable Poisson regression. For individuals who died, age-adjusted years of potential life lost (aYPLL) per total person-years living with HIV were calculated from US sex-specific life tables, and sex and race differences were examined using multivariable linear regression. Results: Among 6531 individuals (51% non-Hispanic [NH] White race, 40% NH Black race, 21% cis-gender women, 78% cis-gender men) included, 956 (14.6%) died. In adjusted analysis, PWH alive in the most recent calendar era (2014-2018) had decreased risk of mortality compared with those in the earliest calendar era (1998-2003; aIRR, 0.22; 95% CI, 0.17-0.29), and women had increased risk of death compared with men (aIRR, 1.31; 95% CI, 1.12-1.54). Of those who died, Black women had the highest aYPLL (aIRR, 592.5; 95% CI, 588.4-596.6), followed by Black men (aIRR, 470.7; 95% CI, 468.4-472.9), White women (aIRR, 411.5; 95% CI, 405.6-417.4), then White men (aIRR, 308.6; 95% CI, 308.0-309.2). In adjusted models, higher YPLL remained associated with NH Black race and cis-gender women, regardless of HIV risk factor. Conclusions: Despite marked improvement over time, sex disparities in mortality as well as sex and race disparities in YPLL remained among PWH in this cohort.

Visualizing the Geography of HIV Observational Cohorts With Density-Adjusted Cartograms.

BACKGROUND: Maps are potent tools for describing the spatial distribution of population and disease characteristics and, thereby, for appropriately targeting public health interventions. People with HIV (PWH) tend to live in densely populated and spatially compact areas that may be difficult to visualize on maps using unadjusted geographic or political borders. SETTING: To illustrate these challenges, we used geographic data from adult PWH at the Vanderbilt Comprehensive Care Clinic (VCCC) in Nashville, Tennessee, and aggregated data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) from 1998 to 2015. METHODS: We compared choropleth maps that use differential shading of political/geographic boundaries with density-adjusted cartograms that allow for shading and deformed boundaries according to a variable of interest, such as PWH. RESULTS: Cartograms enlarged high-burden areas and shrank low-burden areas of PWH, improving visual interpretation of where to focus HIV prevention and mitigation efforts, when compared with choropleth maps. Cartograms may also demonstrate cohort representativeness of underlying populations (eg, Tennessee for VCCC or the United States for NA-ACCORD), which can guide efforts to assess external validity and improve generalizability. CONCLUSION: Choropleth maps and cartograms offer powerful visual evidence of the geographic distribution of HIV disease and cohort representation and should be used to guide targeted public health interventions.

Increased detectability of plasma HIV-1 RNA after introduction of a new assay and altered specimen-processing procedures.

After changes to assay and specimen-processing methods, plasma human immunodeficiency virus type 1 (HIV-1) RNA was frequently detectable in patients who previously had well-suppressed HIV-1 RNA levels. This artifact is attributable to shipping frozen plasma in primary plasma preparation tubes and is not caused by the HIV-1 RNA detection assay; it can be avoided by shipping plasma in a secondary tube.

Risk Prediction Tool for Medical Appointment Attendance Among HIV-Infected Persons with Unsuppressed Viremia.

Successful treatment of HIV infection requires regular clinical follow-up. A previously published risk-prediction tool (RPT) utilizing data from the electronic health record (EHR) including medication adherence, previous appointment attendance, substance abuse, recent CD4+ count, prior antiretroviral therapy (ART) exposure, prior treatment failure, and recent HIV-1 viral load (VL) has been shown to predict virologic failure at 1 year. If this same tool could be used to predict the more immediate event of appointment attendance, high-risk patients could be identified and interventions could be targeted to improve this outcome. We conducted an observational cohort study at the Vanderbilt Comprehensive Care Clinic from August 2013 through March 2014. Patients with routine medical appointments and most recent HIV-1 VL >200 copies/mL were included. Risk scores for a modified RPT were calculated based on data from the EHR. Odds ratios (OR) for missing the next appointment were estimated using multivariable logistic regression. Among 510 persons included, median age was 39 years, 74% were male, 55% were black, median CD4+ count was 327 cells/mm(3) [Interquartile Range (IQR): 142-560], and median HIV-1 VL was 21,818 copies/mL (IQR: 2,030-69,597). Medium [OR 3.95, 95% confidence interval (CI) 2.08-7.50, p-value<0.01] and high (OR 9.55, 95% CI 4.31-21.16, p-value<0.01) vs. low RPT risk scores were independently associated with missing the next appointment. RPT scores, constructed using readily available data, allow for risk-stratification of HIV medical appointment non-attendance and could support targeting limited resources to improve appointment adherence in groups most at-risk of poor HIV outcomes.

Tenofovir (TDF)-selected or abacavir (ABC)-selected low-frequency HIV type 1 subpopulations during failure with persistent viremia as detected by ultradeep pyrosequencing.

