Quality of Care for HIV Infection Provided by Ryan White Program-Supported versus Non-Ryan White Program-Supported Facilities

BACKGROUND: The Ryan White HIV/AIDS Care Act (now the Treatment Modernization Act; Ryan White Program, or RWP) is a source of federal public funding for HIV care in the United States. The Health Services and Resources Administration requires that facilities or providers who receive RWP funds ensure that HIV health services are accessible and delivered according to established HIV-related treatment guidelines. We used data from population-based samples of persons in care for HIV infection in three states to compare the quality of HIV care in facilities supported by the RWP, with facilities not supported by the RWP. METHODOLOGY/PRINCIPAL FINDINGS: Within each area (King County in Washington State; southern Louisiana; and Michigan), a probability sample of patients receiving care for HIV infection in 1998 was drawn. Based on medical records abstraction, information was collected on prescription of antiretroviral therapy according to treatment recommendations, prescription of prophylactic therapy, and provision of recommended vaccinations and screening tests. We calculated population-level estimates of the extent to which HIV care was provided according to then-current treatment guidelines in RWP-supported and non-RWP-supported facilities. For all treatment outcomes analyzed, the compliance with care guidelines was at least as good for patients who received care at RWP-supported (vs non-RWP supported) facilities. For some outcomes in some states, delivery of recommended care was significantly more common for patients receiving care in RWP-supported facilities: for example, in Louisiana, patients receiving care in RWP-supported facilities were more likely to receive indicated prophylaxis for Pneumocystis jirovecii pneumonia and Mycobacterium avium complex, and in all three states, women receiving care in RWP-supported facilities were more likely to have received an annual Pap smear. CONCLUSIONS/SIGNIFICANCE: The quality of HIV care provided in 1998 to patients in RWP-supported facilities was of equivalent or better quality than in non-RWP supported facilities; however, there were significant opportunities for improvement in all facility types. Data from population-based clinical outcomes surveillance data can be used as part of a broader strategy to evaluate the quality of publicly-supported HIV care

The persisting burden of invasive pneumococcal disease in HIV patients: an observational cohort study

<p>Abstract</p> <p>Background</p> <p>The increasing use of highly active antiretroviral therapy (HAART) and pneumococcal immunization along with shifting community exposures may have altered the burden of <it>Streptococcus pneumoniae </it>disease in HIV-infected persons. We describe the burden and risk factors for pneumococcal disease in the modern era of HIV care and evaluate the use of a 23-valent pneumococcal polysaccharide vaccine (PPV-23).</p> <p>Methods</p> <p>The incidence of invasive pneumococcal disease (IPD) between January 1^st, 2000 and January 1^st, 2010 in a regional HIV population in Southern Alberta, Canada was determined by linking comprehensive laboratory and hospital surveillance data. Clinical and epidemiologic data including risk factors for <it>S. pneumoniae</it>, history of pneumococcal immunization, serotypes of infections, and length of any hospitalizations for pneumococcal disease were evaluated with multivariate analysis. CD4 count and viral load at immunization were evaluated with a nested case-control analysis.</p> <p>Results</p> <p>In 1946 HIV-patients with 11,099 person-years of follow up, there were 68 distinct episodes of pneumococcal disease occurring in 50 patients. Increased risk was seen if female, age >60, Aboriginal ethnicity, lower education, injection drug use, smoking, nadir CD4 <200/μL, chronic obstructive pulmonary disease, and hepatitis C. Overall, the incidence of IPD was 342/100,000 person-years and was reduced to 187/100,000 within three years of PPV-23 immunization (P < 0.01). Although 78% of patients received PPV-23, 74% of IPD episodes were caused by PPV-23 serotypes. In a case-control analysis, HIV viral load at immunization was significantly predictive of PPV-23 failure, while CD4 count was not. 80% of IPD cases required hospitalization: median length of stay was 7 days (range: 1-71); four patients died.</p> <p>Conclusions</p> <p>Despite universal access to intensive measures to prevent pneumococcal disease including the widespread use of HAART and PPV-23 immunization, the incidence of IPD remains high in HIV patients with its associated morbidity and mortality.</p

Persistent High Burden of Invasive Pneumococcal Disease in South African HIV-Infected Adults in the Era of an Antiretroviral Treatment Program

