Barriers to Initiation of Pediatric HIV Treatment in Uganda: A Mixed-Method Study

Although the advantages of early infant HIV diagnosis and treatment initiation are well established, children often present late to HIV programs in resource-limited settings. We aimed to assess factors related to the timing of treatment initiation among HIV-infected children attending three clinical sites in Uganda. Clinical and demographic determinants associated with early disease (WHO clinical stages 1-2) or late disease (stages 3-4) stage at presentation were assessed using multilevel logistic regression. Additionally, semistructured interviews with caregivers and health workers were conducted to qualitatively explore determinants of late disease stage at presentation. Of 306 children initiating first-line regimens, 72% presented late. Risk factors for late presentation were age below 2 years old (OR 2.83, P = 0.014), living without parents (OR 3.93, P = 0.002), unemployment of the caregiver (OR 4.26, P = 0.001), lack of perinatal HIV prophylaxis (OR 5.66, P = 0.028), and high transportation costs to the clinic (OR 2.51, P = 0.072). Forty-nine interviews were conducted, confirming the identified risk factors and additionally pointing to inconsistent referral from perinatal care, caregivers' unawareness of HIV symptoms, fear, and stigma as important barriers. The problem of late disease at presentation requires a multifactorial approach, addressing both health system and individual-level factors

Immunogenicity of an additional mRNA-1273 SARS-CoV-2 vaccination in people with HIV with hyporesponse after primary vaccination

Background:The COVIH study is a prospective coronavirus disease 2019 (COVID-19) vaccination study in 1154 people with HIV (PWH), of whom 14% showed reduced antibody levels after primary vaccination. We evaluated whether an additional vaccination boosts immune responses in these hyporesponders. Methods: The primary end point was the increase in antibodies 28 days after additional mRNA-1273 vaccination. Secondary end points included neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity. Results:Of the 66 participants, 40 previously received 2 doses ChAdOx1-S, 22 received 2 doses BNT162b2, and 4 received a single dose Ad26.COV2.S. The median age was 63 years (interquartile range [IQR], 60–66), 86% were male, and median CD4 + T-cell count was 650/μL (IQR, 423–941). The mean S1-specific antibody level increased from 35 binding antibody units (BAU)/ mL (95% confidence interval [CI], 24–46) to 4317 BAU/mL (95% CI, 3275–5360) (P &lt; .0001). Of all participants, 97% showed an adequate response and the 45 antibody-negative participants all seroconverted. A significant increase in the proportion of PWH with ancestral S-specific CD4 + T cells (P = .04) and S-specific B cells (P = .02) was observed. Conclusions:An additional mRNA-1273 vaccination induced a robust serological response in 97% of PWH with a hyporesponse after primary vaccination.</p

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19(1,2), host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases(3-7). They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.Radiolog

HIV drug resistance among adults and children in sub-Saharan Africa

One of the biggest medical accomplishments of the beginning of this century has been the expanded access to life-saving antiretroviral treatment for HIV-infected people living in sub-Saharan Africa. A potential downside of the large-scale exposure to antiretroviral drugs is the emergence of HIV drug resistance. This risk is increased by the weak health systems in many African countries, characterized by poor infrastructure, intermittent drug supply, and shortage of skilled staff. In order to evaluate the extent of HIV drug resistance in Africa, the PharmAccess African Studies to Evaluate Resistance (PASER) network was established in 2006. In six countries - Kenya, Nigeria, South Africa, Uganda, Zambia and Zimbabwe - over fifteen clinics participated in observational studies among HIV-infected adults. In Uganda, a pediatric study was initiated to investigate the development of HIV drug resistance among children. The studies included in this thesis were conducted as part of the PASER adult and pediatric programs

Behandeling voor endocarditis afronden met orale antibiotica?

The recently published POET trial breaks with the established paradigm of long-term, high-dose intravenous antibiotics for all patients with endocarditis. The study involved 400 Danish patients who had endocarditis caused by Gram-positive micro-organisms and who had a favourable response to initial intravenous therapy. The IV to oral switch appeared to be non-inferior to continuing intravenous treatment. From the perspective of antibiotic stewardship, this is a step forward because a shorter period of intravenous therapy reduces catheter-associated complications. However, treating clinicians should realise that the study had strict inclusion criteria and that its results apply to selected, low-risk patients only

Herpes zoster-associated encephalitis in a patient undergoing CAPD: case report and literature review

Neurological complications of varicella zoster virus (VZV) reactivation have rarely been described in dialysis patients. We report a case of a continuous ambulatory peritoneal dialysis (CAPD) patient who developed herpes zoster encephalitis. The patient was treated with acyclovir and steroids and had a slow but complete return to her prior cognitive status. The available literature is reviewed and the differential diagnosis with acyclovir toxicity is discusse

Global response to HIV: treatment as prevention, or treatment for treatment?

The concept of "treatment as prevention" has emerged as a means to curb the global HIV epidemic. There is, however, still ongoing debate about the evidence on when to start antiretroviral therapy in resource-poor settings. Critics have brought forward multiple arguments against a "test and treat" approach, including the potential burden of such a strategy on weak health systems and a presumed lack of scientific support for individual patient benefit of early treatment initiation. In this article, we highlight the societal and individual advantages of treatment as prevention in resource-poor settings. We argue that the available evidence renders the discussion on when to start antiretroviral therapy unnecessary and that, instead, efforts should be aimed at offering treatment as soon as possibl

Thuisbehandeling met intraveneuze antibiotica

Treatment of infections with intravenous antibiotics does not always require hospital care; specialized home care nurses can administer parenteral treatment at home. Dedicated Outpatient Parenteral Antimicrobial Therapy (OPAT) teams are emerging in an increasing number of hospitals in the Netherlands to supervise treatment selection and provide safety monitoring for patients with home treatment. This specialized, nurse driven team facilitates home treatment by collaborating with infectious disease specialists, pharmacy and home care teams, as well as the patient and treating physician. Demand for OPAT treatment is increasing, but currently a structural financial endorsement is lacking in the Netherlands. A solid financial structure will be essential to ensure safe and effective parenteral antimicrobial therapy at home, which can relieve the strain on hospital care