Sarah E. Rutstein

Role of acute and early HIV infection in the sexual transmission of HIV.

Purpose of reviewAcute HIV infection (AHI), the earliest period after HIV acquisition, is only a few weeks in duration. In this brief period, the concentration of HIV in blood and genital secretions is extremely high, increasing the probability of HIV transmission. Although a substantial role of AHI in the sexual transmission of HIV is biologically plausible, the significance of AHI in the epidemiological spread of HIV remains uncertain. Recent findingsAHI is diagnosed by detecting viral RNA or antigen in the blood of persons who are HIV seronegative. Depending on the setting, persons with AHI represent between 1 and 10% of persons with newly diagnosed HIV infection. The high concentration of virus during AHI leads to increased infectiousness, possibly as much as 26 times greater than during chronic infection. In mathematical models, the estimated proportion of transmission attributed to AHI has varied considerably, depending on model structure, model parameters, and the population. Key determinants include the stage of the HIV epidemic and the sexual risk profile of the population. SummaryDespite its brief duration, AHI plays a disproportionate role in the sexual transmission of HIV infection. Detection of persons with AHI may provide an important opportunity for transmission prevention.

Detection of Acute HIV Infection: A Field Evaluation of the Determine® HIV-1/2 Ag/Ab Combo Test

BACKGROUND Most human immunodeficiency virus (HIV) point-of-care tests detect antibodies (Ab) but not p24 antigen (Ag) or RNA. In the absence of antibodies, p24 antigen and RNA typically indicate acute HIV infection. We conducted a field evaluation of the Determine® HIV-1/2 Ag/Ab Combo rapid test (Combo RT). METHODS The antigen portion of the Combo RT (for acute HIV infection) was compared with a Roche Monitor HIV RNA polymerase chain reaction assay. The antibody portion of Combo RT (for established HIV infection) was compared with rapid test algorithms. Participants were enrolled at a sexually transmitted infection clinic and HIV testing and counseling center in Lilongwe, Malawi. Rapid testing was conducted with parallel testing in the clinic and serial testing in the center. The Combo RT was performed in clinic participants with negative or discordant antibody results and in all center participants. RESULTS Of the participants 838 were HIV negative, 163 had established HIV infection, and 8 had acute HIV infection. For detecting acute HIV infection, the antigen portion had a sensitivity of 0.000 and a specificity of 0.983. For detecting established HIV infection, the antibody portion had a sensitivity of 0.994 and a specificity of 0.992. CONCLUSIONS Combo RT displayed excellent performance for detecting established HIV infection and poor performance for detecting acute HIV infection. In this setting, Combo RT is no more useful than current algorithms.

The detection and management of early HIV infection: A clinical and public health emergency

Abstract:This review considers the detection and management of early HIV infection (EHI), defined here as the first 6 months of infection. This phase is clinically important because a reservoir of infected cells formed in the individual renders HIV incurable, and the magnitude of viremia at the end of this period predicts the natural history of disease. Epidemiologically, it is critical because the very high viral load that typically accompanies early infection also makes infected individuals maximally contagious to their sexual partners. Future efforts to prevent HIV transmission with expanded testing and treatment may be compromised by elevated transmission risk earlier in the course of HIV infection, although the extent of this impact is yet unknown. Treatment as prevention efforts will nevertheless need to develop strategies to address testing, linkage to care, and treatment of EHI. Cost-effective and efficient identification of more persons with early HIV will depend on advancements in diagnostic technology and strengthened symptom-based screening strategies. Treatment for persons with EHI must balance individual health benefits and reduction of the risk of onward viral transmission. An increasing body of evidence supports the use of immediate antiretroviral therapy to treat EHI to maintain CD4 count and functionality, limit the size of the HIV reservoir, and reduce the risk of onward viral transmission. Although we can anticipate considerable challenges in identifying and linking to care persons in the earliest phases of HIV infection, there are many reasons to pursue this strategy.

On the front line of HIV virological monitoring: barriers and facilitators from a provider perspective in resource-limited settings

