Challenges in management of Warfarin anti-coagulation in advanced HIV/AIDS patients with venous thrombotic events - A case series from a research clinic in rural Kericho, Kenya

Background: Venous thrombotic events (VTE) occur at high rates in HIV/AIDS patients and are likely under-diagnosed in rural sub-Saharan Africa.Objective: To describe clinical presentations and challenges in the management of VTE in patients with advanced HIV/AIDS.Design: Case series from patients enrolled in a prospective observational cohort study.Settings: A clinical research centre in rural Kericho, Kenya.Subjects: Two hundred patients with median age 38 (30-47) years, BMI 16.9 (12.4-20.3) kg/m2, haemoglobin 9.3 (6.8-13.4) g/dL, CD4+ T-cell count 27 (4-77) cells/mm3 and plasma HIV RNA 5.23 (3.70-5.88) log10copies/mL.Interventions: VTE cases were diagnosed by clinical presentation and Doppler/ radiographic confirmation.  Anti-coagulation therapy was managed by a multidisciplinary team; patients were initiated on enoxaparin or heparin followed by warfarin.Results: Over two years, 11 patients (5.5%) experienced VTE. All but one (10/11, 90.9%) case occurred within six months of starting ART. Nine patients had peripheral VTE (five popliteal, four femoral) and two had cerebral sinus thromboses. VTE was diagnosed 52 (1-469) days after ART initiation, and 81.8% of cases were outpatients at presentation. All patients received at least one concomitant medication that could significantly interact with warfarin (efavirenz, nevirapine, lopinavir/ritonavir, rifampicin, trimethoprim-sulfamethoxazole, and fluconazole). A median of 39 (10-180) days and eight (4-22) additional clinic visits were required to achieve/maintain a therapeutic INR of 2-3. Two minor bleeding complications occurred. No recurrent VTE cases were observed.Conclusion: Consideration of VTE and preparedness for management in patients with advanced HIV/AIDS starting ART is critical in sub-Saharan Africa. Overcoming challenges in anti-coagulation is possible in rural settings using a multidisciplinary team approach

The per-protocol effect of immediate versus deferred antiretroviral therapy initiation

OBJECTIVE: The START trial found a lower risk of a composite clinical outcome in HIV-positive individuals assigned to immediate initiation of antiretroviral therapy (ART) compared with those assigned to deferred initiation. However, 30% of those assigned to deferred initiation started ART earlier than the protocol specified. To supplement the published intention-to-treat effect estimates, here we estimate the per-protocol effect of immediate versus deferred ART initiation in START. DESIGN: The START trial randomized 4685 HIV-positive participants with CD4 counts > 500 /mm to start ART immediately after randomization (immediate initiation group) or to wait until the CD4 count dropped below 350 cells/mm or an AIDS diagnosis (deferred initiation group). METHODS: We used the parametric g-formula to estimate and compare the cumulative 5-year risk of the composite clinical outcome in the immediate and deferred initiation groups had all the trial participants adhered to the protocol. RESULTS: We estimated that the 5-year risk of the composite outcome would have been 3.2% under immediate ART initiation and 7.0% under deferred initiation. The difference of 3.8% (95% confidence interval 1.5,6.5) was larger than the intention-to-treat effect estimate of 3.1%, corresponding to a difference in effect estimates of 0.72% (-0.35,2.35). CONCLUSIONS: The intention-to-treat effect estimate may underestimate the benefit of immediate ART initiation by 23%. This estimate can be used by patients and policy makers who need to understand the full extent of the benefit of changes in ART initiation policies

Adult systemic cat scratch disease associated with therapy for hepatitis C

BACKGROUND: We describe the first case of systemic cat scratch disease in a patient receiving peginterferon α-2a and ribavirin for treatment of hepatitis C. Cases of adult systemic CSD are extremely infrequent and immunomodulatory treatment for hepatitis C has been associated with aberrant host responses to common pathogens. CASE PRESENTATION: A 52 year old man being treated for hepatitis C presented with diffuse lymphadenopathy, weight loss, fevers and splenic lesions. Symptoms were initially confused with adverse effects of his regimen, delaying recognition of his infection. Diagnostic investigation, including histopathology, microbiology and serologic parameters, confirmed that his illness was due to disseminated cat scratch disease with Bartonella henselae. CONCLUSION: Disseminated CSD is exceptionally rare in adults. We describe the first case of disseminated cat scratch disease associated with peginterferon α and ribavirin to alert clinicians of the need to be aware of unusual manifestations of common infections in this population

Using Veterans Affairs Medical Center (VAMC) data to identify missed opportunities for HPV vaccination

Despite high HPV prevalence and low vaccination rates in the military, HPV vaccination is not required upon military service initiation. Given that national HPV vaccination rates remain low among people age 19–26 years, military service may represent an opportune time for intervention. The purpose of this study was to quantify the rate of HPV vaccination among young patients entering primary care at a single Veterans Affairs Medical Center (VAMC). Vaccination rates among veterans age ≤ 26 years old at first primary care visit were identified from the institutional data warehouse. Among 1,258 eligible patients, most were male (n = 782). The HPV vaccine initiation rate was 21.2%. Overall, 10.4% of patients received at least 1 HPV vaccine prior to initiating care at the VA (25.2% females and 1.4% males). An additional 10.8% of patients received their first HPV vaccine upon initiating care at the VA. Median age of first HPV vaccination was 21.4 years among patients that initiated the vaccine in the military versus 24.8 years among those that initiated vaccination at the VA. In conclusion, this study demonstrated low HPV vaccination rates both prior to transitioning to VA primary care and once receiving care at the VA. Additionally, among veterans that had not received vaccination upon initiating care at the VA, older age at vaccination was observed. Older age at vaccination may reduce HPV vaccine effectiveness given higher risk of exposure. Addition of HPV to the list of mandated vaccines upon military service initiation should be considered

The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility

Segmental duplications in the human genome are selectively enriched for genes involved in immunity, although the phenotypic consequences for host defense are unknown. We show that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1 (MIP-1alphaP), a potent human immunodeficiency virus-1 (HIV-1)-suppressive chemokine and ligand for the HIV coreceptor CCR5. Possession of a CCL3L1 copy number lower than the population average is associated with markedly enhanced HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This susceptibility is even greater in individuals who also possess disease-accelerating CCR5 genotypes. This relationship between CCL3L1 dose and altered HIV/AIDS susceptibility points to a central role for CCL3L1 in HIV/AIDS pathogenesis and indicates that differences in the dose of immune response genes may constitute a genetic basis for variable responses to infectious diseases