An exploratory study to characterize the HIV testing-to-care continuum to improve outcomes for Black and Latinx residents of South Los Angeles.

BACKGROUND: South Los Angeles (SPA6), with mostly Black (27.4%) and Latinx (68.2%) residents, has the second highest rates of new HIV diagnoses (31 per 100,000) in Los Angeles County. However, there is limited understanding of the HIV testing-to-care continuum among newly diagnosed in this setting. METHODS: We conducted an exploratory study that analyzed de-identified data, including demographic characteristics and biomedical outcomes, from the electronic medical records of individuals newly diagnosed with HIV from 2016-2020 at the only public safety-net, county-run health department HIV clinic in SPA 6. We used Pearson Chi-square and Fisher's Exact test to explore associations with HIV outcomes and a Kaplan-Meier survival curve to assess the time to linkage to care. RESULTS: A total of 281 patients were identified. The majority (74.1%) presented with a baseline CD4 <500, many of which presented with a CD4<200 (39.2%). We found twice as many newly diagnosed Black individuals in our study population (48.2%) when compared to LAC (23%), despite only accounting for 27.4% of residents in SPA 6. The majority were linked to care within 30 days of positive test and prescribed anti-retroviral therapy. Viral suppression (59.8%) and undetectable VL (52.6%) were achieved within the year following diagnosis, with 9.3% lost to follow-up. Of those who became virally suppressed, 20.7% experienced viral rebound within the year following diagnosis. CONCLUSION: The large proportion of patients with a baseline CD4 <500 raises concerns about late diagnoses. Despite high rates of linkage to care and ART prescription, achievement of sustained viral suppression remains low with high rates of viral rebound. Longitudinal studies are needed to understand the barriers to early testing, retention in care, and treatment adherence to develop strategies and interventions with community organizations that respond to the unique needs of people living with HIV in South Los Angeles.

Unmet Needs Among Out of Care and Recently Diagnosed Women of Color With HIV: Opportunities for Focused Interventions.

OBJECTIVE: Women of color (WoC) have lower retention in care and higher HIV/AIDS-related morbidity, compared with other populations. Barriers to care include lack of family support, inadequate HIV/AIDS services, and stigma, and women may face greater unmet needs for services including housing and employment. This descriptive study explores the unmet needs of WoC participating in the Health Resources and Services Administration's Special Projects of National Significance (SPNS) Program, Dissemination of Evidence Informed Interventions (HRSA/SPNS DEII) Initiative. SETTING: Six urban health clinics across the United States. PARTICIPANTS: Eligible participants were cis- or transgender women who were newly diagnosed with HIV/AIDS in the past 12 months, out of care for at least 6 months, or not virally suppressed. Participants enrolled from November 2016 to November 2018. MAIN OUTCOMES: Our primary outcome of interest was unmet needs at enrollment for 6 core services: housing, transportation, benefits, mental health or substance use treatment, medication assistance, and medical care. We examined differences in unmet needs stratified by participant characteristics and used multivariate regression to identify the social and health risk factors associated with higher unmet needs. RESULTS: Among the 529 WoC, the most frequently reported expressed needs were transportation (50.1%), housing (41.2%), benefits (28.2%), medication assistance (24.5%), and substance use or mental health treatment (24.3%). Participants with a significantly higher number of overall unmet needs included those who were older (40 years or older), were unstably housed, had a history of incarceration, identified as a transgender woman, were US born, had no caregiver responsibilities, and did not have a case manager at enrollment. CONCLUSIONS: Our findings indicate the importance of screening for and developing focused strategies to address the unmet needs for WoC if viral suppression is to be achieved.

Implementation and Operational Research: The Navigation Program: An Intervention to Reengage Lost Patients at 7 HIV Clinics in Los Angeles County, 2012-2014.

