The Impact of Telemedicine on Human Immunodeficiency Virus (HIV)-Related Clinical Outcomes During the COVID-19 Pandemic.

The coronavirus disease of 2019 (COVID-19) pandemic exacerbated barriers to care for people living with human immunodeficiency virus (HIV) (PLWH). The quick uptake of telemedicine in the outpatient setting provided promise for care continuity. In this study, we compared appointment and laboratory no-show rates in an urban outpatient HIV clinic during three time periods: (1) Pre-COVID-19: 9/15/2019-3/14/2020 (predominately in-person), (2) "Early" COVID-19: 3/15/2020-9/14/2020 (predominately telemedicine), and (3) "Later" COVID-19: 9/15/2020-3/14/2021 (mixed in-person/telemedicine). Multivariable logistic regression models evaluated the two study hypotheses: (i) equivalence of Period 2 with Period 1 and of Period 3 with Period 1 and (ii) improved outcomes with telemedicine over in-person visits. No-show rates were 1% in Period 1, 4% in Period 2, and 18% in Period 3. Compared to the pre-pandemic period, individuals had a higher rate of appointment no-shows during Period 2 [OR (90% CI): 7.67 (2.68, 21.93)] and 3 [OR (90% CI): 30.91 (12.83 to 75.06). During the total study period, those with telemedicine appointments were less likely to no-show than those with in-person appointments [OR (95% CI): 0.36 (0.16-0.80), p = 0.012]. There was no statistical difference between telemedicine and in-person appointments for laboratory completion rates. Our study failed to prove that no-show rates before and during the pandemic were similar; in fact, no-show rates were higher during both the early and later pandemic. Overall, telemedicine was associated with lower no-show rates compared to in-person appointments. In future pandemics, telemedicine may be a valuable component to maintain care in PLWH.

Breath ammonia and ethanol increase in response to a high protein challenge.

Quantifying changes in ammonia and ethanol in blood and body fluid assays in response to food is cumbersome. We used breath analysis of ammonia, ethanol, hydrogen (an accepted standard of gut transit) and acetone to investigate gastrointestinal physiology. In 30 healthy participants, we measured each metabolite serially over 6 h in control and high protein trials. Two-way repeated measures ANOVA compared treatment (control versus intervention), change from baseline to maximum and interaction of treatment and time change. Interaction was significant for ammonia (p < 0.0001) and hydrogen (p < 0.0001). We describe the dynamic measurement of multiple metabolites in response to an oral challenge.

Musculoskeletal manifestations of syphilis in adults: secondary syphilis presenting with ankle inflammatory arthritis and bone involvement with calvarial and sternal lesions. What the rheumatologist needs to know.

Although the incidence of syphilis reached a historic low in 2000, the number of incident cases has since increased in men and women across the USA. In 2019, men who have sex with men (MSM) accounted for 57% of all primary and secondary (P&S) syphilis cases, and about half of MSM with P&S syphilis are living with human immunodeficiency virus (HIV) infection. Days after infection, Treponema pallidum disseminates and invades tissues distant from the site of inoculation. Once the spirochete disseminates, the host develops an inflammatory response; diagnosis requires a high level of suspicion since syphilis may affect the skin, musculoskeletal, cardiovascular, and central nervous systems. We report a 61-year-old man with virally suppressed HIV infection who presented with polyarthralgia, chest pain, and weight loss, diagnosed with secondary syphilis, manifesting with ankle inflammatory arthritis and bone involvement, of the calvarium and manubrium. Early and late syphilis in adults can manifest with articular and periarticular pathologies, including inflammatory arthritis, tenosynovitis, periostitis, and myositis. Higher clinical suspicion is needed for prompt diagnosis of syphilis in patients who are at risk and suspected of having an autoimmune disease. This report includes a review of the musculoskeletal manifestations of syphilis.

Absence of detectable xenotropic murine leukemia virus-related virus in plasma or peripheral blood mononuclear cells of human immunodeficiency virus type 1-infected blood donors or individuals in Africa.