Scale-up of viral load (VL) monitoring for HIV-infected patients on antiretroviral therapy (ART) is a priority in many resource-limited settings, and ART providers are critical to effective program implementation. We explored provider-perceived barriers and facilitators of VL monitoring. We interviewed all providers (n = 17) engaged in a public health evaluation of dried blood spots for VL monitoring at five ART clinics in Malawi. All ART clinics were housed within district hospitals. We grouped themes at patient, provider, facility, system, and policy levels. Providers emphasized their desire for improved ART monitoring strategies, and frustration in response to restrictive policies for determining which patients were eligible to receive VL monitoring. Although many providers pled for expansion of monitoring to include all persons on ART, regardless of time on ART, the most salient provider-perceived barrier to VL monitoring implementation was the pressure of work associated with monitoring activities. The work burden was exacerbated by inefficient data management systems, highlighting a critical interaction between provider-, facility-, and system-level factors. Lack of integration between laboratory and clinical systems complicated the process for alerting providers when results were available, and these communication gaps were intensified by poor facility connectivity. Centralized second-line ART distribution was also noted as a barrier: providers reported that the time and expenses required for patients to collect second-line ART frequently obstructed referral. However, provider empowerment emerged as an unexpected facilitator of VL monitoring. For many providers, this was the first time they used an objective marker of ART response to guide clinical management. Providers’ knowledge of a patients virological status increased confidence in adherence counseling and clinical decision-making. Results from our study provide unique insight into provider perceptions of VL monitoring and indicate the importance of policies responsive to individual and environmental challenges of VL monitoring program implementation. Findings may inform scale-up by helping policy-makers identify strategies to improve feasibility and sustainability of VL monitoring.

Measures of viral load using Abbott RealTime HIV-1 Assay on venous and fingerstick dried blood spots from provider-collected specimens in Malawian District Hospitals

BACKGROUND Viral suppression is a key indicator of antiretroviral therapy (ART) response among HIV-infected patients. Dried blood spots (DBS) are an appealing alternative to conventional plasma-based virologic testing, improving access to monitoring in resource-limited settings. However, validity of DBS obtained from fingerstick in field settings remains unknown. OBJECTIVES Investigate feasibility and accuracy of DBS vs plasma collected by healthcare workers in real-world settings of remote hospitals in Malawi. Compare venous DBS to fingerstick DBS for identifying treatment failure. STUDY DESIGN We recruited patients from ART clinics at two district hospitals in Malawi, collecting plasma, venous DBS (vDBS), and fingerstick DBS (fsDBS) cards for the first 149 patients, and vDBS and fsDBS only for the subsequent 398 patients. Specimens were tested using Abbott RealTime HIV-1 Assay (lower detection limit 40 copies/ml (plasma) and 550 copies/ml (DBS)). RESULTS 21/149 (14.1%) had detectable viremia (>1.6 log copies/ml), 13 of which were detectable for plasma, vDBS, and fsDBS. Linear regression demonstrated high correlation for plasma vs. DBS (vDBS: β=1.19, R(2)=0.93 (p<0.0001); fsDBS β=1.20, R(2)=0.90 (p<0.0001)) and vDBS vs. fsDBS (β=0.88, R(2)=0.73, (p<0.0001)). Mean difference between plasma and vDBS was 1.1 log copies/ml [SD: 0.27] and plasma and fsDBS 1.1 log copies/ml [SD: 0.31]. At 5000 copies/ml, sensitivity was 100%, and specificity was 98.6% and 97.8% for vDBS and fsDBS, respectively, compared to plasma. CONCLUSIONS DBS from venipuncture and fingerstick perform well at the failure threshold of 5000 copies/ml. Fingerstick specimen source may improve access to virologic treatment monitoring in resource-limited settings given task-shifting in high-volume, low-resource facilities.

Dried blood spots for viral load monitoring in Malawi: feasible and effective.

Objectives To evaluate the feasibility and effectiveness of dried blood spots (DBS) use for viral load (VL) monitoring, describing patient outcomes and programmatic challenges that are relevant for DBS implementation in sub-Saharan Africa. Methods We recruited adult antiretroviral therapy (ART) patients from five district hospitals in Malawi. Eligibility reflected anticipated Ministry of Health VL monitoring criteria. Testing was conducted at a central laboratory. Virological failure was defined as >5000 copies/ml. Primary outcomes were program feasibility (timely result availability and patient receipt) and effectiveness (second-line therapy initiation). Results We enrolled 1,498 participants; 5.9% were failing at baseline. Median time from enrollment to receipt of results was 42 days; 79.6% of participants received results within 3 months. Among participants with confirmed elevated VL, 92.6% initiated second-line therapy; 90.7% were switched within 365 days of VL testing. Nearly one-third (30.8%) of participants with elevated baseline VL had suppressed (<5,000 copies/ml) on confirmatory testing. Median period between enrollment and specimen testing was 23 days. Adjusting for relevant covariates, participants on ART >4 years were more likely to be failing than participants on therapy 1–4 years (RR 1.7, 95% CI 1.0-2.8); older participants were less likely to be failing (RR 0.95, 95% CI 0.92-0.98). There was no difference in likelihood of failure based on clinical symptoms (RR 1.17, 95% CI 0.65-2.11). Conclusions DBS for VL monitoring is feasible and effective in real-world clinical settings. Centralized DBS testing may increase access to VL monitoring in remote settings. Programmatic outcomes are encouraging, especially proportion of eligible participants switched to second-line therapy.