Highly active antiretroviral treatment (HAART) programs have been associated with declines in the burden of invasive pneumococcal disease (IPD) in industrialized countries. The aim of this study was to evaluate trends in IPD hospitalizations in HIV-infected adults in Soweto, South Africa, associated with up-scaling of the HAART program from 2003 to 2008.Laboratory-confirmed IPD cases were identified from 2003 through 2008 through an existing surveillance program. The period 2003-04 was designated as the early-HAART era, 2005-06 as the intermediate-HAART era and 2007-08 as the established-HAART era. The incidence of IPD was compared between the early-HAART and established-HAART eras in HIV-infected and-uninfected individuals.A total of 2,567 IPD cases among individuals older than 18 years were reported from 2003 through 2008. Overall incidence of IPD (per 100,000) did not change during the study period in HIV-infected adults (207.4 cases in the early-HAART and 214.0 cases in the established-HAART era; p = 0.55). IPD incidence, actually increased 1.16-fold (95% CI: 1.01; 1.62) in HIV-infected females between the early-and established-HAART eras (212.1 cases and 246.2 cases, respectively; p = 0.03). The incidence of IPD remained unchanged in HIV-uninfected adults across the three time periods.Despite a stable prevalence of HIV and the increased roll-out of HAART for treatment of AIDS patients in our setting, the burden of IPD has not decreased among HIV-infected adults. The study indicates a need for ongoing monitoring of disease and HAART program effectiveness to reduce opportunistic infections in African adults with HIV/AIDS, as well as the need to consider alternate strategies including pneumococcal conjugate vaccine immunization for the prevention of IPD in HIV-infected adults

Discontinuation of Pneumocystis jirovecii Pneumonia Prophylaxis with CD4 Count <200 Cells/µL and Virologic Suppression: A Systematic Review

HIV viral load (VL) is currently not part of the criteria for Pneumocystis jirovecii pneumonia (PCP) prophylaxis discontinuation, but suppression of plasma viremia with antiretroviral therapy may allow for discontinuation of PCP prophylaxis even with CD4 count <200 cells/µL.A systematic review was performed to determine the incidence of PCP in HIV-infected individuals with CD4 count <200 cells/µL and fully suppressed VL on antiretroviral therapy but not receiving PCP prophylaxis.Four articles examined individuals who discontinued PCP prophylaxis with CD4 count <200 cells/µL in the context of fully suppressed VL on antiretroviral therapy. The overall incidence of PCP was 0.48 cases per 100 person-years (PY) (95% confidence interval (CI) (0.06-0.89). This was lower than the incidence of PCP in untreated HIV infection (5.30 cases/100 PY, 95% CI 4.1-6.8) and lower than the incidence in persons with CD4 count <200 cells/µL, before the availability of highly active antiretroviral therapy (HAART), who continued prophylaxis (4.85/100 PY, 95% CI 0.92-8.78). In one study in which individuals were stratified according to CD4 count <200 cells/µL, there was a greater risk of PCP with CD4 count ≤100 cells/µL compared to 101-200 cells/µL.Primary PCP prophylaxis may be safely discontinued in HIV-infected individuals with CD4 count between 101-200 cells/µL provided the VL is fully suppressed on antiretroviral therapy. However, there are inadequate data available to make this recommendation when the CD4 count is ≤100 cells/µL. A revision of guidelines on primary PCP prophylaxis to include consideration of the VL is merited

The Hepatitis E Virus Polyproline Region Is Involved in Viral Adaptation

Genomes of hepatitis E virus (HEV), rubivirus and cutthroat virus (CTV) contain a region of high proline density and low amino acid (aa) complexity, named the polyproline region (PPR). In HEV genotypes 1, 3 and 4, it is the only region within the non-structural open reading frame (ORF1) with positive selection (4–10 codons with dN/dS>1). This region has the highest density of sites with homoplasy values >0.5. Genotypes 3 and 4 show ∼3-fold increase in homoplastic density (HD) in the PPR compared to any other region in ORF1, genotype 1 does not exhibit significant HD (p<0.0001). PPR sequence divergence was found to be 2-fold greater for HEV genotypes 3 and 4 than for genotype 1. The data suggest the PPR plays an important role in host-range adaptation. Although the PPR appears to be hypervariable and homoplastic, it retains as much phylogenetic signal as any other similar sized region in the ORF1, indicating that convergent evolution operates within the major HEV phylogenetic lineages. Analyses of sequence-based secondary structure and the tertiary structure identify PPR as an intrinsically disordered region (IDR), implicating its role in regulation of replication. The identified propensity for the disorder-to-order state transitions indicates the PPR is involved in protein-protein interactions. Furthermore, the PPR of all four HEV genotypes contains seven putative linear binding motifs for ligands involved in the regulation of a wide number of cellular signaling processes. Structure-based analysis of possible molecular functions of these motifs showed the PPR is prone to bind a wide variety of ligands. Collectively, these data suggest a role for the PPR in HEV adaptation. Particularly as an IDR, the PPR likely contributes to fine tuning of viral replication through protein-protein interactions and should be considered as a target for development of novel anti-viral drugs