BACKGROUND: Since the identification of xenotropic murine leukemia virus-related virus (XMRV) in prostate cancer patients in 2006 and in chronic fatigue syndrome patients in 2009, conflicting findings have been reported regarding its etiologic role in human diseases and prevalence in general populations. In this study, we screened both plasma and peripheral blood mononuclear cells (PBMNCs) collected in Africa from blood donors and human immunodeficiency virus Type 1 (HIV-1)-infected individuals to gain evidence of XMRV infection in this geographic region. STUDY DESIGN AND METHODS: A total of 199 plasma samples, 19 PBMNC samples, and 50 culture supernatants from PBMNCs of blood donors from Cameroon found to be infected with HIV-1 and HIV-1 patients from Uganda were screened for XMRV infection using a sensitive nested polymerase chain reaction (PCR) or reverse transcription (RT)-PCR assay. RESULTS: Using highly sensitive nested PCR or RT-PCR and real-time PCR assays capable of detecting at least 10 copies of XMRV plasmid DNA per reaction, none of the 268 samples tested were found to be XMRV DNA or RNA positive. CONCLUSIONS: Our results failed to demonstrate the presence of XMRV infection in African blood donors or individuals infected with HIV-1. More studies are needed to understand the prevalence, epidemiology, and geographic distribution of XMRV infection worldwide.

Three-year outcome data of second-line antiretroviral therapy in Ugandan adults: good virological response but high rate of toxicity.

OBJECTIVE: To evaluate the safety and virological response to lopinavir/ritonavir containing second-line therapy after failing a first line nonnucleoside reverse transcriptase inhibitor (NNRTI) based regimen. DESIGN: Prospective 36 months cohort study of patients switched to zidovudine/stavudine plus didanosine plus lopinavir/ritonavir capsules as second-line regimen. METHODOLOGY: Structured interview, medical examination, and laboratory assessment performed every 6 months. RESULTS: We enrolled 40 patients; 1 died and 3 were lost to follow-up. Median CD4+ count at baseline was 108 cell/microL, median log viral load was 4.8 copies/mL. Sixteen (40%) patients had baseline genotypic resistant test, 14 (87%) had lamivudine resistance mutations, and all had NNRTIs resistance mutations. At month 36, 82% of the patients achieved viral suppression (<400 copies/ mL) and the median increase in CD4+ count was 214 cell/microL, (interquartile range: 128-295). Twenty-five patients (62%) experienced at least one adverse event. CONCLUSIONS: Our study confirms lopinavir/ ritonavir-based second-line regimen but with a high rate of toxicities.

Repeated Measures of Blood and Breath Ammonia in Response to Control, Moderate and High Protein Dose in Healthy Men.

Ammonia physiology is important to numerous disease states including urea cycle disorders and hepatic encephalopathy. However, many unknowns persist regarding the ammonia response to common and potentially significant physiologic influences, such as food. Our aim was to evaluate the dynamic range of ammonia in response to an oral protein challenge in healthy participants. We measured blood and breath ammonia at baseline and every hour for 5.5 hours. Healthy men (N = 22, aged 18 to 24 years) consumed a 60 g protein shake (high dose); a subset of 10 consumed a 30 g protein shake (moderate dose) and 12 consumed an electrolyte drink containing 0 g protein (control). Change in blood ammonia over time varied by dose (p = 0.001). Difference in blood ammonia was significant for control versus high (p = 0.0004) and moderate versus high (p = 0.03). Change in breath ammonia over time varied by dose (p < 0.0001). Difference in breath ammonia was significant for control versus moderate (p = 0.03) and control versus high (p = 0.0003). Changes in blood and breath ammonia were detectable by fast, minimally-invasive (blood) or non-invasive (breath) point-of-care ammonia measurement methods. These pilot data may contribute to understanding normal ammonia metabolism. Novel measurement methods may aid research into genetic and metabolic ammonia disorders.

Response to antiretroviral therapy in HIV-infected patients attending a public, urban clinic in Kampala, Uganda.

BACKGROUND: Access to antiretroviral therapy and human immunodeficiency virus (HIV) care is increasing in resource-limited settings. We evaluated clinical, behavioral, and demographic risk factors associated with virologic suppression in a public, urban clinic in Kampala, Uganda. METHODS: We conducted a cross-sectional, observational study of 137 HIV-infected patients who were receiving antiretroviral therapy at the infectious diseases clinic at Mulago Hospital (Kampala). We measured the prevalence of viral suppression, evaluated risk factors associated with virologic failure, and documented phenotypic resistance patterns and genotypic mutations. RESULTS: A total of 91 (66%) of 137 participants had an undetectable viral load (< 400 copies/mL) after a median duration of 38 weeks (interquartile range, 24-62 weeks) of antiretroviral therapy. Median CD4 cell count was 163 cells/mm3 (interquartile range, 95-260 cells/mm3). The majority of the patients (91%) were treated with nonnucleoside reverse-transcriptase inhibitor-based 3-drug regimens. In multivariate analysis, treatment with the first antiretroviral regimen was associated with viral suppression (odds ratio, 2.6; 95% confidence interval, 1.1-6.1). In contrast, a history of unplanned treatment interruption was associated with virologic treatment failure (odds ratio, 0.2; 95% confidence interval, 0.1-0.6). Of 124 participants treated with nonnucleoside reverse-transcriptase inhibitors, 27 (22%) were documented to have experienced virologic treatment failure. The most common mutation detected was K103N (found in 14 of 27 patients with virologic treatment failure). CONCLUSIONS: Although many HIV-infected people treated in Kampala, Uganda, have advanced HIV disease, the majority of patients who received antiretroviral therapy experienced viral suppression and clinical benefit. Because of the frequent use of nonnucleoside reverse-transcriptase inhibitor-based therapy, the majority of resistance was against this drug class. In resource-limited settings, initiation of therapy with a potent, durable regimen, accompanied by stable drug supplies, will optimize the likelihood of viral suppression.

