METHODS: We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders.
FINDINGS: Median CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9).
INTERPRETATION: The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART.
FUNDING: National Institutes of Health.
METHODS: A retrospective review of all cutaneous manifestations of HIV-infected patients with skin biopsy-proven histopathological confirmation, treated in the University of Malaya Medical Centre, from 2016 till 2018, was performed. Clinical characteristics and histopathological correlation of these patients were reviewed.
RESULTS: A total of 38 cases were included where the median age was 40.5 (interquartile range (IQR) 13.3). The median duration of HIV diagnosis to the development of skin disease was 3 years (IQR 7.8). Majority of our patients were male (89.5%, n = 34), and the commonest mode of transmission is men who have sex with men (36.8%, n = 14). Most patients (92.1%, n = 35) had Acquired Immunodeficiency Syndrome when they presented with skin diseases, predominantly non-infectious types (51.4%, n = 19). Commonest skin diseases include eczema (n = 7) and pruritic papular eruption of HIV (n = 6). Papules and plaques were the commonest morphology for both infectious and non-infectious skin diseases. Duration of HIV diagnosis (P = 0.018) and non-compliance to Highly Active Antiretroviral Therapy (HAART) (P = 0.014) were significantly associated with the development of non-infectious skin diseases. Overall, clinicopathological concordance was 84.2% in our centre.
CONCLUSION: A wide spectrum of cutaneous diseases can occur in HIV patients depending on the degree of immunosuppression. skin biopsy along with appropriate stains, and microbiological cultures are important in helping clinicians clinch the right diagnosis.
METHODS: Data collected 2001 to 2016 from PHIVA 10-19 years of age within a regional Asian cohort were analyzed using competing risk time-to-event and Poisson regression analyses to describe the nature and incidence of morbidity events and hospitalizations and identify factors associated with disease-related, treatment-related and overall morbidity. Morbidity was defined according to World Health Organization clinical staging criteria and U.S. National Institutes of Health Division of AIDS criteria.
RESULTS: A total 3,448 PHIVA contributed 17,778 person-years. Median age at HIV diagnosis was 5.5 years, and ART initiation was 6.9 years. There were 2,562 morbidity events and 307 hospitalizations. Cumulative incidence for any morbidity was 51.7%, and hospitalization was 10.0%. Early adolescence was dominated by disease-related infectious morbidity, with a trend toward noninfectious and treatment-related morbidity in later adolescence. Higher overall morbidity rates were associated with a CD4 count <350 cells/µL, HIV viral load ≥10,000 copies/mL and experiencing prior morbidity at age <10 years. Lower overall morbidity rates were found for those 15-19 years of age compared with 10-14 years and those who initiated ART at age 5-9 years compared with <5 or ≥10 years.
CONCLUSIONS: Half of our PHIVA cohort experienced a morbidity event, with a trend from disease-related infectious events to treatment-related and noninfectious events as PHIVA age. ART initiation to prevent immune system damage, optimize virologic control and minimize childhood morbidity are key to limiting adolescent morbidity.
CASE REPORT: We describe a case of a 33 years old gentleman who was clinically diagnosed as acute appendicitis at initial presentation in view of a one-week history of fever, right lower quadrant abdominal pain- and guarding at right iliac fossa. He had thrombocytopenia and lymphopenia on presentation. Mesenteric lymphadenitis and small bowel lesion were found intraoperatively, which was respectively biopsied and resected. Histopathological result confirms disseminated histoplasmosis. Retroviral screen was positive. He was treated with amphotericin B for one week, subsequently switched to oral itraconazole, followed by initiation of highly active antiretroviral therapy (HAART).
DISCUSSION: This case illustrates the various nature of histoplasmosis presentation. A high index of suspicion is needed to clinch the diagnosis and subsequently institute prompt treatment as disseminated disease can be fatal if left untreated in an immunosuppressed host.
METHODS: Prospectively collected longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan, and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count, and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of Centers for Disease Control and Prevention category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post therapy, evaluated by linear and logistic regression, respectively.
RESULTS: Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median: 413 days, interquartile range: 169-672 days). Patients >40 years demonstrated smaller immunological increases (P = 0.002) and higher risk of clinical deterioration (hazard ratio = 2.17; P = 0.008). Patients with baseline CD4 cell counts >200 cells per microliter had lower risk of clinical deterioration (hazard ratio = 0.373; P = 0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (P = 0.024). A total of 530 patients (48.0% of eligible) were included in virological analyses with no differences in response found between genotypes.
CONCLUSIONS: Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared with subtype B-infected counterparts. Clinical deterioration was associated with low baseline CD4 counts and older age. The lack of differences in virologic outcomes suggests that all patients have opportunities for virological suppression.
METHODS: HIV-infected adults enrolled in the TREAT Asia HIV Observational Database were eligible if they had an HIV RNA measurement documented at the time of ART initiation. The dataset was randomly split into a derivation data set (75% of patients) and a validation data set (25%). Factors associated with pre-treatment HIV RNA <100,000 copies/mL were evaluated by logistic regression adjusted for study site. A prediction model and prediction scores were created.
RESULTS: A total of 2592 patients were enrolled for the analysis. Median [interquartile range (IQR)] age was 35.8 (29.9-42.5) years; CD4 count was 147 (50-248) cells/mm3; and pre-treatment HIV RNA was 100,000 (34,045-301,075) copies/mL. Factors associated with pre-treatment HIV RNA <100,000 copies/mL were age <30 years [OR 1.40 vs. 41-50 years; 95% confidence interval (CI) 1.10-1.80, p = 0.01], body mass index >30 kg/m2(OR 2.4 vs. <18.5 kg/m2; 95% CI 1.1-5.1, p = 0.02), anemia (OR 1.70; 95% CI 1.40-2.10, p 350 cells/mm3(OR 3.9 vs. <100 cells/mm3; 95% CI 2.0-4.1, p 2000 cells/mm3(OR 1.7 vs. <1000 cells/mm3; 95% CI 1.3-2.3, p 25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA <100,000 copies/mL among derivation patients.
CONCLUSION: A model prediction for pre-treatment HIV RNA <100,000 copies/mL produced an area under the ROC curve of 0.70. A larger sample size for prediction model development as well as for model validation is warranted.
CASE PRESENTATION: A 52-year-old Malay gentleman, with hepatitis C virus and HIV infection was admitted to the intensive care unit for severe lactic acidosis, with concurrent Escherichia coli bacteremia with multiorgan dysfunction. The patient was started on highly active antiretroviral therapy, which included tenofovir, 5 weeks before presentation. Antimicrobial therapy, continuous veno-venous hemofiltration, and other supportive treatments were instituted. However, the patient eventually succumbed to his illness.
CONCLUSIONS: It is essential for clinicians to be able to recognize the signs and symptoms of lactic acidosis in NRTIs treated HIV patients, as an early diagnosis is important to institute treatment.