Regression discontinuity analysis demonstrated varied effect of Treat-All on CD4 testing among Southern African countries.

OBJECTIVE: To determine whether Treat-All policy impacted laboratory testing practices of antiretroviral therapy (ART) programs in Southern Africa. STUDY DESIGN AND SETTING: We used HIV cohort data from Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in a regression discontinuity design to estimate changes in pre-ART CD4 testing and viral load monitoring following national Treat-all adoption that occurred during 2016 to 2017. This study included more than 230,000 ART-naïve people living with HIV (PLHIV) aged five years or older who started ART within two years of national Treat-All adoption. RESULTS: We found pre-ART CD4 testing decreased following adoption of Treat-All recommendations in Malawi (-21.4 percentage points (pp), 95% confidence interval, CI: -26.8, -16.0) and in Mozambique (-8.8pp, 95% CI: -14.9, -2.8), but increased in Zambia (+2.7pp, 95% CI: +0.4, +5.1). Treat-All policy had no effect on viral load monitoring, except among females in South Africa (+7.1pp, 95% CI: +1.1, +13.0). CONCLUSION: Treat-All policy expanded ART eligibility, but led to reductions in pre-ART CD4 testing in some countries that may weaken advanced HIV disease management. Continued and expanded support of CD4 and viral load laboratory capacity is needed to further improve treatment successes and allow for uniform evaluation of ART implementation across Southern Africa.

Assessment of two POC technologies for CD4 count in Morocco.

BACKGROUND: In the era of "test and treat strategy", CD4 testing remains an important tool for monitoring HIV-infected individuals. Since conventional methods of CD4 count measurement are costly and cumbersome, POC CD4 counting technique are more affordable and practical for countries with limited resources. Before introducing such methods in Morocco, we decided to assess their reliability. METHODS: In this study 92 blood samples from HIV-infected patients, were tested by PIMA and FACSPresto to derive CD4 count. Flow cytometry using FacsCalibur, was used as reference method for CD4 count comparison. Linear regression, Bland-Altman analysis were performed to assess correlation and agreement between these POC methods and the reference method. In addition, sensitivity and specificity, positive predictive value (PPV), negative predictive value (NPV) and misclassification percentage at 350 and 200 CD4 count thresholds; were also determined. Finally, because FACSPresto can also measure hemoglobin (Hb) concentration, 52 samples were used to compare FACSPresto against an automated hematology analyzer. RESULTS: The coefficient of determination R2 was 0.93 for both methods. Bland-Altman analysis displayed a mean bias of - 32.3 and - 8.1 cells/µl for PIMA and FACSPresto, respectively. Moreover, with a threshold of 350 CD4 count, PIMA displayed a sensitivity, specificity, PPV, NPV, were 88.57%, 94.12%, 91.18%, 92.31%; respectively. FACSPresto showed 88.23%, 96.23%, 93.75% and 92.73%; respectively. Furthermore, the upward misclassification percentage was 8.57 and 5.88%, for PIMA and FACSPresto, respectively; whereas the downward misclassification percentage was 7.84% and 7.54%; respectively. With 200 cells/µl threshold, PIMA had a sensitivity, specificity, PPV and NPV of 83.33%, 98.53%, 93.75% and 95.71%, respectively. Regarding FACSPresto, sensitivity, specificity, PPV and NPV was 82.35%, 98.57%, 88.57% and 95.83%; respectively. Upward misclassification percentage was 5.56% and 5.88%, for PIMA and FACSPresto, respectively; whereas downward misclassification percentage was 4.41% and 4.29%; respectively. Finally, the hemoglobin measurement evaluation displayed an R2 of 0.80 and a mean bias of - 0.12 with a LOA between - 1.75 and 1.51. CONCLUSION: When compared to the reference method, PIMA and FACSPresto have shown good performance, for CD4 counting. The introduction of such POC technology will speed up the uptake of patients in the continuum of HIV care, in our country.

Magnitude of Anemia and Associated Factors Among Human Immunodeficiency Virus Infected Children on Highly Active Antiretroviral Therapy at University of Gondar Comprehensive and Specialized Referral Hospital Northwest Ethiopia.

