Implementation and Operational Research: An Integrated and Comprehensive Service Delivery Model to Improve Pediatric and Maternal HIV Care in Rural Africa.

BACKGROUND: Strategies to improve HIV diagnosis and linkage into care, antiretroviral treatment coverage, and treatment outcomes of mothers and children are urgently needed in sub-Saharan Africa. METHODS: From December 2012, we implemented an intervention package to improve prevention of mother-to-child transmission (PMTCT) and pediatric HIV care in our rural Tanzanian clinic, consisting of: (1) creation of a PMTCT and pediatric unit integrated within the reproductive and child health clinic; (2) implementation of electronic medical records; (3) provider-initiated HIV testing and counseling in the hospital wards; and (4) early infant diagnosis test performed locally. To assess the impact of this strategy, clinical characteristics and outcomes were compared between the period before (2008-2012) and during/after the implementation (2013-2014). RESULTS: After the intervention, the number of mothers and children enrolled into care almost doubled. Compared with the pre-intervention period (2008-2012), in 2013-2014, children presented lower CD4% (16 vs. 16.8, P = 0.08) and more advanced disease (World Health Organization stage 3/4 72% vs. 35%, P < 0.001). The antiretroviral treatment coverage rose from 80% to 98% (P < 0.001), the lost-to-follow-up rate decreased from 20% to 11% (P = 0.002), and mortality ascertainment improved. During 2013-2014, 261 HIV-exposed infants were enrolled, and the early mother-to-child transmission rate among mother-infant pairs accessing PMTCT was 2%. CONCLUSIONS: This strategy resulted in an increased number of mothers and children diagnosed and linked into care, a higher detection of children with AIDS, universal treatment coverage, lower loss to follow-up, and an early mother-to-child transmission rate below the threshold of elimination. This study documents a feasible and scalable model for family-centered HIV care in sub-Saharan Africa.

Gastrointestinal bleeding associated with rivaroxaban administration in a treated patient infected with human immunodeficiency virus.

The use of rivaroxaban in fixed dosing regimens without need for routine coagulation monitoring may lead to the misconception that there is a minimal risk of drug-drug interactions. We describe the case of a patient infected with human immunodeficiency virus (HIV) on salvage therapy who developed gastrointestinal bleeding while receiving the standard dose of rivaroxaban for the prevention of venous thromboembolism after surgery. This case clearly sends a warning that protease inhibitors should not be co-administered with rivaroxaban. Furthermore, it highlights the importance of clinicians' caution about potential drug-drug interactions.

Improved services to enrollees into an HIV rural care and treatment center in Tanzania.

Better quality of services is essential for the sustainability of HIV programs, in particular in rural Sub-Saharan Africa, to support the increasing number of individuals treated with combination antiretroviral therapy (cART). However, longitudinal data from rural care and treatment centers (CTC) are scarce. The objective was to assess trend in quality of care for HIV infected persons before start of combination antiretroviral therapy (pre-ART). A retrospective analysis of pre-ART registers and patient's files of 1950 patients enrolled in the Bagamoyo CTC in Tanzania between 2008 and 2010 analyzing was conducted; with parameters including year of enrollment, gender, age, CD4 cell count and WHO clinical stage at time enrollment. We noted a significant increase by 20% of total patients who had CD4 cell count performed from 69% (n=457) in 2008, 83% (n=493) 2009 to 89% (n=616) 2010 (X(2)= 87.014, P(2)= 14.945, P(2)= 85.028, P(3). Efforts must be undertaken for more HIV testing and timely referral of HIV-infected patients to CTC.

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals--the Swiss HIV Cohort Study.

BACKGROUND: Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. METHODS: Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5 log reduction). RESULTS: Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15). CONCLUSIONS: In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.

A longitudinal analysis of healthcare costs after treatment optimization following genotypic antiretroviral resistance testing: does resistance testing pay off?

OBJECTIVE: To assess the impact of antiretroviral therapy optimized by genotypic antiretroviral resistance testing (GRT) on healthcare costs over a 2-year period in patients after antiretroviral treatment failure. STUDY DESIGN: Non-randomized, prospective, tertiary care, clinic-based study. PATIENTS: One-hundred and forty-two HIV patients enrolled in the 'ZIEL' study and the Swiss HIV Cohort Study who experienced virological treatment failure. METHODS: For all patients GRT was used to optimize the antiretroviral treatment regimen. All healthcare costs during 2 years following GRT were assessed using microcosting. Costs were separated into ART medication costs and healthcare costs other than ART medication (that is, non-ART medication costs, in-patient costs and ambulatory [out-patient] costs). These cost estimates were then split into four consecutive 6-month periods (period 1-4) and the accumulated cost for each period was calculated. Univariate and multivariate regression modelling techniques for repeated measurements were applied to assess the changes of healthcare costs over time and factors associated with healthcare costs following GRT. RESULTS: Overall healthcare costs after GRT decreased over time and were significantly higher in period 1 (32%; 95% confidence interval [Cl]: 18-47) compared with period 4. ART medication costs significantly increased by 1,017 (95% Cl: 22-2,014) Swiss francs (CHF) from period 1-4, whereas healthcare costs other than ART medication costs decreased substantially by a factor of 3.1 (95% Cl: 2.6-3.7) from period 1 to period 4. Factors mostly influencing healthcare costs following GRT were AIDS status, costs being 15% (95% Cl: 6-24) higher in patients with AIDS compared with patients without AIDS, and baseline viral load, costs being 12% (95% Cl: 6-17) higher in patients with each log increase in plasma RNA. CONCLUSIONS: Optimized antiretroviral treatment regimens following GRT lead to a reduction of healthcare costs in patients with treatment failure over 2 years. Patients in a worse health state (that is, a positive AIDS status and high baseline viral load) will experience higher overall costs.

Dose-dependent influence of didanosine on immune recovery in HIV-infected patients treated with tenofovir.

BACKGROUND: Antiretroviral therapy (ART) containing tenofovir disoproxil fumarate (TDF) and didanosine (ddI) has been associated with poor immune recovery despite virologic success. This effect might be related to ddI toxicity since ddI exposure is substantially increased by TDF. OBJECTIVE: To analyze whether immune recovery during ART with TDF and ddI is ddI-dose dependent. DESIGN AND METHODS: A retrospective longitudinal analysis of immune recovery measured by the CD4 T-cell slope in 614 patients treated with ART containing TDF with or without ddI. Patients were stratified according to the tertiles of their weight-adjusted ddI dose: low dose (< 3.3 mg/kg), intermediate dose (3.3-4.1 mg/kg) and high dose (> 4.1 mg/kg). Cofactors modifying the degree of immune recovery after starting TDF-containing ART were identified by univariable and multivariable linear regression analyses. RESULTS: CD4 T-cell slopes were comparable between patients treated with TDF and a weight-adjusted ddI-dose of < 4.1 mg/kg per day (n = 143) versus TDF-without-ddI (n = 393). In the multivariable model the slopes differed by -13 CD4 T cells/mul per year [95% confidence interval (CI), -42 to 17; P = 0.40]. In contrast, patients treated with TDF and a higher ddI dose (> 4.1 mg/kg per day, n = 78) experienced a significantly impaired immune recovery (-47 CD4 T cells/microl per year; 95% CI, -82 to -12; P = 0.009). The virologic response was comparable between the different treatment groups. CONCLUSIONS: Immune recovery is impaired, when high doses of ddI (> 4.1 mg/kg) are given in combination with TDF. If the dose of ddI is adjusted to less than 4.1 mg/kg per day, immune recovery is similar to other TDF-containing ART regimen.