Clinical illness as a marker for initiation of HIV antiretroviral therapy in a rural setting, Rakai, Uganda.

The aim of this study is to assess whether HIV-related illness and World Health Organization (WHO) clinical stage can be used to guide initiation of antiretroviral therapy (ART) in rural Rakai District, Uganda. A retrospective cohort analysis of 910 HIV-seroprevalent individuals randomly sampled from a community cohort was conducted. The associations between HIV-related clinical illness and HIV viral loads >55,000 copies/mL and death were evaluated as a guide for initiation of ART. Reporting one or more HIV-related illnesses was associated with high specificity for identifying HIV viral load >55,000 copies/mL and predicting death within 30 months. There were more deaths in those with one symptom at baseline (16.3%) and two or more symptoms (25.0%) than in those reporting no symptoms (9.6%; P = 0.001).HIV-related illness and WHO stage predicted disease progression. The specificity of clinical illness to predict viral load >55,000 copies/mL was high and could be used to rule in HIV disease requiring ART.

Clinical utility of breath ammonia for evaluation of ammonia physiology in healthy and cirrhotic adults.

Blood ammonia is routinely used in clinical settings to assess systemic ammonia in hepatic encephalopathy and urea cycle disorders. Despite its drawbacks, blood measurement is often used as a comparator in breath studies because it is a standard clinical test. We sought to evaluate sources of measurement error and potential clinical utility of breath ammonia compared to blood ammonia. We measured breath ammonia in real time by quartz enhanced photoacoustic spectrometry and blood ammonia in 10 healthy and 10 cirrhotic participants. Each participant contributed 5 breath samples and blood for ammonia measurement within 1 h. We calculated the coefficient of variation (CV) for 5 breath ammonia values, reported medians of healthy and cirrhotic participants, and used scatterplots to display breath and blood ammonia. For healthy participants, mean age was 22 years (±4), 70% were men, and body mass index (BMI) was 27 (±5). For cirrhotic participants, mean age was 61 years (±8), 60% were men, and BMI was 31 (±7). Median blood ammonia for healthy participants was within normal range, 10 µmol L(-1) (interquartile range (IQR), 3-18) versus 46 µmol L(-1) (IQR, 23-66) for cirrhotic participants. Median breath ammonia was 379 pmol mL(-1) CO2 (IQR, 265-765) for healthy versus 350 pmol mL(-1) CO2 (IQR, 180-1013) for cirrhotic participants. CV was 17 ± 6%. There remains an important unmet need in the evaluation of systemic ammonia, and breath measurement continues to demonstrate promise to fulfill this need. Given the many differences between breath and blood ammonia measurement, we examined biological explanations for our findings in healthy and cirrhotic participants. We conclude that based upon these preliminary data breath may offer clinically important information this is not provided by blood ammonia.

Total lymphocyte count and hemoglobin combined in an algorithm to initiate the use of highly active antiretroviral therapy in resource-limited settings.