BACKGROUND: Anemia is one of the most common hematological problems in HIV infected patients in the world. The main aim of this study was to determine the magnitude of anemia and associated factors among HIV infected children on highly active antiretroviral therapy attending University of Gondar Comprehensive and Specialized Referral Hospital. METHODS: A retrospective study was conducted from 2013 to 2018 by reviewing medical records at University of Gondar Comprehensive and Specialized Referral Hospital ART clinic. Records of 238 HIV infected children on HAART were selected using a convenient sampling technique. Socio-demographic characteristics, clinical information, and hematological and immunological profiles of the study participants were collected from the patients record books. WHO cutoff value of hemoglobin was taken and adjusted to define anemia in higher altitude. Data was analyzed by using the SPSS version 20 statistical software, and odds ratios with 95% confidence intervals were used to quantify the strength of association between anemia and its potential predictors. RESULTS: The overall prevalence of anemia among HIV infected children in this study was 38.7%. Of anemic children, 48.9% had mild, 39.1% moderate, and 11.9% severe anemia. This study showed that HIV infected children on Highly Active Antiretroviral Therapy who live in rural residence had a two-fold risk of being anemia than urban dwellers (AOR = 2.151, 95% CI, 1.123 - 4.122). There was no significant association with gender, WHO clinical stage, opportunistic infections, cotrimoxazole treatment, and CD4 count percentage. CONCLUSIONS: Anemia is a common problem among the children taking highly active antiretroviral therapy. Therefore, health care workers need to routinely investigate and treat anemia, especially in rural dwellers. Furthermore, large scale and longitudinal studies are recommended to strengthen and explore the problem in depth.

Development of a multiplex fully automated assay for rapid quantification of CD4+ T cells from whole blood.

The development of cost-effective and rapid assays for the accurate counting of CD4 cells has remained prime focus for disease management. The lack of such assays has severely affected people living in resource-limited disease prevalent areas. CD4 count information plays a vital role in the effective management of HIV disease. There is an unmet need to develop rapid, cost-effective, portable and user-friendly point-of-care (POC) disease diagnostic platform technology for CD4+ T cell counting. Here, we have developed a flow-free magnetic actuation platform that uses antibody-coated magnetic beads to efficiently capture CD4+ T cells from a 30 µL drop of whole blood. On-chip cell lysate electrical impedance spectroscopy has been utilized to quantify the isolated CD4 cells. The developed assay has a limit of detection of 25 cells per µL and provides accurate CD4 counts in the range of 25-800 cells per µL. The whole immunoassay along with the enumeration process is very rapid and provides CD4 quantification results within 5 min time frame. The assay does not require off-chip sample preparation steps and minimizes human involvement to a greater extent. The developed impedance-based immunoassay has potential to significantly improve the CD4 enumeration process especially for POC settings.

A Rapid, Simple, and Low-Cost CD4 Cell Count Sensor Based on Blocking Immunochromatographic Strip System.

The counting of CD4+ T lymphocytes (CD4 cells) is a critical test for evaluating the immune function of HIV-infected peoples and tumor patients. A rapid, simple, accurate, and low-cost CD4 cell counting method as a diagnostic tool is increasingly required in the clinic. We designed and developed a novel fluorescent immunochromatographic strips (ICS) system based on the blocking principle for counting CD4 cells. The strategy of this system is to count CD4 cells indirectly, by measuring the free CD4 antibodies that were not bound by CD4 cells. The fluorescent antibodies bound to CD4 cells were blocked at the filter pads, resulting in a decrease in fluorescence of free CD4 antibodies measured. The number of CD4 cells was inversely related to the fluorescence intensity. The CD4 count-ICSs exhibited a quasilinear response ( R2 = 0.96) to logarithmic CD4 cell concentrations in PBMC samples in the range of 50-1000 cells/µL. In addition, the CD4 count-ICSs reliably quantified CD4 cells in whole blood samples, where the assay exhibited a linear correlation ( R2 = 0.976) readout for CD4 cell concentrations ranging from 100 to 800 cells/µL. To validate the clinical applicability of this method, 54 blood samples were measured: the detection results showed a high correlation ( R2 > 0.97) with the flow cytometry (FCM) analysis. The fluorescent ICSs can be used to count CD4 cells in blood samples, which have a high coincidence rate with FCM analysis; therefore, the CD4 count ICS system is an excellent candidate method for CD4 cell counting in resource-limited settings.

Field Performance and Diagnostic Accuracy of a Low-Cost Instrument-Free Point-of-Care CD4 Test (Visitect CD4) Performed by Different Health Worker Cadres among Pregnant Women.

