[Show abstract][Hide abstract] ABSTRACT: Equitable access to antiretroviral therapy (ART) for men and women with human immunodeficiency virus (HIV) infection is a principle endorsed by most countries and funding bodies, including the U.S. President's Emergency Plan for AIDS (acquired immunodeficiency syndrome) Relief (PEPFAR) (1). To evaluate gender equity in ART access among adults (defined for this report as persons aged ≥15 years), 765,087 adult ART patient medical records from 12 countries in five geographic regions* were analyzed to estimate the ratio of women to men among new ART enrollees for each calendar year during 2002-2013. This annual ratio was compared with estimates from the Joint United Nations Programme on HIV/AIDS (UNAIDS)(†) of the ratio of HIV-infected adult women to men in the general population. In all 10 African countries and Haiti, the most recent estimates of the ratio of adult women to men among new ART enrollees significantly exceeded the UNAIDS estimates for the female-to-male ratio among HIV-infected adults by 23%-83%. In six African countries and Haiti, the ratio of women to men among new adult ART enrollees increased more sharply over time than the estimated UNAIDS female-to-male ratio among adults with HIV in the general population. Increased ART coverage among men is needed to decrease their morbidity and mortality and to reduce HIV incidence among their sexual partners. Reaching more men with HIV testing and linkage-to-care services and adoption of test-and-treat ART eligibility guidelines (i.e., regular testing of adults, and offering treatment to all infected persons with ART, regardless of CD4 cell test results) could reduce gender inequity in ART coverage.
Full-text · Article · Nov 2015 · MMWR. Morbidity and mortality weekly report
[Show abstract][Hide abstract] ABSTRACT: During 2004-2009, >12,000 children (<15 years old) initiated antiretroviral therapy (ART) in Mozambique. Nationally representative outcomes and temporal trends in outcomes were investigated.
Rates of death, loss to follow-up (LTFU), and attrition (death or LTFU) were evaluated in a nationally representative sample of 1,054 children, who initiated ART during 2004-2009 at 25 facilities randomly selected using probability-proportional-to-size sampling.
At ART initiation during 2004-2009, 50% were male, median age was 3.3 years, median CD4% was 13%, median CD4 count was 375 cells/µL, and median weight-for-age z-score was -2.1. During 2004-2009, median time from HIV diagnosis to care initiation declined from 33 to 0 days (p=0.001), median time from care to ART declined from 93 to 62 days (p=0.004), the percentage aged <2 at ART initiation increased from 16% to 48% (p=0.021), the percentage of patients with prior tuberculosis declined from 50% to 10% (p=0.009), and the percentage with prior lymphocytic interstitial pneumonia declined from 16% to 1% (p<0.001). Over 2,652 person-years of ART, 183 children became LTFU and 26 died. Twelve-month attrition was 11% overall, but increased from 3% to 22% during 2004-2009, due mainly to increases in 12-month LTFU (from 3% to 18%).
Declines in the prevalence of markers of advanced HIV disease at ART initiation probably reflect increasing ART access. However, 12-month LTFU increased during program expansion, and this negated any program improvements in outcomes that might have resulted from earlier ART initiation.
[Show abstract][Hide abstract] ABSTRACT: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration.
Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained.
A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.
[Show abstract][Hide abstract] ABSTRACT: Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about 30% in the global annual number of human immunodeficiency (HIV)-related deaths and declines in global HIV incidence, estimated annual HIV-related deaths among adolescents have increased by about 50% and estimated adolescent HIV incidence has been relatively stable. In 2012, an estimated 2,500 (40%) of all 6,300 daily new HIV infections occurred among persons aged 15-24 years. Difficulty enrolling adolescents and young adults in ART and high rates of loss to follow-up (LTFU) after ART initiation might be contributing to mortality and HIV incidence in this age group, but data are limited. To evaluate age-related ART retention challenges, data from retrospective cohort studies conducted in seven African countries among 16,421 patients, aged ≥15 years at enrollment, who initiated ART during 2004-2012 were analyzed. ART enrollment and outcome data were compared among three groups defined by age at enrollment: adolescents and young adults (aged 15-24 years), middle-aged adults (aged 25-49 years), and older adults (aged ≥50 years). Enrollees aged 15-24 years were predominantly female (81%-92%), commonly pregnant (3%-32% of females), unmarried (54%-73%), and, in four countries with employment data, unemployed (53%-86%). In comparison, older adults were more likely to be male (p<0.001), employed (p<0.001), and married, (p<0.05 in five countries). Compared with older adults, adolescents and young adults had higher LTFU rates in all seven countries, reaching statistical significance in three countries in crude and multivariable analyses. Evidence-based interventions to reduce LTFU for adolescent and young adult ART enrollees could help reduce mortality and HIV incidence in this age group.
