High prevalence of pre-treatment HIV drug resistance in Papua New Guinea: findings from the first nationally representative pre-treatment HIV drug resistance study.

BACKGROUND: Determining the prevalence of pre-treatment HIV drug resistance (PDR) is important to assess the effectiveness of first-line therapies. To determine PDR prevalence in Papua New Guinea (PNG), we conducted a nationally representative survey. METHODS: We used a two-stage cluster sampling method to recruit HIV treatment initiators with and without prior exposure to antiretroviral therapies (ART) in selected clinics. Dried blood spots were collected and tested for PDR. RESULTS: A total of 315 sequences were available for analysis. The overall PDR prevalence rate was 18.4% (95% CI 13.8-24.3%). The prevalence of PDR to non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs) was 17.8% (95% CI 13.6-23.0%) and of PDR to nucleoside reverse transcriptase inhibitors (NRTIs) was 6.3% (95% CI 1.6-17.1%). The PDR prevalence rate among people reinitiating ART was 42.4% (95% CI 29.1-56.4%). CONCLUSIONS: PNG has a high PDR prevalence rate, especially to NNRTI-based first-line therapies. Our findings suggest that removing NNRTIs as part of first-line treatment is warranted and will lead to improving viral suppression rates in PNG.

Coronavirus Disease 2019 (COVID-19) Prevalences Among People Experiencing Homelessness and Homelessness Service Staff During Early Community Transmission in Atlanta, Georgia, April-May 2020.

BACKGROUND: In response to reported coronavirus disease 2019 (COVID-19) outbreaks among people experiencing homelessness (PEH) in other US cities, we conducted multiple, proactive, facility-wide testing events for PEH living sheltered and unsheltered and homelessness service staff in Atlanta, Georgia. We describe the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence and associated symptoms, and review shelter infection prevention and control (IPC) policies. METHODS: PEH and staff were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) during 7 April-6 May 2020. A subset of PEH and staff was screened for symptoms. Shelter assessments were conducted concurrently at a convenience sample of shelters using a standardized questionnaire. RESULTS: Overall, 2875 individuals at 24 shelters and 9 unsheltered outreach events underwent SARS-CoV-2 testing, and 2860 (99.5%) had conclusive test results. The SARS-CoV-2 prevalences were 2.1% (36/1684) among PEH living sheltered, 0.5% (3/628) among PEH living unsheltered, and 1.3% (7/548) among staff. Reporting fever, cough, or shortness of breath in the last week during symptom screening was 14% sensitive and 89% specific for identifying COVID-19 cases, compared with RT-PCR. Prevalences by shelter ranged 0-27.6%. Repeat testing 3-4 weeks later at 4 shelters documented decreased SARS-CoV-2 prevalences (0-3.9%). Of 24 shelters, 9 completed shelter assessments and implemented IPC measures as part of the COVID-19 response. CONCLUSIONS: PEH living in shelters experienced a higher SARS-CoV-2 prevalence compared with PEH living unsheltered. Facility-wide testing in congregate settings allowed for the identification and isolation of COVID-19 cases, and is an important strategy to interrupt SARS-CoV-2 transmission.

Clinical and Laboratory Findings in Patients With Potential Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reinfection, May-July 2020.

BACKGROUND: We investigated patients with potential severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection in the United States during May-July 2020. METHODS: We conducted case finding for patients with potential SARS-CoV-2 reinfection through the Emerging Infections Network. Cases reported were screened for laboratory and clinical findings of potential reinfection followed by requests for medical records and laboratory specimens. Available medical records were abstracted to characterize patient demographics, comorbidities, clinical course, and laboratory test results. Submitted specimens underwent further testing, including reverse transcription polymerase chain reaction (RT-PCR), viral culture, whole genome sequencing, subgenomic RNA PCR, and testing for anti-SARS-CoV-2 total antibody. RESULTS: Among 73 potential reinfection patients with available records, 30 patients had recurrent coronavirus disease 2019 (COVID-19) symptoms explained by alternative diagnoses with concurrent SARS-CoV-2 positive RT-PCR, 24 patients remained asymptomatic after recovery but had recurrent or persistent RT-PCR, and 19 patients had recurrent COVID-19 symptoms with concurrent SARS-CoV-2 positive RT-PCR but no alternative diagnoses. These 19 patients had symptom recurrence a median of 57 days after initial symptom onset (interquartile range: 47-76). Six of these patients had paired specimens available for further testing, but none had laboratory findings confirming reinfections. Testing of an additional 3 patients with recurrent symptoms and alternative diagnoses also did not confirm reinfection. CONCLUSIONS: We did not confirm SARS-CoV-2 reinfection within 90 days of the initial infection based on the clinical and laboratory characteristics of cases in this investigation. Our findings support current Centers for Disease Control and Prevention (CDC) guidance around quarantine and testing for patients who have recovered from COVID-19.

