Reactive HIV Research Articles

The Prevalence and Correlates of Receiving Confirmatory HIV Test Results Among Newly Diagnosed HIV-Positive Individuals at a Community-Based Testing Center

This study examined the prevalence and correlates of completing the HIV testing process-specifically receiving a confirmatory HIV test and returning for the results-in a sample of newly diagnosed HIV-positive individuals at an HIV testing center in New York City. Of the 213 individuals who received a reactive rapid HIV test result, 82% received a confirmatory HIV test. Of the 236 individuals who received a positive result on a rapid or traditional HIV test that was validated by a positive confirmatory HIV test, 65% returned for the confirmatory test results. Multivariate analyses revealed that being a non-U.S. citizen, homeless/living in transitional housing, being uninsured, and testing off-site were significantly associated with completing the HIV testing process. The findings indicate the need to explore strategies that address obstacles to receiving confirmatory HIV testing and returning for the results, in addition to the feasibility of a rapid confirmatory HIV test.

Comprehensive analysis of unique cases with extraordinary control over HIV replication

AbstractTrue long-term nonprogressors (LTNPs)/elite controllers (ECs) maintain durable control over HIV replication without antiretroviral therapy. Herein we describe 4 unique persons who were distinct from conventional LTNPs/ECs in that they had extraordinarily low HIV burdens and comparatively weak immune responses. As a group, typical LTNPs/ECs have unequivocally reactive HIV-1 Western blots, viral loads below the lower threshold of clinical assays, low levels of persistent viral reservoirs, an over-representation of protective HLA alleles, and robust HIV-specific CD8+ T-cell responses. The 4 unique cases were distinguished from typical LTNPs/ECs based on weakly reactive Western blots, undetectable plasma viremia by a single copy assay, extremely low to undetectable HIV DNA levels, and difficult to isolate replication-competent virus. All 4 had at least one protective HLA allele and CD8+ T-cell responses that were disproportionately high for the low antigen levels but comparatively lower than those of typical LTNPs/ECs. These unique persons exhibit extraordinary suppression over HIV replication, therefore, higher-level control than has been demonstrated in previous studies of LTNPs/ECs. Additional insight into the full spectrum of immune-mediated suppression over HIV replication may enhance our understanding of the associated mechanisms, which should inform the design of efficacious HIV vaccines and immunotherapies.

Enhanced U.S. Army HIV Diagnostic Algorithm Used to Diagnose Acute HIV Infection in a Deployed Soldier

Antibody screening alone may fail to detect human immunodeficiency virus (HIV) in recently infected individuals. By U.S. Army regulation, HIV-infected soldiers are not permitted to deploy to areas of conflict, including Iraq and Afghanistan. We report here the first case of acute HIV infection (AHI) in a soldier in a combat area of operation detected by an enhanced U.S. Army HIV testing algorithm and discuss features of the tests which aided in clinical diagnosis. We tested the sample from the AHI case with a third generation HIV-1/HIV-2 plus O enzyme immunoassay, HIV-1 Western Blot, and a qualitative HIV-1 ribonucleic acid molecular diagnostic assay. Risk factors for HIV acquisition were elicited in an epidemiologic interview. Evaluation of the blood sample for AHI indicated an inconclusive serologic profile and a reactive HIV-1 ribonucleic acid result. The main risk factor for acquisition reported was unprotected sexual intercourse with casual strangers in the U.S. while on leave during deployment. The clinical diagnosis of AHI in a combat area of operation is important. Diagnosis of HIV is key to preventing adverse effects to the infected soldier from deployment stressors of deployment and further transmission via parenteral or sexual exposures.