The Navigation Program is a health department-community agency collaboration to reengage lost HIV clinic patients in Los Angeles County using best practices from disease investigator services locator activities and the Antiretroviral Treatment Access Study (ARTAS), a CDC-recommended intervention. Clinic databases were reviewed to identify HIV patients who: (1) had no HIV care visits in 6-12 months and last viral load was greater than 200 copies per milliliter; (2) had no HIV care visits in >12 months; (3) were newly diagnosed and never in care; or (4) were recently released from jail/prison/other institution with no regular HIV medical provider. Patients were contacted by trained Navigators using locator information from clinic medical records, HIV/sexually transmitted disease surveillance, and people-finder databases and offered enrollment in a modified ARTAS intervention. Among the 1139 lost clinic patients identified, 36% were in care elsewhere, 29% could not be located, 8% returned to the clinic independently, 4% declined enrollment, and 7% (n = 78) were located and enrolled in the intervention. Participants received an average of 4.5 Navigator sessions over 11.6 hours. Among reengaged patients, 68% linked within 3 months, 85% linked within 6 months, and 94% linked within 12 months, and 82% of linked patients were retained in care 12 months after study enrollment. The percentage of linked patients virally suppressed was compared at time of linkage by the Navigators (52%) with a second viral load measure after linkage to care (63%) (χ(2) = 11.8; P = 0.01). The combined disease investigator services/ARTAS model of reengagement was effective for locating and reengaging lost HIV clinic patients. Access to HIV surveillance data is critical for the efficient identification of persons truly in need of reengagement.

Systemic Immune Activation and HIV Shedding in the Female Genital Tract.

BACKGROUND: Plasma HIV RNA is the most significant determinant of cervical HIV shedding. However, shedding is also associated with sexually transmitted infections (STIs) and cervical inflammation. The mechanism by which this occurs is poorly understood. There is evidence that systemic immune activation promotes viral entry, replication, and HIV disease progression. We hypothesized that systemic immune activation would be associated with an increase in HIV genital shedding. METHODS: Clinical assessments, HIV RNA in plasma and genital secretions, and markers of immune activation (CD38(+)DR(+) and CD38(-)DR(-)) on CD4(+) and CD8(+) T cells in blood were evaluated in 226 HIV+ women enrolled in the Women's Interagency HIV Study. There were 569 genital evaluations of which 159 (28%) exhibited HIV RNA shedding, defined as HIV viral load >80 copies per milliliter. We tested associations between immune activation and shedding using generalized estimating equations with logit link function. RESULTS: In the univariate model, higher levels of CD4(+) and CD8(+) T-cell activation in blood were significantly associated with genital tract shedding. However, in the multivariate model adjusting for plasma HIV RNA, STIs, and genital tract infections, only higher levels of resting CD8(+) T cells (CD38(-)DR(-)) were significantly inversely associated with HIV shedding in the genital tract (odds ratios = 0.44, 95% confidence interval: 0.21 to 0.9, P = 0.02). CONCLUSIONS: The association of systemic immune activation with genital HIV shedding is multifactorial. Systemic T-cell activation is associated with genital tract shedding in univariate analysis but not when adjusting for plasma HIV RNA, STIs, and genital tract infections. In addition, women with high percentage of resting T cells are less likely to have HIV shedding compared with those with lower percentages. These findings suggest that a higher percentage of resting cells, as a result of maximal viral suppression with treatment, may decrease local genital activation, HIV shedding, and transmission.

The effect of prenatal highly active antiretroviral therapy on the transmission of congenital and perinatal/early postnatal cytomegalovirus among HIV-infected and HIV-exposed infants.