Establishment of Isolation and Noncongregate Hotels During COVID-19 and Symptom Evolution Among People Experiencing Homelessness-Atlanta, Georgia, 2020.

CONTEXT: Local agencies across the United States have identified public health isolation sites for individuals with coronavirus disease 2019 (COVID-19) who are not able to isolate in residence. PROGRAM: We describe logistics of establishing and operating isolation and noncongregate hotels for COVID-19 mitigation and use the isolation hotel as an opportunity to understand COVID-19 symptom evolution among people experiencing homelessness (PEH). IMPLEMENTATION: Multiple agencies in Atlanta, Georgia, established an isolation hotel for PEH with COVID-19 and noncongregate hotel for PEH without COVID-19 but at risk of severe illness. PEH were referred to the isolation hotel through proactive, community-based testing and hospital-based testing. Daily symptoms were recorded prospectively. Disposition location was recorded for all clients. EVALUATION: During April 10 to September 1, 2020, 181 isolation hotel clients (77 community referrals; 104 hospital referrals) were admitted a median 3 days after testing. Overall, 32% of community referrals and 7% of hospital referrals became symptomatic after testing positive; 83% of isolation hotel clients reported symptoms at some point; 93% completed isolation. Among 302 noncongregate hotel clients, median stay was 18 weeks; 61% were discharged to permanent housing or had a permanent housing discharge plan. DISCUSSION: Overall, a high proportion of PEH completed isolation at the hotel, suggesting a high level of acceptability. Many PEH with COVID-19 diagnosed in the community developed symptoms after testing, indicating that proactive, community-based testing can facilitate early isolation. Noncongregate hotels can be a useful COVID-19 community mitigation strategy by bridging PEH at risk of severe illness to permanent housing.

Addressing advanced HIV disease and mortality in global HIV programming.

INTRODUCTION: The US President's Emergency Plan for AIDS Relief (PEPFAR) was launched to increase access to antiretroviral treatment (ART) among people living with HIV (PLHIV) and to prevent new HIV infections globally. As new infections have decreased in many PEPFAR-supported countries, PEPFAR is increasingly focusing on understanding and decreasing mortality among PLHIV, specifically by addressing advanced HIV disease (AHD) and its attendant opportunistic infections (OIs). Several developments in identifying AHD, in preventing, diagnosing, and treating selected OIs, and in PEPFAR's support for mortality surveillance make this an opportune moment for PEPFAR to address HIV-related mortality. DISCUSSION: AHD upon diagnosis or re-engagement in HIV care is not uncommon, and it substantially increases risk of death from OIs. The World Health Organization provides evidence-based guidelines for a package of interventions for preventing, diagnosing, and treating common OIs, including tuberculosis (TB), cryptococcal meningitis, and severe bacterial infections. PEPFAR facilitates implementation of these guidelines. To identify PLHIV with low CD4, PEPFAR plans to support expanded access to CD4 testing, including a point-of-care assay that differentiates CD4 cell count as a binary of greater than or less than 200 cells/µL. To prevent AHD-related mortality, PEPFAR supports rapid ART initiation with integrase inhibitor-based regimens and implementation and documentation of TB preventive treatment. To diagnose selected OIs, PEPFAR is implementing urine lateral flow lipoarabinomannan use to identify TB among PLHIV who have a CD4 cell count < 200 cells/µL. To treat selected OIs, PEPFAR has focused on improving patient-centered care in TB/HIV co-infection services and scaling up implementation of new drug regimens for cryptococcal meningitis. To better understand mortality, PEPFAR has introduced an indicator, TX_ML, to routinely and systematically categorize outcomes, including deaths, among PLHIV on ART. CONCLUSIONS: PEPFAR is increasing its efforts to identify AHD; to prevent, diagnose, and treat OIs; and to track mortality in its programs. These ongoing efforts, done in collaboration with other stakeholders, seek to decrease mortality among PLHIV.

HIV testing service awareness and service uptake among female heads of household in rural Mozambique: results from a province-wide survey.