HIV-2 antibody detection after indeterminate or negative HIV-1 Western blot in Cuba, 2005-2008

INTRODUCTION Differentiating between HIV-1 and HIV-2 infection is the first step to understanding HIV transmission, epidemiology and pathogenesis in geographical areas where both viruses circulate. In Cuba, positive results in mixed HIV-1/2 screening assays are confirmed by HIV-1 Western blot. Indeterminate results constitute the main limitation of this test and HIV-2 infection is among their possible causes; hence the importance of second-stage screening and confirmatory tests for HIV-2 infection. OBJECTIVE Investigate the contribution of HIV-2 antibodies to negative or indeterminate HIV-1 Western blot results in serum samples from 2005 through 2008 in Cuba. METHODS HIV-2 reactivity was studied using the ELISA DAVIH-VIH-2 diagnostic kit (Cuba) in 1723 serum samples with negative or indeterminate results for HIV-1 Western blot from January 2005 through December 2008. Duplicate sera reactive by ELISA were confirmed by HIV-2 Western blot, results interpreted according to WHO criteria. The epidemiological interview established by Cuba's National Program for Prevention and Control Sexually-Transmitted Diseases and HIV/AIDS was applied to HIV-2 Western blot-positive patients. RESULTS Among all sera studied, HIV-2 ELISA identified 12 reactive serum samples (0.70%) and 1711 non-reactive (99.30%). Western blot analysis of the 12 ELISA-reactive samples confirmed two positive samples (16.67%), 4 negative (33.33%) and 6 indeterminate (50%). Positive samples reacted against the p16, p26, gp36, p53, p56, p68 and gp105 proteins. All 12 ELISA-reactive samples belonged to the HIV-1 Western blot indeterminate group. The two HIV-2-positive samples showed well defined reactivity to gp160, p53, p55 and p34 of HIV-1. HIV-1 seroconversion was observed in all 10 remaining samples during serological followup. CONCLUSIONS Two new HIV-2 seropositive cases were diagnosed using DAVIH-VIH-2 and HIV-2 Western blot in indeterminate HIV-1 Western blot samples. Results support the recommendation that HIV-2 Western blot be included in the diagnostic algorithm for HIV-1/2 to followup negative or indeterminate HIV-1 Western blot results.

Successful treatment of bilateral visual loss caused by HIV-associated optic neuritis

Optic neuritis is not an uncommon diagnosis in HIV-infected patients, but it is rarely idiopathic. We report a case of a young HIV-infected woman who developed optic neuritis as her presenting manifestation of HIV infection. She had initially experienced sudden-onset right-sided painful visual loss; the left eye had become involved within days. Bilateral swollen discs were apparent on fundoscopy. Investigations were performed for meningitis (including bacterial, cryptococcal, tuberculous and syphilitic types), auto-immune diseases, toxoplasma, rubella, cytomegalovirus, viral hepatitis, HTLV-1/2, HIV-1/2 and syphilis. The only positive result was a reactive HIV enzyme-linked immunosorbent assay. The CD4 count was 85 cells/µl. A post-contrast magnetic resonance imaging scan of the brain illustrated enhancement of the optic nerves. Treatment was 3 days of intravenous methylprednisolone 1 g daily, followed by 11 days of oral prednisone 60 mg daily. Highly active antiretroviral therapy was initiated after 2 weeks. Vision improved from day 6 after commencement of steroid therapy, with ongoing recovery at 5 months.

Comparison of alternative interpretive criteria for the HIV-1 Western blot and results of the Multispot HIV-1/HIV-2 Rapid Test for classifying HIV-1 and HIV-2 infections

Background HIV-1 Western blot (WB) may be positive in specimens from persons with HIV-2 infection due to cross-reactive antibodies. HIV-1 and HIV-2 infections may be identified using assays designed to differentiate HIV-1 and HIV-2 antibody reactivity. Objectives To evaluate the ability of the current CDC WB criteria, alternative more stringent HIV-1 WB criteria (2 env plus one gag or pol band) and the Multispot HIV-1/HIV-2 Rapid Test to accurately differentiate HIV-1 and HIV-2 infections. Study design Two panels were used to determine the ability of each method to properly classify HIV-1 and HIV-2 infections: an HIV-2 panel ( n = 114) determined to be HIV-2 antibody-positive by both Multispot and by a validated HIV-2 WB, and 2135 HIV-1/HIV-2 immunoassay repeatedly reactive (IA-RR) specimens from the New York State Department of Health Laboratory (NYS). Results By CDC WB criteria, 53 (46.5%) HIV-2 panel specimens were HIV-1 WB positive, 60 (52.6%) were indeterminate, and 1 (0.9%) was negative; the alternative WB criteria re-classified 75.5% of the positives as indeterminate. Among 2135 NYS IA-RR specimens, the alternative WB criteria increased the proportion of indeterminates by 0.8%. Only 6 (0.3%) of the NYS specimens were determined to be HIV-2 infections; all 6 were classified either as HIV-1 positive or indeterminate by both WB criteria, but were classified as HIV-2 ( n = 4) or HIV-1/2 undifferentiated ( n = 2) by Multispot. Conclusions The alternative WB criteria classified most of the HIV-2 specimens that were HIV-1 positive by CDC criteria as indeterminate, but also slightly increased the proportion of HIV-1 specimens classified as indeterminate. The WB indeterminate specimens would require further testing or follow-up to resolve the infection status, whereas Multispot directly distinguished HIV-1 from HIV-2.