BACKGROUND: Before highly active antiretroviral therapy (HAART), congenital cytomegalovirus (CMV) rates were higher among human immunodeficiency virus (HIV)-exposed infants than unexposed infants. This study examines congenital and perinatal/early postnatal (P/EP) CMV among HIV-exposed infants pre- and post- HAART. METHODS: Infants born to HIV-infected women were evaluated for congenital CMV (CMV-positive culture in first 3 weeks of life) and P/EP CMV (positive culture in first 6 months of life). Prenatal maternal HAART was defined as triple antiretroviral therapy (ART) with at least 1 nonnucleoside reverse-transcriptase inhibitor or protease inhibitor. RESULTS: Among 414 infants evaluated, 1678 CMV assessment days were completed (mean = 3 assessment days per infant). Congenital CMV rates did not differ by time period, HAART use, or infant HIV infection status. P/EP CMV rates were greater for the 1988-1996 birth cohort (17.9%) compared with the 1997-2002 birth cohort (8.9%) (P < .01), HIV-infected versus uninfected infants (P < .01), and infants with no maternal ART versus those with ART (P < .01). Controlling for potential confounders, P/EP CMV was associated with no maternal ART (odds ratio = 4.7; P < .01), and among those with no maternal ART, P/EP CMV was associated with maternal CD4 count ≤200 cells/µL (P < .01). For HIV-uninfected infants with P/EP CMV, symptoms including splenomegaly, lymphadenopathy, and hepatomegaly were associated with no maternal HAART versus those with HAART (41% vs 6%; P < .05). CONCLUSIONS: Although congenital CMV rates did not change, the post-HAART era showed reduced P/EP CMV and occurrence of related clinical symptoms. These findings underscore the importance of prenatal HAART for all HIV-infected pregnant women.

Permissive and protective factors associated with presence, level, and longitudinal pattern of cervicovaginal HIV shedding.

BACKGROUND: Cervicovaginal HIV level (CV-VL) influences HIV transmission. Plasma viral load (PVL) correlates with CV-VL, but discordance is frequent. We evaluated how PVL, behavioral, immunological, and local factors/conditions individually and collectively correlate with CV-VL. METHODS: CV-VL was measured in the cervicovaginal lavage fluid (CVL) of 481 HIV-infected women over 976 person-visits in a longitudinal cohort study. We correlated identified factors with CV-VL at individual person-visits and detectable/undetectable PVL strata by univariate and multivariate linear regression and with shedding pattern (never, intermittent, persistent ≥3 shedding visits) in 136 women with ≥3 visits by ordinal logistic regression. RESULTS: Of 959 person-visits, 450 (46.9%) with available PVL were discordant, 435 (45.3%) had detectable PVL with undetectable CV-VL, and 15 (1.6%) had undetectable PVL with detectable CV-VL. Lower CV-VL correlated with highly active antiretroviral therapy (HAART) usage (P = 0.01). Higher CV-VL correlated with higher PVL (P < 0.001), inflammation-associated cellular changes (P = 0.03), cervical ectopy (P = 0.009), exudate (P = 0.005), and trichomoniasis (P = 0.03). In multivariate analysis of the PVL-detectable stratum, increased CV-VL correlated with the same factors and friability (P = 0.05), while with undetectable PVL, decreased CV-VL correlated with HAART use (P = 0.04). In longitudinal analysis, never (40.4%) and intermittent (44.9%) shedding were most frequent. Higher frequency shedders were more likely to have higher initial PVL [odds ratio (OR) = 2.47/log10 increase], herpes simplex virus type 2 seropositivity (OR = 3.21), and alcohol use (OR = 2.20). CONCLUSIONS: Although PVL correlates strongly with CV-VL, discordance is frequent. When PVL is detectable, cervicovaginal inflammatory conditions correlate with increased shedding. However, genital shedding is sporadic and not reliably predicted by associated factors. HAART, by reducing PVL, is the most reliable means of reducing cervicovaginal shedding.

Itraconazole treatment of nonmeningeal coccidioidomycosis in children: two case reports and review of the literature.

Coccidioides immitis causes a wide range of disease in humans. Fluconazole and itraconazole are effective treatments. Clinical evidence suggests that itraconazole is equivalent or superior to fluconazole in treating osteoarticular infections in rates of cure and recurrence. We report 2 cases of coccidioidomycosis involving bone in children successfully treated with itraconazole oral solution. Itraconazole oral solution is effective in treating nonmeningeal coccidioidomycosis in children, particularly skeletal disease, and infections that are refractory to fluconazole.

Correlates of perinatal depression in HIV-infected women.