BACKGROUND: HIV voluntary counseling and testing (VCT) utilization remains low in many sub-Saharan African countries, particularly in remote rural settings. We sought to identify factors associated with service awareness and service uptake of VCT among female heads of household in rural Zambézia Province of north-central Mozambique which is characterized by high HIV prevalence (12.6%), poverty, and suboptimal health service access and utilization. METHODS: Our population-based survey of female heads of household was administered to a representative two-stage cluster sample using a sampling frame created for use on all national surveys and based on census results. The data served as a baseline measure for the Ogumaniha project initiated in 2009. Survey domains included poverty, health, education, income, HIV stigma, health service access, and empowerment. Descriptive statistics and logistic regression were used to describe service awareness and service uptake of VCT. RESULTS: Of 3708 women surveyed, 2546 (69%) were unaware of available VCT services. Among 1162 women who were aware of VCT, 673 (58%) reported no prior testing. In the VCT aware group, VCT awareness was associated with higher education (aOR = 2.88; 95% CI = 1.61, 5.16), higher income (aOR = 1.41, 95% CI = 1.06, 1.86), higher numeracy (aOR = 1.05, CI 1.03, 1.08), more children < age 5 in the home (aOR = 1.53; 95% CI = 1.07, 2.18), closer proximity to a health facility (aOR = 1.05; 95% CI = 1.03, 1.07), and mobile phone ownership (aOR = 1.37; 95% CI = 1.03, 1.84) (all p-values < 0.04). Having a higher HIV-associated stigma score was the factor most strongly associated with being less likely to test. (aOR = 0.41; 95% CI = 0.23, 0.71; p<0.001). CONCLUSIONS: Most women were unaware of available VCT services. Even women who were aware of services were unlikely to have been tested. Expanded VCT and social marketing of VCT are needed in rural Mozambique with special attention to issues of community-level stigma reduction.

Advanced HIV disease in East Africa and Nigeria, in The African Cohort Study.

BACKGROUND: Earlier antiretroviral therapy (ART) may decrease progression to advanced HIV disease (AHD) with CD4 count of <200 cells per cubic millimeter or clinical sequelae. We assessed factors associated with AHD among people living with HIV before and during the "test and treat" era. SETTING: The African Cohort Study prospectively enrolls adults with and without HIV from 12 clinics in Uganda, Kenya, Tanzania, and Nigeria. METHODS: Enrollment evaluations included clinical history, physical examination, and laboratory testing. Generalized estimating equations were used to estimate adjusted odds ratios and 95% confidence intervals for factors associated with CD4 count of <200 cells per cubic millimeter at study visits. RESULTS: From 2013 to 2021, 3059 people living with HIV with available CD4 at enrollment were included; median age was 38 years [interquartile range: 30-46 years], and 41.3% were men. From 2013 to 2021, the prevalence of CD4 count of <200 cells per cubic millimeter decreased from 10.5% to 3.1%, whereas the percentage on ART increased from 76.6% to 100% ( P <0.001). Factors associated with higher odds of CD4 count of <200 cells per cubic millimeter were male sex (adjusted odds ratio 1.56 [confidence interval: 1.29 to 1.89]), being 30-39 years (1.42 [1.11-1.82]) or older (compared with <30), have World Health Organization stage 2 disease (1.91 [1.48-2.49]) or higher (compared with stage 1), and HIV diagnosis eras 2013-2015 (2.19 [1.42-3.37]) or later (compared with <2006). Compared with ART-naive, unsuppressed participants, being viral load suppressed on ART, regardless of ART duration, was associated with lower odds of CD4 count of <200 cells per cubic millimeter (<6 months on ART: 0.45 [0.34-0.58]). CONCLUSION: With ART scale-up, AHD has declined. Efforts targeting timely initiation of suppressive ART may further reduce AHD risk.

Community stigma endorsement and voluntary counseling and testing behavior and attitudes among female heads of household in Zambézia Province, Mozambique.