Use of a rapid HIV testing algorithm to improve linkage to care

Background Awaiting definitive diagnosis before scheduling healthcare visits complicates HIV screening and referral. Clients screened by rapid tests as initially reactive often fail to return to receive definitive test results, are not linked to care and enter care late or not at all. Objectives To evaluate statewide, (1) the accuracy of a single-visit, two test HIV rapid testing algorithm (RTA) and (2) its effect on referral to care for positive clients. Study design A two-test RTA was implemented at 24 sites in New Jersey beginning in December 2008. All clients with a reactive rapid HIV test were offered a second rapid HIV test, and RTA results were compared with Western blot (WB). Referral to care occurred based upon two sequential positive rapid tests. Results The RTA program has screened 51,413 individuals obtaining 426 reactive rapid test results; 394 (92.5%) were reactive by a second rapid test, 32 (7.5%) had a negative second rapid test. Twenty-eight individuals refused WB testing. Of 369 RTA-positive individuals who have WB results, 368 (99.5%) were confirmed positive. Of RTA-positive clients, 290 (73.6%), including 25 (6.6%) who refused Western blot, were immediately referred for care including one individual with a false-positive RTA. Conclusions The RTA reduced false positive results by 6.2% and agreed with WB results 99.5% of the time. Improved referral to care compared to traditional rapid HIV screening occurs when immediate referral is based on RTA verification of a preliminary positive rapid test. WB confirmation is not essential for effective screening and contributes to difficulties linking individuals to care.

Polyclonal B cell responses to conserved neutralization epitopes in a subset of HIV-1-infected individuals.

A small proportion of HIV-infected individuals generate a neutralizing antibody (NAb) response of exceptional magnitude and breadth. A detailed analysis of the critical epitopes targeted by broadly neutralizing antibodies should help to define optimal targets for vaccine design. HIV-1-infected subjects with potent cross-reactive serum neutralizing antibodies were identified by assaying sera from 308 subjects against a multiclade panel of 12 "tier 2" viruses (4 each of subtypes A, B, and C). Various neutralizing epitope specificities were determined for the top 9 neutralizers, including clade A-, clade B-, clade C-, and clade A/C-infected donors, by using a comprehensive set of assays. In some subjects, neutralization breadth was mediated by two or more antibody specificities. Although antibodies to the gp41 membrane-proximal external region (MPER) were identified in some subjects, the subjects with the greatest neutralization breadth targeted gp120 epitopes, including the CD4 binding site, a glycan-containing quaternary epitope formed by the V2 and V3 loops, or an outer domain epitope containing a glycan at residue N332. The broadly reactive HIV-1 neutralization observed in some subjects is mediated by antibodies targeting several conserved regions on the HIV-1 envelope glycoprotein.