Maternal perinatal depression (PND) may interfere with effective perinatal HIV care. In order to begin examining the prevalence and characteristics of PND in HIV-infected women, we analyzed data from the medical records of all HIV-infected women who had received perinatal care in the Maternal-Child and Adolescent Center for Infectious Diseases and Virology at LAC/USC Medical Center from 1997 through 2006. Data from 273 individual women (328 live births) were analyzed. Demographic, medical history, psychosocial, pregnancy related, and HIV-related factors measured during the perinatal period were examined for an association with PND using multivariate logistic regression with generalized estimating equations to account for the within subject correlation due to multiple births per mother. The overall prevalence of PND was 30.8%. Multivariate analysis showed that PND was significantly associated with substance abuse during pregnancy (odds ratio [OR] = 2.81, 95% confidence interval [CI]: 1.35-5.82) and past history of psychiatric illness (OR = 3.72, 95% CI: 2.06-6.71). Compared to mothers with CD4 nadir greater than 500 cells/mm3, mothers with a CD4 nadir during pregnancy #200 cells=mm3 were 3.1 times more likely to experience PND (OR = 3.01, 95% CI: 1.32-6.88). Women who had antiretroviral (ARV) medications adherence problems during pregnancy were more likely to experience PND than women who were adherent (OR = 2.14, 95% CI: 1.08-4.23). These preliminary results suggest that rates of PND among HIV-infected women are substantial. We conclude that pregnant HIV-infected women should be routinely screened for PND. Prospective studies examining the bio-psycho-social markers of PND in HIV-infected women are indicated.

Epidemiology of Pneumocystis colonization in families.

Whether Pneumocystis colonization is transmitted in families with human immunodeficiency virus (HIV)-infected members is unknown. Using nested polymerase chain reaction of oropharyngeal or nasopharyngeal samples, we detected colonization in 11.4% of HIV-infected adults and in 3.3% of their children, but there was no evidence of clustering.

Factors associated with hepatitis C viremia in a large cohort of HIV-infected and -uninfected women.

BACKGROUND: Co-infection with hepatitis C virus (HCV) is common among HIV-infected women. OBJECTIVE: To further our understanding of the risk factors for HCV viremia and the predictors of HCV viral load among women. STUDY DESIGN: We investigated sociodemographic, immunologic, and virologic factors associated with presence and level of HCV viremia among 1049 HCV-seropositive women, 882 of whom were HIV-infected and 167 HIV-uninfected at their entry into the Women's Interagency HIV Study. RESULTS: Plasma HCV RNA was detected in 852 (81%) of these 1049 women (range: 1.2-7.8 log(10)copies/ml). HCV-viremic women were more likely to have an HIV RNA level >100,000 copies/ml (P=0.0004), to have reported smoking (P=0.01), or to be Black (P=0.005). They were less likely to have current or resolved hepatitis B infection. HCV RNA levels were higher in women who were >35 years old, or HIV-infected. Current smoking and history of drug use (crack/freebase cocaine, marijuana, amphetamines, or heroin) were each associated with both presence and level of viremia. CONCLUSIONS: Substance abuse counseling aimed at eliminating ongoing use of illicit drugs and tobacco may reduce clinical progression, improve response to treatment, and decrease HCV transmission by lowering levels of HCV viremia in women.

An epidemiological investigation of a sustained high rate of pediatric parapneumonic empyema: risk factors and microbiological associations.

We investigated the increasing incidence of pediatric empyema during the 1990s at Primary Children's Medical Center in Salt Lake City. Of 540 children hospitalized with community-acquired bacterial pneumonia (CAP) who were discharged from 1 July 1993 through 1 July 1999, 153 (28.3%) had empyema. The annual population incidence of empyema increased during the study period from 1 to 5 cases per 100,000 population aged <19 years. Streptococcus pneumoniae was identified as the most common cause of CAP with or without empyema; serotype 1 accounted for 50% of the cases of pneumococcal empyema. Patients with empyema were more likely to be >3 years old, to have > or =7 days of fever, to have varicella, and to have received antibiotics and ibuprofen before admission to the hospital, compared with patients without empyema (P<.0001 for each factor). The increasing incidence of empyema was associated with infection due to S. pneumoniae serotype 1, outpatient treatment with certain antibiotics, ibuprofen use, and varicella.