Measuring CD4 counts remains an important component of HIV care. The Visitect CD4 is the first instrument-free low-cost point-of-care CD4 test with results interpreted visually after 40 min, providing a result of ≥350 CD4 cells/mm3 The field performance and diagnostic accuracy of the test was assessed among HIV-infected pregnant women in South Africa. A nurse performed testing at the point-of-care using both venous and finger-prick blood, and a counselor and laboratory staff tested venous blood in the clinic laboratory (four Visitect CD4 tests/participant). Performance was compared to the mean CD4 count from duplicate flow cytometry tests on venous blood (FACSCalibur Trucount). In 2017, 156 patients were enrolled, providing a total of 624 Visitect CD4 tests (468 venous and 156 finger-prick samples). Of 624 tests, 28 (4.5%) were inconclusive. Generalized linear mixed modeling showed better performance of the test on venous blood (sensitivity = 81.7%; 95% confidence interval [CI] = 72.3 to 91.1]; specificity = 82.6%, 95% CI = 77.1 to 88.1) than on finger-prick specimens (sensitivity = 60.7%; 95% CI = 45.0 to 76.3; specificity = 89.5%, 95% CI = 83.2 to 95.8; P = 0.001). No difference in performance was detected by cadre of health worker (P = 0.113) or between point-of-care versus laboratory-based testing (P = 0.108). Adequate performance of Visitect CD4 with different operators and at the point of care, with no need of electricity or instrument, shows the potential utility of this device, especially for facilitating decentralization of CD4 testing services in rural areas.

Enhancing value and lowering costs of care: a qualitative exploration of a randomized linkage to care intervention in South Africa.

While interventions to improve HIV linkage and retention in care exist, none have demonstrated results sufficient to reach UNAIDS 90-90-90 goals. We explored values and costs of seeking clinical care through testing three strategies to improve linkage to care: Point of care CD4 testing alone (POC-CD4), POC-CD4 combined with transportation support and combined with care facilitation. We conducted in-depth interviews with participants and transcribed audio-recordings of care facilitation sessions. Participants described values and costs enhanced or addressed by the three interventions. Psychosocial support provided through the care facilitation intervention appeared salient. Participants named other values and costs of seeking care unrelated to the intervention, such as encouragement from healthcare workers and aversion to lifelong treatment. Combined with the quantitative results of this trial, these findings may point to why the care facilitation arm was successful but not the POC-CD4 only or transportation arms. It also provides guidance for future interventions.

Epidemiology and clinical management of HIV-HBV coinfected patients in a large AIDS Reference Center in Belgium.

Objectives: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are both worldwide health concerns with similar routes of transmission and no curative treatment to date. Coinfection is associated with increased morbidity and mortality. We aim to provide epidemiological data about HIV-HBV coinfected patients and asses if management of patients following European recommendation (EACS) was achieved in a large AIDS Reference Center in Belgium. Methods: Retrospective review of the HIV database of Saint-Pierre University Hospital in Brussels (Belgium) focusing on HIV-HBV coinfected patients in active follow-up. We classified patients in six serological profiles: (A) patients with active chronic HBV infection (HBsAg positive and HBeAg positive), (B) patients with persistent chronic HBV infection (HBsAg positive and HBeAg negative), (C) patients with isolated core antibody (isolated anti-HBc positive), (D) patients with resolved HBV infection (anti-HBc positive and anti-HBs positive), (E) vaccinated patients (anti-HBs positive), and (F) patients with all above markers negative. Chronic HBV infection (cHBV) was defined by two positive hepatitis B surface antigens (AgHBs positive) with at least 6-month intervals and chronic HBeAg positive group by a positive AgHBe (Ag HBe positive). We reviewed individual files of HIV-HBV chronically coinfected patients to assess if European recommendations in terms of HBV coinfection management were adequately followed in our center. Results: Among 2601 HIV-infected patients in active follow-up, 98 (3.8%) were chronically infected with HBV. Median age of chronically coinfected patients was 46 years with male predominance and heterosexual Africans representing the majority. Among the chronically coinfected patients, 33.7% were HBeAg positive carriers. Mean HBV DNA and ALT/AST were significantly higher in the chronic HBeAg positive (cHBeAg positive) patients compared to chronic HBeAg negative patients (cHBeAg negative). Nearly 95% of the cHBV patients were treated with two anti-HBV drugs (99% for the cHBeAg positive group), with 79% having Tenofovir (TDF) in their antiretroviral treatment history. 8% were screened for hepatitis D virus (HDV) antibodies. Liver fibrosis, upper endoscopy and alpha-foetoprotein were assessed at least once in the last 5 years in 32%, 31% and 32% of cHBV patients respectively. cHBeAg positive patients were not significantly monitored closer except for liver fibrosis assessment in 52% (p < 0.0017). Conclusion: The prevalence of cHBV coinfection in the Saint-Pierre HIV cohort is lower than in neighboring European countries. Hepatic monitoring should be reinforced in our cHBV and cHBeAg positive patients because of higher risk of progression to cirrhosis progression and hepatocellular carcinoma.