An immunological comparison between lipidated and non-lipidated multivalent HIV-1 peptides representing Gp120 and Gag hypervariable regions

Despite the extensive efforts towards development of an effective HIV vaccine, major challenges surrounding vaccine design still exist. We have previously developed a unique multivalent HIV-1 candidate vaccine representing hypervariable Gp120 and Gag regions. This candidate vaccine was able to induce a broad cell-mediated immune response in HLA-A2.1 mice and non-human primates against HIV-1 subtypes A–F. Herein, the reactivity of each hypervariable peptide mixture within our candidate peptide vaccine was further characterized to optimize the final vaccine formulation for the future clinical studies. The binding of each hypervariable region to sera from HIV-infected individuals demonstrated a strong reactivity between the antibodies and hypervariable regions. In addition, 15 groups of mice were immunized with adjuvant alone or each individual peptide mixture (lipidated or non-lipidated) to evaluate the ability of each variable region to induce humoral and cellular immune responses against HIV-1. A reactive HIV-1 specific immune response was detected among the immunized groups; however, mice receiving the Gag hypervariable regions demonstrated the highest frequency of cell-mediated immune responses.

Towards targeted screening for acute HIV infections in British Columbia.

BackgroundOur objective was to describe the characteristics of acute and established HIV infections diagnosed in the Canadian province of British Columbia. Province-wide HIV testing and surveillance data were analyzed to inform recommendations for targeted use of screening algorithms to detect acute HIV infections.MethodsAcute HIV infection was defined as a confirmed reactive HIV p24 antigen test (or HIV nucleic acid test), a non-reactive or reactive HIV EIA screening test and a non-reactive or indeterminate Western Blot. Characteristics of unique individuals were identified from the British Columbia HIV/AIDS Surveillance System. Primary drug resistance and HIV subtypes were identified by analyzing HIV pol sequences from residual sera from newly infected individuals.ResultsFrom February 2006 to October 2008, 61 individuals met the acute HIV infection case definition, representing 6.2% of the 987 newly diagnosed HIV infections during the analysis period. Acute HIV infection cases were more likely to be men who have sex with men (crude OR 1.71; 95% CI 1.01-2.89], to have had a documented previous negative HIV test result (crude OR 2.89; 95% CI 1.52-5.51), and to have reported a reason for testing due to suspected seroconversion symptoms (crude OR 5.16; 95% CI 2.88-9.23). HIV subtypes and rates of transmitted drug resistance across all classes of drugs were similar in persons with both acute and established HIV infections.ConclusionsTargeted screening to detect acute HIV infection is a logical public health response to the HIV epidemic. Our findings suggest that acute HIV infection screening strategies, in our setting, are helpful for early diagnosis in men who have sex with men, in persons with seroconversion symptoms and in previously negative repeat testers.

A review of the impact of cost and quality of HIV kits on HIV testing in a Nigerian Teaching Hospital

Background: When HIV antibodies testing was introduced in Aminu Kano Teaching Hospital, Kano a couple of years ago, Double ELISA was used to test blood samples before a particular specimen was diagnosed as reactive or non-reactive. A time came when immunoconfirmatory test was introduced into HIV antibodies testing for confirmations of the presence of HIV. Objectives: This present retospective study is to review the impact of cost and quality of HIV reagent kits in the two periods A and B on the patients and confidence on the health care provider. Methods: We collated and compared laboratory records for both periods of HIV antibodies testing at Aminu Kano Teaching Hospital Kano consisting of period A from November 1997 to May 1998 (7 months) and period B from November 1998 to May 1999 (7months). In period A, double ELISA was used (Genie II and Immunocomb Bispot) while in period B, Immunocomb Bispot and Immunoconfirm II were used Results: The results show that the cost per test increased from two hundred and fifty Naira($2) to five hundred Naira($4). There was a reduction on the number of patients from 289 to 258 within the two periods. But the prevalence of reactive HIV antibodies decreased from 43.6% to 36.8%. Conclusion: The period when Immunoconfirmatory technique was introduced brought assurance, reliability and confidence to HIV diagnosis test in the centre.