BACKGROUND: Some aspects of HIV-related stigma have been shown to be a barrier to HIV services uptake and adherence to antiretroviral treatment (ART). Distinguishing which domains of stigma impact HIV services uptake can enhance the efficacy and efficiency of stigma-reduction interventions. METHODS: The relationships between use of voluntary counseling and testing (VCT) services and two domains of community stigma identified through factor analysis, negative labeling/devaluation and social exclusion, were investigated among 3749 female heads of household. Data were from a general household survey conducted in rural Mozambique. Multivariable logistic regression outcomes were: lifetime VCT use, past-6-months VCT use and VCT endorsement. RESULTS: Thirteen percent (13%) of the participants reported lifetime VCT use, 10% reported past-6-months VCT use and 63% endorsed VCT. A 25-point decrease (from 50 to 25) in the score for negative labeling and devaluation stigma was associated with increased lifetime VCT use (adjusted OR: 1.6, 95% CI: 1.1-2.3) and past-6-months VCT use (adjusted OR: 1.6, 95% CI: 1.1-2.4). A decrease from 50 to 25-points in the score for social exclusion stigma was associated with 1.5 and 1.3-fold increase in odds for past-6-months VCT use and endorsing VCT use, respectively (p < 0.001 for both). Compared with never-testers, considerably high endorsement of VCT use was observed among testers who did not receive HIV test results (adjusted OR: 2.7, 95% CI: 1.6-4.6) and much higher among testers who received results (adjusted OR: 7.3, 95% CI: 4.9-11.0). Distance from health facilities was associated with lower VCT use, but not lower endorsement of VCT. CONCLUSIONS: VCT use and endorsement might differ by domains of stigma held by individuals in the community. Greater uptake and favorable disposition towards use of VCT services in rural settings might be achieved by addressing stigma via domain-specific interventions and by improving the proximity of services and the dissemination of HIV test results.

Modelling the impact of CD4 testing on mortality from TB and cryptococcal meningitis among patients with advanced HIV disease in nine countries.

INTRODUCTION: Despite antiretroviral therapy (ART) scale-up among people living with HIV (PLHIV), those with advanced HIV disease (AHD) (defined in adults as CD4 count <200 cells/mm3 or clinical stage 3 or 4), remain at high risk of death from opportunistic infections. The shift from routine baseline CD4 testing towards viral load testing in conjunction with "Test and Treat" has limited AHD identification. METHODS: We used official estimates and existing epidemiological data to project deaths from tuberculosis (TB) and cryptococcal meningitis (CM) among PLHIV-initiating ART with CD4 <200 cells/mm3 , in the absence of select World Health Organization recommended diagnostic or therapeutic protocols for patients with AHD. We modelled the reduction in deaths, based on the performance of screening/diagnostic testing and the coverage and efficacy of treatment/preventive therapies for TB and CM. We compared projected TB and CM deaths in the first year of ART from 2019 to 2024, with and without CD4 testing. The analysis was performed for nine countries: South Africa, Kenya, Lesotho, Mozambique, Nigeria, Uganda, Zambia, Zimbabwe and the Democratic Republic of Congo. RESULTS: The effect of CD4 testing comes through increased identification of AHD and consequent eligibility for protocols for AHD prevention, diagnosis and management; algorithms for CD4 testing avert between 31% and 38% of deaths from TB and CM in the first year of ART. The number of CD4 tests required per death averted varies widely by country from approximately 101 for South Africa to 917 for Kenya. CONCLUSIONS: This analysis supports retaining baseline CD4 testing to avert deaths from TB and CM, the two most deadly opportunistic infections among patients with AHD. However, national programmes will need to weigh the cost of increasing CD4 access against other HIV-related priorities and allocate resources accordingly.

Rapid antiretroviral therapy initiation in patients with advanced HIV disease: 6-month outcomes of an observational cohort evaluation in Lesotho.

For adults and adolescents, the World Health Organization defines advanced HIV disease (AHD) as a CD4 (cluster of differentiation 4) count of <200 cells/mm3 or a clinical stage 3 or 4 event. We describe clinical outcomes in a cohort of AHD patients at two regional hospitals in Lesotho. From November 2018-June 2019, we prospectively enrolled eligible patients (≥15 years) not on antiretroviral therapy (ART) presenting with WHO-defined AHD into a differentiated model of care for AHD (including rapid ART initiation) and followed them for six months. All patients received Tuberculosis (TB) symptom screening with further diagnostic testing; serum cryptococcal antigen (CrAg) screening was done for CD4 <100 cells/mm3 or WHO clinical stage 3 or 4. Medical record data were abstracted using visit checklist forms. Categorical and continuous variables were summarized using frequencies, percentages, and means, respectively. Kaplan-Meier was used to estimate survival. Of 537 HIV-positive patients screened, 150 (27.9%) had AHD of which 109 were enrolled. Mean age was 38 years and 62 (56.9%) were men. At initial clinic visit, 8 (7.3%) were already on treatment and 33% (36/109) had presumptive TB per symptom screening. Among 39/109 (40.2%) patients screened for CrAg at initial visit, five (12.8%) were CrAg-positive. Among 109 enrolled, 77 (70.6%) initiated ART at their initial clinic visit, while 32 delayed ART initiation (median delay: 14 days). Of the 109 participants enrolled, 76 (69.7%) completed the 6-month follow-up, 17 (15.6%) were lost to follow-up, 5 (4.6%) transferred to other health facilities and 11 (10.1%) died. The 6-month survival was 87.4%; among 74 patients with a viral load result, 6-month viral suppression (<1,000 copies/ml) was 85.1%. Our study found that even after the implementation of Test and Treat of ART in 2016 in Lesotho, over 25% of patients screened had AHD. Patients with AHD had a high prevalence of TB and CrAg positivity, underscoring the need to assess for AHD and rapidly initiate ART within a package of AHD care for optimal patient outcomes.