Cost-Effectiveness Analysis of Early vs Late Diagnosis of HIV-Infected Patients in South Carolina.

OBJECTIVES: It is anticipated that early diagnosis, linkage to care, initiation of antiretroviral therapy (ART), and retention in care would lead to reduced opportunistic infections, reduction in human immunodeficiency virus-related morbidity and mortality and reduced rates of HIV transmission. This would be expected to lead to a reduction in the lifetime cost of care (LCC). This study analyzed existing data to determine to what extent early-versus-late HIV diagnosis affects LCC. METHODS: The South Carolina Department of Health and Environmental Control electronic HIV/acquired immunodeficiency syndrome reporting system data were used for this study. The first CD4 and viral load reported to the Enhanced HIV/AIDS Reporting System of the Centers for Disease Control and Prevention are considered the initial CD4 and viral load. Late HIV diagnosis was based on a CD4 count ≤200 at diagnosis. A previously validated simulation model developed by the John Snow Institute for the South Carolina Department of Health and Environmental Control was used to determine the discounted LCC. Comparisons were made between late and early HIV diagnosis. RESULTS: From 2013 through 2015, 2138 individuals were diagnosed as having HIV in South Carolina; 180 individuals were excluded from further analysis because an initial CD4 count was missing. Final analysis was based on 1958 individuals. Late HIV diagnosis occurred in 509 individuals (26%). When stratified based on CD4 count at diagnosis, the discounted LCC per person in those with an initial CD4 count ≤200 was $262,374 and in those with an initial CD4 count >500 was $416,766. Those with lower CD4 counts at diagnosis had more lost quality-adjusted life-years (QALYs; 7.95 QALYs lost per person with an initial CD4 count ≤200 compared with 4.45 QALYs lost per person with an initial CD4 count >500), more lifetime HIV transmissions (1.4 per person with an initial CD4 count ≤200 compared with 0.72 per person with an initial CD4 count >500), and lower additional life expectancy (30.73 additional years with an initial CD4 count ≤200 compared with 38.08 additional years with an initial CD4 count >500). CONCLUSIONS: Although individuals with lower CD4 counts at diagnosis had a lower discounted LCC, they had more lost QALYs, more lifetime HIV transmissions, and lower additional life expectancy.

Visceral Leishmaniasis and HIV Co-Infection in Northwest Ethiopia: Antiretroviral Treatment and Burden of Disease among Patients Enrolled in HIV Care.

The approach to treatment of visceral leishmaniasis (VL)-HIV co-infection in East Africa has not been systematically examined. Although antiretroviral treatment (ART) should be initiated for all co-infected persons, the extent of ART prescription is not known. We conducted a retrospective cohort study including all VL-HIV co-infected adults at selected referral and district hospitals in northwest Ethiopia from 2010 to 2015. Purposes of the study were to compare the proportion of VL diagnoses made in previously diagnosed HIV-patients versus diagnosis concurrent with HIV diagnosis and to quantify utilization of ART. We included 112 patients and 58 patients at the referral and district hospital, respectively (median age: 30 years, 98% males). Of all VL cases, 56% (63/112) and 19% (11/58) occurred in known HIV patients at the referral and district hospital, respectively, with a median CD4 count at VL diagnosis of 45 cells/µL and 248 cells/µL at the referral and district hospital, respectively. Seventy-six percent (56/44) were on ART at VL diagnosis and nine (12%) started ART after VL diagnosis. The remaining 96 (56%) patients had both infections diagnosed concurrently, with a median CD4 count of 56 and 143 cells/µL at the referral and district hospital, respectively. Among cured patients, ART initiation was 67% and 36% at the referral and district hospital, respectively. A substantial proportion of VL-HIV cases occur while in HIV care, requiring further evaluation of preventive strategies. Among newly diagnosed VL-HIV co-infected patients, ART initiation was low. The reasons, including poor documentation and information exchange, should be assessed.