A preoperative personalized risk assessment calculator for elderly ovarian cancer patients undergoing primary cytoreductive surgery

OBJECTIVE Cytoreductive surgery for ovarian cancer has higher rates of postoperative complication than neoadjuvant chemotherapy followed by surgery. If patients at high risk of postoperative complication were identified preoperatively, primary therapy could be tailored. Our objective was to develop a predictive model to estimate the risk of major postoperative complication after primary cytoreductive surgery among elderly ovarian cancer patients. METHODS Patients who underwent primary surgery for ovarian cancer between 2005 and 2013 were identified from the National Surgical Quality Improvement Project. Patients were selected using primary procedure CPT codes. Major complications were defined as grade 3 or higher complications on the validated Claviden-Dindo scale. Using logistic regression, we identified demographic and clinical characteristics predictive of postoperative complication. RESULTS We identified 2101 ovarian cancer patients of whom 35.9% were older than 65. Among women older than 65, the rate of major postoperative complication was 16.4%. Complications were directly associated with preoperative laboratory values (serum creatinine, platelets, white blood cell count, hematocrit), ascites, white race, and smoking status, and indirectly associated with albumin. Our predictive model had an area under receiver operating characteristic curve of 0.725. In order to not deny patients necessary surgery, we chose a 50% population rate of postoperative complication which produced model sensitivity of 9.8% and specificity of 98%. DISCUSSION Our predictive model uses easily and routinely obtained objective preoperative factors to estimate the risk of postoperative complication among elderly ovarian cancer patients. This information can be used to assess risk, manage postoperative expectations, and make decisions regarding initial treatment.

Laparoscopic hysterectomy with morcellation vs abdominal hysterectomy for presumed fibroids: an updated decision analysis following the 2014 Food and Drug Administration safety communications

&NA; Previous decision analyses demonstrate the safety of minimally invasive hysterectomy for presumed benign fibroids, accounting for the risk of occult leiomyosarcoma and the differential mortality risk associated with laparotomy. Studies published since the 2014 Food and Drug Administration safety communications offer updated leiomyosarcoma incidence estimates. Incorporating these studies suggests that mortality rates are low following hysterectomy for presumed benign fibroids overall, and a minimally invasive approach remains a safe option. Risk associated with morcellation, however, increases in women age >50 years due to increased leiomyosarcoma rates, an important finding for patient‐centered discussions of treatment options for fibroids.

Clinical and public health implications of acute and early HIV detection and treatment: a scoping review

Introduction: The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI.

STI Patients Are Effective Recruiters of Undiagnosed Cases of HIV: Results of a Social Contact Recruitment Study in Malawi

Background:Patients with newly diagnosed HIV may be part of social networks with elevated prevalence of undiagnosed HIV infection. Social network recruitment by persons with newly diagnosed HIV may efficiently identify undiagnosed cases of HIV infection. We assessed social network recruitment as a strategy for identifying undiagnosed cases of HIV infection. Methods:In a sexually transmitted infection (STI) clinic in Lilongwe, Malawi, 3 groups of 45 “seeds” were enrolled: STI patients with newly diagnosed HIV, STI patients who were HIV-uninfected, and community controls. Seeds were asked to recruit up to 5 social “contacts” (sexual or nonsexual). Mean number of contacts recruited per group was calculated. HIV prevalence ratios (PRs) and number of contacts needed to test to identify 1 new case of HIV were compared between groups using generalized estimating equations with exchangeable correlation matrices. Results:Mean number of contacts recruited was 1.3 for HIV-infected clinic seeds, 1.8 for HIV-uninfected clinic seeds, and 2.3 for community seeds. Contacts of HIV-infected clinic seeds had a higher HIV prevalence (PR: 3.2, 95% confidence interval: 1.3 to 7.8) than contacts of community seeds, but contacts of HIV-uninfected clinic seeds did not (PR: 1.1, 95% confidence interval: 0.4 to 3.3). Results were similar when restricted to nonsexual contacts. To identify 1 new case of HIV, it was necessary to test 8 contacts of HIV-infected clinic seeds, 10 contacts of HIV-uninfected clinic seeds, and 18 contacts of community seeds. Conclusions:Social contact recruitment by newly diagnosed STI patients efficiently led to new HIV diagnoses. Research to replicate findings and guide implementation is needed.