Molecular xenomonitoring for Wuchereria bancrofti in Culex quinquefasciatus in two districts in Bangladesh supports transmission assessment survey findings.

BACKGROUND: Careful monitoring for recrudescence of Wuchereria bancrofti infection is necessary in communities where mass drug administration (MDA) for the elimination of lymphatic filariasis (LF) as a public health problem has been stopped. During the post-MDA period, transmission assessment surveys (TAS) are recommended by the World Health Organization to monitor the presence of the parasite in humans. Molecular xenomonitoring (MX), a method by which parasite infection in the mosquito population is monitored, has also been proposed as a sensitive method to determine whether the parasite is still present in the human population. The aim of this study was to conduct an MX evaluation in two areas of Bangladesh, one previously endemic district that had stopped MDA (Panchagarh), and part of a non-endemic district (Gaibandha) that borders the district where transmission was most recently recorded. METHODOLOGY/PRINCIPAL FINDINGS: Mosquitoes were systematically collected from 180 trap sites per district and mosquito pools were tested for W. bancrofti using real-time PCR. A total of 23,436 intact mosquitoes, representing 31 species, were collected from the two districts, of which 10,344 (41%) were Culex quinquefasciatus, the vector of W. bancrofti in Bangladesh. All of the 594 pools of Cx. quinquefasciatus tested by real-time PCR were negative for the presence of W. bancrofti DNA. CONCLUSIONS/SIGNIFICANCE: This study suggested the absence of W. bancrofti in these districts. MX could be a sensitive tool to confirm interruption of LF transmission in areas considered at higher risk of recrudescence, particularly in countries like Bangladesh where entomological and laboratory capacity to perform MX is available.

Evaluation of Onchocerciasis Transmission in Tanzania: Preliminary Rapid Field Results in the Tukuyu Focus, 2015.

To compare diagnostic tests for onchocerciasis in a setting that has suppressed transmission, a randomized, age-stratified study was implemented in an area in Tanzania that had received 15 rounds of annual mass drug administration (MDA) with ivermectin. Study participants (N = 948) from 11 villages underwent a questionnaire, skin examination, skin snips, and blood draw. The burden of symptomatic disease was low. Ov-16 antibody rapid diagnostic test (RDT) results were positive in 38 (5.5%) participants, with 1 (0.5%), 1 (0.4%), and 2 (0.8%) in children aged 0-5, 6-10, and 11-15 years, respectively. Despite significant impact of MDA on transmission, the area would have failed to meet World Health Organization serologic criteria for stopping MDA if a full evaluation had been conducted. The specificity of the RDT, which is 97-98%, may result in the identification of a number of false positives that would exceed the current stop MDA threshold.

Duodenal histoplasmosis presenting with upper gastrointestinal bleeding in an AIDS patient.

Gastrointestinal histoplasmosis (GIH) is common in patients with disseminated disease but only rarely comes to clinical attention due to the lack of specific signs and symptoms. We report the unusual case of a 33-year-old Caucasian male with advanced AIDS who presented with upper GI bleeding from diffuse erosions throughout the duodenum. Biopsy of the lesions revealed small bowel mucosa with granulomatous inflammation and macrophages with small intracellular yeasts consistent with disseminated histoplasmosis. The patient demonstrated significant clinical improvement following a two-week course of liposomal amphotericin B. To our knowledge, this is the first case report of duodenal histoplasmosis leading to clinically significant bleeding, manifesting with worsening anemia and melanotic stools. Given our findings, we maintain that GIH should be considered on the differential diagnosis for GI bleeding in AIDS patients at risk, specifically those with advanced immunosuppression (i.e., CD4(+) cell counts <100 cells/mm(3)) who reside in endemic areas (Ohio or Mississippi river valleys) and/or have a prior history of histoplasmosis. For diagnostic evaluation, we recommend checking a urine Histoplasma quantitative antigen EIA as well as upper and/or lower endoscopy with biopsy. We recommend treatment with a two-week course of liposomal amphotericin B followed by indefinite itraconazole.