Prevalence and predictors of late presentation for HIV care in South Africa.

BACKGROUND: Many people living with HIV in South Africa (SA) are not aware of their seropositive status and are diagnosed late during the course of HIV infection. These individuals do not obtain the full benefit from available HIV care and treatment services. OBJECTIVES: To describe the prevalence of late presentation for HIV care among newly diagnosed HIV-positive individuals and evaluate sociodemographic variables associated with late presentation for HIV care in three high-burden districts of SA. METHODS: We used data abstracted from records of 8 138 newly diagnosed HIV-positive individuals in 35 clinics between 1 June 2014 and 31 March 2015 to determine the prevalence of late presentation among newly diagnosed HIV-positive individuals in selected high-prevalence health districts. Individuals were categorised as 'moderately late', 'very late' or 'extremely late' presenters based on specified criteria. Descriptive analysis was performed to measure the prevalence of late presentation, and multivariate regression analysis was conducted to identify variables independently associated with extremely late presentation. RESULTS: Overall, 79% of the newly diagnosed cases presented for HIV care late in the course of HIV infection (CD4+ count ≤500 cells/µL and/or AIDS-defining illness in World Health Organization (WHO) stage III/IV), 19% presented moderately late (CD4+ count 351 - 500 cells/µL and WHO clinical stage I or II), 27% presented very late (CD4+ count 201 - 350 cells/µL or WHO clinical stage III), and 33% presented extremely late (CD4+ count ≤200 cells/µL and/or WHO clinical stage IV) for HIV care. Multivariate regression analysis indicated that males, non-pregnant women, individuals aged >30 years, and those accessing care in facilities located in townships and inner cities were more likely to present late for HIV care. CONCLUSIONS: The majority of newly diagnosed HIV-positive individuals in the three high-burden districts (Gert Sibande, uThukela and City of Johannesburg) presented for HIV care late in the course of HIV infection. Interventions that encourage early presentation for HIV care should be prioritised in SA and should target males, non-pregnant women, individuals aged >30 years and those accessing care in facilities located in inner cities and urban townships.

The value of point-of-care CD4+ and laboratory viral load in tailoring antiretroviral therapy monitoring strategies to resource limitations.

OBJECTIVE: To examine the clinical and economic value of point-of-care CD4 (POC-CD4) or viral load monitoring compared with current practices in Mozambique, a country representative of the diverse resource limitations encountered by HIV treatment programs in sub-Saharan Africa. DESIGN/METHODS: We use the Cost-Effectiveness of Preventing AIDS Complications-International model to examine the clinical impact, cost (2014 US$), and incremental cost-effectiveness ratio [$/year of life saved (YLS)] of ART monitoring strategies in Mozambique. We compare: monitoring for clinical disease progression [clinical ART monitoring strategy (CLIN)] vs. annual POC-CD4 in rural settings without laboratory services and biannual laboratory CD4 (LAB-CD4), biannual POC-CD4, and annual viral load in urban settings with laboratory services. We examine the impact of a range of values in sensitivity analyses, using Mozambique's 2014 per capita gross domestic product ($620) as a benchmark cost-effectiveness threshold. RESULTS: In rural settings, annual POC-CD4 compared to CLIN improves life expectancy by 2.8 years, reduces time on failed ART by 0.6 years, and yields an incremental cost-effectiveness ratio of $480/YLS. In urban settings, biannual POC-CD4 is more expensive and less effective than viral load. Compared to biannual LAB-CD4, viral load improves life expectancy by 0.6 years, reduces time on failed ART by 1.0 year, and is cost-effective ($440/YLS). CONCLUSION: In rural settings, annual POC-CD4 improves clinical outcomes and is cost-effective compared to CLIN. In urban settings, viral load has the greatest clinical benefit and is cost-effective compared to biannual POC-CD4 or LAB-CD4. Tailoring ART monitoring strategies to specific settings with different available resources can improve clinical outcomes while remaining economically efficient.

The evolving role of CD4 cell counts in HIV care.