Detection of drug resistance is critical for determining antiretroviral treatment options. Ultradeep pyrosequencing (UDPS; 454 Life Sciences) is capable of detecting virus variant subpopulations with much greater sensitivity than population sequencing, which typically has a detection limit around 20%. UDPS of the HIV-1 reverse transcriptase (RT) (amino acids 56-120) was performed to detect the key mutations K65R and L74V associated with tenofovir and abacavir use. Plasma specimens from subjects with persistent rebound viremia following suppression on tenofovir (n = 8) or abacavir (n = 9)-based therapy were studied. Samples from a subject treated with zidovudine/lamivudine/efavirenz with a similar loss of virologic response served as a control. HIV-1 plasma RNA was ≥3.68 log(10) copies/ml at all time points sequenced. The median number of UDPS sequences analyzed/time point was 33,246. Among the eight tenofovir-treated subjects, three showed high-frequency (>20%) RT K65R at the time of failure, whereas one showed low-frequency (<20%) L74V; no low-frequency K65R was detected in these subjects. Among the nine abacavir-treated subjects, three showed low-frequency K65R; no L74V was detected in these patients. No K65R or L74V was detected in the samples from the control subject. At failure, other RT mutations were detected, including low-frequency NNRTI-resistant species detected at ≥1 time point in nine subjects; the key NNRTI mutation K103N, however, was always observed at >20% frequency. Although UDPS is useful in the detection of low-frequency subpopulations with transmitted resistance in antiviral-naive patients, it may have less utility in treatment-experienced patients with persistent viremia on therapy.

Race and sex differences in antiretroviral therapy use and mortality among HIV-infected persons in care.

BACKGROUND: There are conflicting data regarding race, sex, and mortality among persons infected with human immunodeficiency virus (HIV). We studied all-cause mortality among persons in care during the highly-active antiretroviral therapy (HAART) era. METHODS: This retrospective cohort study included patients who made>or=1 clinic visit from January 1998 through December 2005. RESULTS: Of 2605 patients (with 6657 person-years of follow-up), 38% were black and 24% were female. The percentage of time in care while receiving HAART was lower for blacks than for nonblacks (47% vs. 76%; P<.001) and for females than for males (57% vs. 71%; P=.01). There were 253 deaths (38 per 1000 person-years). After adjustment for characteristics at baseline, death was associated with black race (hazard ratio [HR], 1.33; P .04), female sex (HR, 1.53; P .007), injection drug use (IDU) as a risk factor for HIV infection (HR, 1.61; P .009), older age (HR, 1.45 per 10 years; P<.001), a lower CD4 cell count (HR, 0.59 for 200 vs. 350 cells/mm3; P<.001) and a higher HIV type 1 RNA level (HR, 1.35; P<.001). After adjustment for the length of time that HAART was received, black race (HR, 1.00; P .99) and IDU (HR, 1.37; P .09) were no longer associated with death, but female sex was (HR, 1.62; P=.002). CONCLUSIONS: Race-associated differences in mortality likely resulted from HAART use. Women had an increased risk of death even after adjustment for HAART use. Addressing racial disparities will require improved HAART utilization. Increased mortality among women requires further study.

Pregnancy and HIV disease progression during the era of highly active antiretroviral therapy.

BACKGROUND: Before the availability of highly active antiretroviral therapy (HAART), there was no clear effect of pregnancy on human immunodeficiency virus (HIV) disease progression. This has not been assessed during the HAART era. METHODS: We conducted an observational cohort study among HIV-infected women with >or=1 outpatient clinic visit between January 1997 and December 2004. HIV disease progression was defined as the occurrence of an AIDS-defining event or death. RESULTS: Of 759 women who met the inclusion criteria, 139 (18%) had had >1 pregnancy, and 540 (71%) had received HAART. There was no difference in HAART duration by pregnancy status. Eleven pregnant (8%) and 149 nonpregnant (24%) women progressed to AIDS or death. After controlling for age, baseline CD4(+) lymphocyte count, baseline HIV-1 RNA level, and durable virologic suppression in a Cox proportional hazards model that included propensity score for pregnancy, pregnancy was associated with a decreased risk of disease progression (hazard ratio [HR], 0.40 [95% confidence interval {CI}, 0.20-0.79]; P=.009]). In a matched-pair analysis of 81 pregnant women matched to 81 nonpregnant women according to age, baseline CD4(+) lymphocyte count, receipt of HAART, and date of cohort entry, pregnant women had a lower risk of disease progression both before (HR, 0.10 [95% CI, 0.01-0.89]; P=.04) and after (HR, 0.44 [95% CI, 0.19-1.00]; P=.05) the pregnancy event. CONCLUSION: Pregnancy was associated with a lower risk of HIV disease progression in this HAART-era study. This finding could be the result of the healthier immune status of women who become pregnant or could possibly be related to a beneficial interaction between pregnancy and HAART.

CD4 lymphocyte percentage predicts disease progression in HIV-infected patients initiating highly active antiretroviral therapy with CD4 lymphocyte counts >350 lymphocytes/mm3.

BACKGROUND: The optimal timing of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients with > or = 200 absolute CD4 lymphocytes/mm3 is unknown. CD4 lymphocyte percentage could add prognostic information. METHODS: Persons who initiated HAART between 1 January 1998 and 1 January 2003, received > or = 30 days of therapy, and had baseline CD4 lymphocyte data available were included in the study. The log-rank test for time to event and Cox proportional hazards models were used to determine predictors of a new acquired immunodeficiency syndrome-defining illness or death. RESULTS: A total of 788 patients met the inclusion criteria. At baseline, subjects had a median of 225 CD4 lymphocytes/mm3 and 17% CD4 lymphocytes. Subjects with < 17% CD4 lymphocytes had earlier disease progression, compared with subjects with > or = 17%, both in the entire cohort (P<.0001) and of those subjects with > 350 absolute CD4 lymphocytes/mm3 at baseline (P=.03). CD4 lymphocyte percentage < 17% was the strongest predictor of disease progression among subjects in this latter group (hazard ratio, 3.57; P=.045). CONCLUSIONS: In this cohort, CD4 lymphocyte percentage predicted disease progression in HIV-infected subjects who initiated therapy with > 350 CD4 lymphocytes/mm3. This information may help identify persons who will derive the greatest benefit from initiation of HAART.