OBJECTIVE: To develop clinical algorithms that improve the sensitivity of surrogate markers to initiate the use of highly active antiretroviral therapy (HAART) in resource-limited settings. DESIGN: A retrospective evaluation of total lymphocyte counts (TLC) and hemoglobin to predict the CD4 lymphocyte count. METHODS: A total of 3269 members of the Johns Hopkins HIV observational cohort contributed 22 690 paired observations of CD4 lymphocyte counts and TLC. Two methods were used to evaluate the effect of combining TLC and hemoglobin to predict CD4 cell counts below 200 cells/mm3 before the initiation of HAART in 1451 participants; 55.3% of participants had CD4 cell counts below 200 cells/mm3. RESULTS: TLC below 1200 cells/mm3 and hemoglobin below 12 g/dl significantly predicted CD4 cell counts below 200 cells/mm3. For TLC alone sensitivity was 70.7% and specificity was 81.7%. For both men and women, we chose a TLC lower cutoff point of 1200 cells/mm3, an upper cutoff point of 2000 cells/mm3, and hemoglobin of 12 g/dl. For men, method I generated sensitivity of 78.0% and specificity of 77.5%. Method II improved specificity to 81.8%. For women, method I increased sensitivity to 85.6% and decreased specificity to 64.1%. Method II improved specificity to 81.4%. CONCLUSION: TLC below 1200 cells/mm3 were associated with CD4 cell counts below 200 cells/mm3 as in the WHO guidelines, but sensitivity was low. Adding hemoglobin to TLC increased sensitivity, thereby reducing the risk of false-negative results. Our model may serve as a template for the development of algorithms to initiate the use of HAART in resource-limited settings.

Shiga toxin-producing Escherichia coli as a possible etiological agent of chronic diarrhea.

We identified Shiga toxin-producing Escherichia coli (STEC) as the likely etiologic pathogen for chronic diarrhea in 2 patients, 1 of whom was immunocompromised with acquired immunodeficiency syndrome, and 1 of whom was immunocompetent. Both were treated with antibiotics, and neither developed systemic complications of the infection. These cases suggest that STEC infection should be considered in the differential diagnosis of chronic diarrhea.

Fast and accurate exhaled breath ammonia measurement.

This exhaled breath ammonia method uses a fast and highly sensitive spectroscopic method known as quartz enhanced photoacoustic spectroscopy (QEPAS) that uses a quantum cascade based laser. The monitor is coupled to a sampler that measures mouth pressure and carbon dioxide. The system is temperature controlled and specifically designed to address the reactivity of this compound. The sampler provides immediate feedback to the subject and the technician on the quality of the breath effort. Together with the quick response time of the monitor, this system is capable of accurately measuring exhaled breath ammonia representative of deep lung systemic levels. Because the system is easy to use and produces real time results, it has enabled experiments to identify factors that influence measurements. For example, mouth rinse and oral pH reproducibly and significantly affect results and therefore must be controlled. Temperature and mode of breathing are other examples. As our understanding of these factors evolves, error is reduced, and clinical studies become more meaningful. This system is very reliable and individual measurements are inexpensive. The sampler is relatively inexpensive and quite portable, but the monitor is neither. This limits options for some clinical studies and provides rational for future innovations.

Changes in the concentration of breath ammonia in response to exercise: a preliminary investigation.

Breath ammonia has proven to be a difficult compound to measure accurately. The goal of this study was to evaluate the effects that the physiological intervention, exercise, had on the levels of breath ammonia. The effects of vigorous exercise (4000 m indoor row) in 13 participants were studied and increases in breath ammonia were observed in all participants. Mean pre-exercise concentrations of ammonia were 670 pmol ml(-1) CO2 (SD, 446) and these concentrations increased to post-exercise maxima of 1499 pmol ml(-1) CO2 (SD, 730), p < 0.0001. The mean increase in ammonia concentrations from pre-exercise to maximum achieved in conditioned (1362 pmol ml(-1) CO2) versus non-conditioned rowers (591 pmol ml(-1) CO2) were found to be statistically different, p = 0.029. Taken together, these results demonstrate our ability to repeatedly measure the influence of exercise on the concentration of breath ammonia.

Factors influencing breath ammonia determination.

Amongst volatile compounds (VCs) present in exhaled breath, ammonia has held great promise and yet it has confounded researchers due to its inherent reactivity. Herein we have evaluated various factors in both breath instrumentation and the breath collection process in an effort to reduce variability. We found that the temperature of breath sampler and breath sensor, mouth rinse pH, and mode of breathing to be important factors. The influence of the rinses is heavily dependent upon the pH of the rinse. The basic rinse (pH 8.0) caused a mean increase of the ammonia concentration by 410 ± 221 ppb. The neutral rinse (pH 7.0), slightly acidic rinse (pH 5.8), and acidic rinse (pH 2.5) caused a mean decrease of the ammonia concentration by 498 ± 355 ppb, 527 ± 198 ppb, and 596 ± 385 ppb, respectively. Mode of breathing (mouth-open versus mouth-closed) demonstrated itself to have a large impact on the rate of recovery of breath ammonia after a water rinse. Within 30 min, breath ammonia returned to 98 ± 16% that of the baseline with mouth open breathing, while mouth closed breathing allowed breath ammonia to return to 53 ± 14% of baseline. These results contribute to a growing body of literature that will improve reproducibly in ammonia and other VCs.