PURPOSE OF REVIEW: The role of the CD4 cell count in the management of people living with HIV is once again changing, most notably with a shift away from using CD4 assays to decide when to start antiretroviral therapy (ART). This article reflects on the past, current and future role of CD4 cell count testing in HIV programmes, and the implications for clinicians, programme managers and diagnostics manufacturers. RECENT FINDINGS: Following the results of recent randomized trials demonstrating the clinical and public health benefits of starting ART as soon as possible after HIV diagnosis is confirmed, CD4 cell count is no longer recommended as a way to decide when to initiate ART. For patients stable on ART, CD4 cell counts are no longer needed to monitor the response to treatment where HIV viral load testing is available. Nevertheless CD4 remains the best measurement of a patient's immune and clinical status, the risk of opportunistic infections, and supports diagnostic decision-making, particularly for patients with advanced HIV disease. SUMMARY: As countries revise guidelines to provide ART to all people living with HIV and continue to scale up access to viral load, strategic choices will need to be made regarding future investments in CD4 cell count and the appropriate use for clinical disease management.

Changes in weight and weight distribution across the lifespan among HIV-infected and -uninfected men and women.

Examine body composition changes across the lifespan of HIV-infected compared to uninfected adults. Longitudinal study of antiretroviral therapy (ART)-treated HIV-infected and uninfected participants from the Multicenter AIDS Cohort Study and Women's Interagency HIV Study. Body mass index (BMI), waist (WC), hip circumference (HC), and waist-to-height ratio (WHtR) measured at semiannual visits from 1999 to 2014. The age effect on outcomes over time was investigated using multivariate, piecewise, linear mixed-effect regression models adjusted for demographics, substance use, and comorbidities. Person-visits from 2363 men (1059 HIV-infected/1304 HIV-uninfected) and 2200 women (1455 HIV-infected/745 HIV-uninfected), median ages 45 [IQR 39,51] and 40 [32,46], respectively, were included. BMI gains were slower among HIV-infected participants of 40 years or less (P < 0.001), similar between HIV-infected and uninfected persons 40 to 60 years of age, and plateaued after age 60 in both groups. WC and WHtR increased across the age spectrum (P < 0.001) regardless of HIV serostatus, with significantly greater gains in HIV-infected men more than 60. Black race and Hispanic ethnicity were associated with greater BMI and WC. Lower BMI, WC, hip circumference, and WHtR were associated with hepatitis C infection among women only, and with substance use among all participants, and with lower CD4 cell count and shorter ART duration among HIV-infected participants. Slower BMI gain among younger HIV-infected adults may be partly explained by substance use and hepatitis C infection, and suggests that lower BMI does not represent improved health. Further analysis of muscle and fat abundance and quality will advance understanding of metabolic risk over the lifespan, a key to reducing morbidity in an aging population.

POC CD4 Testing Improves Linkage to HIV Care and Timeliness of ART Initiation in a Public Health Approach: A Systematic Review and Meta-Analysis.

BACKGROUND: CD4 cell count is an important test in HIV programs for baseline risk assessment, monitoring of ART where viral load is not available, and, in many settings, antiretroviral therapy (ART) initiation decisions. However, access to CD4 testing is limited, in part due to the centralized conventional laboratory network. Point of care (POC) CD4 testing has the potential to address some of the challenges of centralized CD4 testing and delays in delivery of timely testing and ART initiation. We conducted a systematic review and meta-analysis to identify the extent to which POC improves linkages to HIV care and timeliness of ART initiation. METHODS: We searched two databases and four conference sites between January 2005 and April 2015 for studies reporting test turnaround times, proportion of results returned, and retention associated with the use of point-of-care CD4. Random effects models were used to estimate pooled risk ratios, pooled proportions, and 95% confidence intervals. RESULTS: We identified 30 eligible studies, most of which were completed in Africa. Test turnaround times were reduced with the use of POC CD4. The time from HIV diagnosis to CD4 test was reduced from 10.5 days with conventional laboratory-based testing to 0.1 days with POC CD4 testing. Retention along several steps of the treatment initiation cascade was significantly higher with POC CD4 testing, notably from HIV testing to CD4 testing, receipt of results, and pre-CD4 test retention (all p<0.001). Furthermore, retention between CD4 testing and ART initiation increased with POC CD4 testing compared to conventional laboratory-based testing (p = 0.01). We also carried out a non-systematic review of the literature observing that POC CD4 increased the projected life expectancy, was cost-effective, and acceptable. CONCLUSIONS: POC CD4 technologies reduce the time and increase patient retention along the testing and treatment cascade compared to conventional laboratory-based testing. POC CD4 is, therefore, a useful tool to perform CD4 testing and expedite result delivery.