Full-text · Article · Nov 2014 · MMWR. Morbidity and mortality weekly report
[Show abstract][Hide abstract] ABSTRACT: Estimation of HIV-1 incidence is an important public health tool for understanding the status of the epidemic, identifying high-risk populations, and assessing various intervention strategies. Several laboratory-based methods have been developed for distinguishing recent from long-term HIV-1 infection; however, each exhibits some degree of misclassification, particularly among AIDS patients and those taking antiretroviral therapy (ART). To improve upon the limitations associated with measuring responses to a single analyte, we have developed a bead-based, multiplex assay for determination of HIV recent infection based on total antibody binding and antibody avidity to multiple analytes. An HIV-specific, multiplex panel was created by coupling the recombinant HIV-1 proteins p66, gp120, gp160, and gp41 to Bio-Plex COOH microspheres. Longitudinal plasma specimens from recent seroconverters were tested for reactivity to the coupled microspheres using the Bio-Plex 200 System. For each analyte, HIV-specific antibody binding and avidity increased for 1-2 years post-seroconversion, leading to a significant difference in reactivity between recent and long-term specimens. While the potential for misclassification of individuals diagnosed with AIDS or receiving ART appears to be minimal with avidity measures, the impact on total antibody binding was variable, depending on the individual analyte. This bead-based, HIV-specific multiplex assay measures several distinct immune responses in a single assay plate, allowing for sampling of multiple analytes in the determination of recent infection, which could aid in the development of improved statistical methods or algorithms that will more accurately estimate HIV incidence.
No preview · Article · Jun 2011 · AIDS research and human retroviruses
[Show abstract][Hide abstract] ABSTRACT: Quality assurance (QA) is a systematic process to monitor and improve clinical laboratory practices. The fundamental components of a laboratory QA program include providing a functional and safe laboratory environment, trained and competent personnel, maintained equipment, adequate supplies and reagents, testing of appropriate specimens, internal monitoring of quality, accurate reporting, and external quality assessments. These components are necessary to provide accurate and precise CD4 T-cell counts, an essential test to evaluate start of and monitor effectiveness of antiretroviral therapy for HIV-infected patients. In recent years, CD4 testing has expanded dramatically in resource-limited settings. Information on a CD4 QA program as described in this article will provide guidelines not only for clinical laboratory staff but also for managers of programs responsible for supporting CD4 testing. All agencies involved in implementing CD4 testing must understand the needs of the laboratory and provide advocacy, guidance, and financial support to established CD4 testing sites and programs. This article describes and explains the procedures that must be put in place to provide reliable CD4 determinations in a variety of settings.
No preview · Article · Oct 2010 · American Journal of Clinical Pathology
[Show abstract][Hide abstract] ABSTRACT: The expansion of HIV/AIDS care and treatment in resource-constrained countries, especially in sub-Saharan Africa, has generally developed in a top-down manner. Further expansion will involve primary health centers where human and other resources are limited. This article describes the World Health Organization/President's Emergency Plan for AIDS Relief collaboration formed to help scale up HIV services in primary health centers in high-prevalence, resource-constrained settings. It reviews the contents of the Operations Manual developed, with emphasis on the Laboratory Services chapter, which discusses essential laboratory services, both at the center and the district hospital level, laboratory safety, laboratory testing, specimen transport, how to set up a laboratory, human resources, equipment maintenance, training materials, and references. The chapter provides specific information on essential tests and generic job aids for them. It also includes annexes containing a list of laboratory supplies for the health center and sample forms.
Full-text · Article · Jul 2009 · American Journal of Clinical Pathology
[Show abstract][Hide abstract] ABSTRACT: Serodiagnosis of human immunodeficiency virus (HIV) infection in the United States has traditionally relied on a sequential two-test algorithm: an initial screen with an enzyme immunoassay (EIA) and reflex testing of EIA-reactive specimens with a more specific supplemental test such as Western blotting or immunofluorescence. The supplemental tests are tedious, subjective, and expensive. In addition, there have been major improvements in the performance and accuracy of the EIA tests as well as the introduction of rapid serologic tests (RT) and HIV nucleic acid amplification tests (NAAT). Related to these improvements is the possibility that alternative algorithms using combinations of currently approved HIV tests may function as well as if not better than the current algorithm, with more flexibility, improved accuracy, and lower cost. To this end, we evaluated the performance of 12 currently licensed tests and 1 in-house HIV test (6 EIA, 4 RT, and 3 NAAT) on panels of plasma samples from HIV-infected (n = 621 HIV type 1 [HIV-1] and 34 HIV-2) and uninfected (n = 513) people and of sequential specimens from people early in seroconversion (183 specimens from 15 patients). Test combinations were analyzed in two dual-test (sensitivity-optimized and specificity-optimized) algorithms and in a three-test (tie-breaking) algorithm, and performance was compared to the conventional algorithm. The results indicate that alternative algorithm strategies with currently licensed tests compare favorably with the conventional algorithm in detecting and confirming established HIV infection. Furthermore, there was a lower frequency of discordant or indeterminate results that require follow-up testing, and there was improved detection of early infection.
Full-text · Article · Jun 2008 · Journal of clinical microbiology
[Show abstract][Hide abstract] ABSTRACT: The global HIV/AIDS pandemic and guidelines for initiating anti-retroviral therapy (ART) and opportunistic infection prophylaxis demand affordable, reliable, and accurate CD4 testing. A simple innovative approach applicable to existing technology that has been successfully applied in resource-challenged settings, PanLeukogated CD4 (PLG), could offer solutions for cost saving and improved precision.
Day-old whole blood from 99 HIV+ donors was simultaneously studied in five North-American laboratories to compare the performance of their predicate methods with the dual-platform PLG method. The predicate technology included varying 4-color CD45/CD3/CD4/CD8 protocols on different flow cytometers. Each laboratory also assayed eight replicate specimens of day-old blood from 10 to 14 local donors. Bias and precision of predicate and PLG methods was studied between- and within-participating laboratories.
Significantly (P < 0.0001) improved between-laboratory precision/coefficient of variation (CV%) was noted using the PLG method (overall median 9.3% vs. predicate median CV 13.1%). Within-laboratory precision was also significantly (P < 0.0001) better overall using PLG (median 4.6% vs. predicate median CV 6.2%) and in 3 of the 5 laboratories. PLG counts tended to be 11% smaller than predicate methods (P < 0.0001) for shipped (median of predicate-PLG = 31) and local specimens (median of predicate-PLG = 23), both overall and in 4 of 5 laboratories (median decreases of 4, 16, 20, and 21% in shipped specimens); the other laboratory had a median increase of 5%.
Laboratories using predicate CD4 methods similar to those in this study could improve their between-laboratory and their within-laboratory precision, and reduce costs, by switching to the PLG method after adequate training, if a change (usually, a decrease) in CD4 counts is acceptable to their health systems.
Full-text · Article · Jan 2008 · Cytometry Part B Clinical Cytometry
[Show abstract][Hide abstract] ABSTRACT: Persons occupationally exposed to nonhuman primates (NHPs) can be persistently infected with simian foamy virus (SFV). The clinical significance and person-to-person transmissibility of zoonotic SFV infection is unclear. Seven SFV-infected men responded to annual structured interviews and provided whole blood, oral, and urogenital specimens for study. Wives were tested for SFV infection. Proviral DNA was consistently detected by PCR in PBMCs of infected men and inconsistently in oral or urogenital samples. SFV was infrequently cultured from their PBMCs and throat swabs. Despite this and a long period of intimate exposure (median 20 years), wives were SFV negative. Most participants reported nonspecific symptoms and diseases common to aging. However, one of two persons with mild thrombocytopenia had clinically asymptomatic nonprogressive, monoclonal natural killer cell lymphocytosis of unclear relationship to SFV. All participants worked with NHPs before 1988 using mucocutaneous protection inconsistently; 57% described percutaneous injuries involving the infecting NHP species. SFV likely transmits to humans through both percutaneous and mucocutaneous exposures to NHP body fluids. Limited follow-up has not identified SFV-associated illness and secondary transmission among humans.
No preview · Article · Dec 2007 · AIDS Research and Human Retroviruses
[Show abstract][Hide abstract] ABSTRACT: We present the largest longitudinal study to date that examines the association between Kaposi's Sarcoma (KS) disease progression and the presence and viral load of human herpesvirus 8 (HHV-8).
Ninety-six men were enrolled at HIV clinics in Atlanta, Georgia, who had KS (n = 47) or were without KS but seropositive for HHV-8. Visits occurred at 6-month intervals for 2 years at which the patient's KS status was evaluated and oral fluid and blood were collected for quantification of HHV-8 DNA and antibodies.
The presence of HHV-8 DNA in blood was more common (P < 0.001) and the viral load higher (P < 0.001) in men with KS in comparison with men without KS. Mean HHV-8 viral loads in blood and oral fluids were associated with disease status, being highest among patients with progressing KS, intermediate among patients with stable KS, and lowest among patients with regressing KS. Consistent with our previous report high antibody titers to HHV-8 orf 65 were inversely associated with HHV-8 shedding in oral fluid.
We observed a significant association between changes in KS disease severity and the presence and viral load of HHV-8. HHV-8 viral load in blood may provide useful information to clinicians for assessment of the risk of further disease progression in patients with KS.