Lamivudine Monotherapy: Experience of Medium-term Outcomes in HIV-infected Children Unable to Adhere to Triple Therapy.

BACKGROUND: HIV-infected children in resource-poor settings who fail or default from first-line antiretroviral therapy have limited alternative options. By preferentially selecting the M184V mutation, lamivudine monotherapy (LM) is occasionally used while awaiting patient readiness for second- or third-line therapy, but this strategy has not been widely studied. METHODS: A retrospective review of all eligible LM events (≥3 months) from a cohort of two linked health facilities in the Eastern Cape Province, South Africa was undertaken. Events were disaggregated according to absolute CD4 count at initiation (Group 1: >200cells/µl, n=64; Group 2: ≤200cells/µl, n=7). Study endpoints were defined as a decline of absolute CD4 by ≥25% or to ≤200 cells/µl or World Health Organization stage 3 or 4 event (immunologic outcomes) or (re)initiation of second- or third-line therapy (real-world outcomes). RESULTS: Eligible LM events were identified among 71 children (56.4% male; median age at LM initiation 9.6 years). 71.8% (n = 51) had a drop in CD4 count of ≥25%, 15.6% (n = 10) of those whose CD4 counts had been >200 cells/µl dropped to ≤200 cells/µl and 8.1% (n = 6) experienced a stage 3 or 4 event; CD4 decreases and stage 3 or 4 events did not differ significantly between groups. No deaths were recorded. Children commencing LM with CD4 counts ≤200cells/µl had a shorter mean "real-world" duration of LM before switching to second/third line therapy (11.38 months vs. 26.1 months, P < 0.0001) and experienced immunologic outcomes at an earlier stage (5.29 vs. 9.2 months, P = 0.023). CONCLUSIONS: LM offers a potential alternative approach to antiretroviral therapy management in young patients pending availability and/or willingness to adhere to second- or third-line therapies but is associated with substantial immunologic decline. This strategy should be avoided in patients with CD4 ≤200 cells/µl.

Frailty and Constellations of Factors in Aging HIV-infected and Uninfected Women--The Women's Interagency HIV Study.

BACKGROUND: Biological similarities are noted between aging and HIV infection. Middle-aged adults with HIV infection may present as elderly due to accelerated aging or having more severe aging phenotypes occurring at younger ages. OBJECTIVES: We explored age-adjusted prevalence of frailty, a geriatric condition, among HIV+ and at risk HIV- women. DESIGN: Cross-sectional. SETTING: The Women's Interagency HIV Study (WIHS). PARTICIPANTS: 2028 middle-aged (average age 39 years) female participants (1449 HIV+; 579 HIV-). MEASUREMENTS: The Fried Frailty Index (FFI), HIV status variables, and constellations of variables representing Demographic/health behaviors and Aging-related chronic diseases. Associations between the FFI and other variables were estimated, followed by stepwise regression models. RESULTS: Overall frailty prevalence was 15.2% (HIV+, 17%; HIV-, 10%). A multivariable model suggested that HIV infection with CD4 count<200; age>40 years; current or former smoking; income ≤$12,000; moderate vs low fibrinogen-4 (FIB-4) levels; and moderate vs high estimated glomerular filtration rate (eGFR) were positively associated with frailty. Low or moderate drinking was protective. CONCLUSIONS: Frailty is a multidimensional aging phenotype observed in mid-life among women with HIV infection. Prevalence of frailty in this sample of HIV-infected women exceeds that for usual elderly populations. This highlights the need for geriatricians and gerontologists to interact with younger 'at risk' populations, and assists in the formulation of best recommendations for frailty interventions to prevent early aging, excess morbidities and early death.

The Impact of Comprehensive Case Management on HIV Client Outcomes.