[Show abstract][Hide abstract] ABSTRACT: The success of antiretroviral therapy is known to be compromised by drug-resistant HIV-1 at frequencies detectable by conventional bulk sequencing. Currently, there is a need to assess the clinical consequences of low-frequency drug resistant variants occurring below the detection limit of conventional genotyping. Sensitive detection of drug-resistant subpopulations, however, requires simple and practical methods for routine testing.
We developed highly-sensitive and simple real-time PCR assays for nine key drug resistance mutations and show that these tests overcome substantial sequence heterogeneity in HIV-1 clinical specimens. We specifically used early wildtype virus samples from the pre-antiretroviral drug era to measure background reactivity and were able to define highly-specific screening cut-offs that are up to 67-fold more sensitive than conventional genotyping. We also demonstrate that sequencing the mutation-specific PCR products provided a direct and novel strategy to further detect and link associated resistance mutations, allowing easy identification of multi-drug-resistant variants. Resistance mutation associations revealed in mutation-specific amplicon sequences were verified by clonal sequencing.
Combined, sensitive real-time PCR testing and mutation-specific amplicon sequencing provides a powerful and simple approach that allows for improved detection and evaluation of HIV-1 drug resistance mutations.
[Show abstract][Hide abstract] ABSTRACT: To examine trends in HIV prevalence in the US household population, serum or urine samples from 2 National Health and Nutrition Examinations Surveys (NHANES) (1988-1994 and 1999-2002), were tested for HIV antibody. In the 1999 to 2002 survey, data on risk behaviors, CD4 T lymphocytes, and antiretroviral therapy (ART) were also available. In the 1988 to 1994 survey, there were 59 positive individuals of 11,203 tested. In NHANES 1999 to 2002, there were 32 positive individuals of 5926 tested. The prevalence of HIV infection among those aged 18 to 39 years in NHANES 1988 to 1994 was 0.38% (95% confidence interval [CI]: 0.22-0.68) as compared with 0.37% (95% CI: 0.17 to 0.80) in 1999 to 2002. Prevalence did not change significantly between surveys in any race and/or ethnic or gender group among 18- to 39-year-old participants. HIV prevalence was 3.58% (95% CI: 1.88 to 6.71) among non-Hispanic blacks in the 40- to 49-year-old age group in 1999 to 2002, but the age range available in NHANES 1988 to 1994 was 18 to 59 years and does not allow direct comparison of prevalence. Cocaine use and the presence of herpes simplex virus-2 antibody were the only significant risk factors for HIV infection for non-Hispanic blacks. Fifty-eight percent of infected individuals not reporting ART had CD4 T-lymphocyte counts < 200 cells/mm3 compared with 18.2% on therapy and 12.5% of participants newly informed of their HIV status.
No preview · Article · May 2006 · JAIDS Journal of Acquired Immune Deficiency Syndromes
[Show abstract][Hide abstract] ABSTRACT: Use of the standard dual-platform flow cytometric method for determination of CD4+ T-lymphocyte counts, which needs both a flow cytometer (FCM) and hematological analyzer, would inevitably lead to increased
variability. The development of new single-platform (SP) FCMs that provide direct CD4+ T-lymphocyte counts for improved assay precision and accuracy have recently attracted attention. This study evaluated one
of those systems, CyFlowgreen (Partec), a single-parameter SP volumetric FCM. The performance of CyFlowgreen was compared with those of two reference standard SP microbead-based technologies of the three-color TruCOUNT tube with the
FACScan FCM and a two-color FACSCount system (Becton Dickinson Biosciences). Absolute CD4+ and CD8+ T-lymphocyte counts in 200 human immunodeficiency virus type 1-seropositive blood specimens were determined. Statistical
analysis for correlation and agreement were performed. A high correlation of absolute CD4 counts was shown when those obtained
with CyFlowgreen were compared with those obtained with the bead-based three-color TruCOUNT system (R2 = 0.96; mean bias, −69.1 cells/μl; 95% confidence interval [CI], −225.7 to +87.5 cells/μl) and the FACSCount system (R2 = 0.97; mean bias, −40.0 cells/μl; 95% CI, −165.1 to +85.1 cells/μl). The correlation of the CD4+ T-lymphocyte counts obtained by the two bead-based systems was high (R2 = 0.98). Interestingly, CyFlowgreen yielded CD4+ T-lymphocyte counts that were 21.8 and 7.2 cells/μl lower than those obtained with the TruCOUNT and the FACSCount systems,
respectively, when CD4+ T-lymphocyte counts were <250 CD4+ T-lymphocyte counts/μl range or 17.3 and 5.8 cells/μl less, respectively, when CD4+ T-lymphocyte counts were <200 cells/μl. The single-parameter CyFlowgreen volumetric technology performed well in comparison with the performance of the standard SP bead-based FCM system. However,
a multicenter comparative study is needed before this FCM machine is implemented in resource-limited settings.
Preview · Article · Jan 2006 · Clinical and Diagnostic Laboratory Immunology