In 1990, New York State instituted Comprehensive Medicaid Case Management, also known as Target Case Management (TCM), for people dealing with multiple comorbid conditions, including HIV. The goal of TCM is to assist clients in navigating the health care system to increase care engagement and treatment adherence for individuals with complex needs. HIV-positive individuals engaged in care are more likely to be virally suppressed, improving clinical outcomes and decreasing chances of HIV transmission. The purpose of this study was to understand the impact of TCM management on outcomes for people with HIV. Data were obtained from Amida Care, which operates not-for-profit managed care Medicaid and Medicare Special Needs Plans (SNPs) for HIV clients. Changes in clinical, cost, as well as medical and pharmacy utilization data among TCM clients were examined between January 2011 through September 2012 from the start of case management enrollment through the end of the study period (i.e., up to 6 months after disenrollment). Additionally, CD4 counts were compared between Amida Care TCM clients and non-TCM clients. Notable findings include increased CD4 counts for TCM clients over the one-year study period, achieving parity with non-TCM clients (i.e., Mean CD4 count > 500). When looking exclusively at TCM clients, there were increases in medication costs over time, which were concomitant with increased care engagement. Current findings demonstrate that TCM is able to achieve its goals of improving care engagement and treatment adherence. Subsequent policy changes resulting from the Affordable Care Act and the New York State Medicaid Redesign have made the Health Home the administrator of TCM services. Government entities charged with securing and managing TCM and care coordination for people with HIV should provide thoughtful and reasonable guidance and oversight in order to maintain optimal clinical outcomes for TCM clients and reduce the transmission of HIV.

Point-of-care CD4 testing to inform selection of antiretroviral medications in south african antenatal clinics: a cost-effectiveness analysis.

BACKGROUND: Many prevention of mother-to-child HIV transmission (PMTCT) programs currently prioritize antiretroviral therapy (ART) for women with advanced HIV. Point-of-care (POC) CD4 assays may expedite the selection of three-drug ART instead of zidovudine, but are costlier than traditional laboratory assays. METHODS: We used validated models of HIV infection to simulate pregnant, HIV-infected women (mean age 26 years, gestational age 26 weeks) in a general antenatal clinic in South Africa, and their infants. We examined two strategies for CD4 testing after HIV diagnosis: laboratory (test rate: 96%, result-return rate: 87%, cost: $14) and POC (test rate: 99%, result-return rate: 95%, cost: $26). We modeled South African PMTCT guidelines during the study period (WHO "Option A"): antenatal zidovudine (CD4 ≤350/µL) or ART (CD4>350/µL). Outcomes included MTCT risk at weaning (age 6 months), maternal and pediatric life expectancy (LE), maternal and pediatric lifetime healthcare costs (2013 USD), and cost-effectiveness ($/life-year saved). RESULTS: In the base case, laboratory led to projected MTCT risks of 5.7%, undiscounted pediatric LE of 53.2 years, and undiscounted PMTCT plus pediatric lifetime costs of $1,070/infant. POC led to lower modeled MTCT risk (5.3%), greater pediatric LE (53.4 years) and lower PMTCT plus pediatric lifetime costs ($1,040/infant). Maternal outcomes following laboratory were similar to POC (LE: 21.2 years; lifetime costs: $23,860/person). Compared to laboratory, POC improved clinical outcomes and reduced healthcare costs. CONCLUSIONS: In antenatal clinics implementing Option A, the higher initial cost of a one-time POC CD4 assay will be offset by cost-savings from prevention of pediatric HIV infection.

Using a call center to encourage linkage to care following mobile HIV counseling and testing.

Engaging newly diagnosed HIV+ individuals in treatment is a significant global challenge. As South Africa expands HIV counseling and testing (HCT) services, the growing numbers of people diagnosed with HIV will need innovative links to care approaches in order for treatment to be most effective. While definitions vary, we have defined "linkage to care" as connecting an HIV+ individual to medical care, so that CD4 cell test results are obtained and antiretroviral therapy (ART) eligibility assessed. The study is of HIV+ participants (n = 1096), from either Limpopo or Gauteng provinces from a "Links to Care" program. A two-pronged expanded HCT service was used, which included a community outreach approach to address HIV testing and a call center to encourage and track each patient's linkage to care post-HIV diagnosis. The majority of individuals (51%) were linked to care with a mean time to linkage of 31 days (with most individuals linked in less than 14 days). More females (54%) were linked to care than males (47%) and had higher CD4 cell counts than males; females had a mean CD4 cell count of 440, while males took longer to link to care and had a lower mean CD4 cell count of 331. Females of 23 years or younger had the lowest linkage rate of all females. Findings suggest that expanding HCT services to include innovative links to care approaches can improve linkage to care and subsequently impact HIV prevention.