Another look at Emergency Department HIV screening in practice: no need to revise expectations

BackgroundA recent study reported a lower than expected specificity and positive predictive value of the rapid oral HIV test in the setting of routine emergency department (ED) screening. These results appeared inconsistent with the findings in another urban Emergency Department during the same time period.ObjectiveTo compare the specificity and positive predictive vale (PPV) of an oral rapid HIV test used in an ED screening program in Washington DC with that performed in the USHER clinical trial.DesignPeriod cross-sectional analysis of rapid oral HIV testing conducted in an ongoing HIV screening program emergency department patients.SettingThe George Washington University Emergency Department (Washington DC) from 7 February to 1 October 2007.Patients1,560 adults seen in the ED for non-HIV-related presenting complaints, who participated in the HIV screening program.InterventionRapid HIV testing with the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test (OraSure Technologies, Bethlehem, Pennsylvania). Patients with reactive rapid test results were offered Western blot testing for confirmation.MeasurementsSpecificity and positive predictive value for the program were determined. Findings were compared to those found in the USHER trial.ResultsOf 1,560 patients screened for HIV, 13 [0.8%, 95% CI 0.38% to 1.28%] had a reactive HIV screening test, and all were confirmed to be positive by Western Blot. The specificity was 100% (95% CI 99.6%-100%).LimitationSince non-reactive tests were not confirmed, the test sensitivity cannot be determined.ConclusionReview of our data conflict with findings from the USHER study surrounding false positive OraQuick HIV screening. Our data suggest that rapid HIV screening protocols implemented in EDs outside of the clinical trial paradigm perform effectively without an excess of false positive results. Compared with other screening tests, HIV rapid screening should remain an essential component of ED practice.

Primary Meningococcal Arthritis as Initial Presentation in a Previously Undiagnosed HIV-Infected Patient

A 38-year-old African-American male complaining of pain in multiple joints was initially diagnosed with gouty arthritis concurrent with gonococcal septic arthritis. The diagnosis was made based on arthrocentesis results showing Gram-variable cocci and monosodium urate crystals in the synovial fluid. Final blood and synovial fluid cultures confirmed a diagnosis of primary septic arthritis caused by Neisseria meningitidis, serogroup X. Further evaluation revealed a reactive HIV antibody test with enzyme- linked immunoassay (ELISA) confirmed by western blot. His CD4 count was 36 cells/mm and viral load was >500,000 copies/mL. We present a case of primary meningococcal arthritis caused by N meningitidis serogroup X as the initial presentation of a patient with previously undiagnosed HIV.

Revising Expectations from Rapid HIV Tests in the Emergency Department

Expanded HIV screening efforts in the United States have increased the use of rapid HIV tests in emergency departments. The reported sensitivity and specificity of rapid HIV tests exceed 99%. To assess whether a reactive rapid oral HIV test result correctly identifies adults with HIV infection in the emergency department. Diagnostic test performance assessment within the framework of a randomized, clinical trial. Brigham and Women's Hospital emergency department (Boston, Massachusetts) from 7 February to 1 October 2007. 849 adults with valid rapid oral HIV test results. Rapid HIV testing with the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test (OraSure Technologies, Bethlehem, Pennsylvania). Patients with reactive rapid test results were offered enzyme-linked immunoassay, Western blot, and plasma HIV-1 RNA testing for confirmation. Specificity and positive likelihood ratio. 39 patients had reactive results (4.6% [95% CI, 3.2% to 6.0%]). On confirmation, 5 patients were HIV-infected (prevalence, 0.6% [CI, 0.1% to 1.1%]) and 26 were non-HIV-infected (8 patients declined confirmation). The estimated rapid test specificity was 96.9% (CI, 95.7% to 98.1%). Sensitivity analyses of the true HIV status of unconfirmed cases and test sensitivity resulted in a positive likelihood ratio of 8 to 32. Western blot alone as a confirmation test provided conclusive HIV status in only 50.0% (CI, 30.8% to 69.2%) of patients at first follow-up. The addition of HIV-1 RNA testing to the confirmation protocol improved this rate to 96.2% (CI, 88.8% to 100.0%). Test sensitivity cannot be assessed because nonreactive OraQuick test results were not confirmed. Although patients with a reactive oral OraQuick HIV screening test in the emergency department had an 8- to 32-fold increased odds of HIV infection compared with the pretest odds, the specificity of the test was lower than anticipated.

Protocols for Confirmation of Reactive Rapid HIV Tests

Protocols for Confirmation of Reactive Rapid HIV Tests

The significance of combining World Health Organization and Center for Disease Control criteria to resolve indeterminate human immunodeficiency virus type-1 Western blot results

A total of 466 repeatedly reactive HIV-1 blood samples evidenced by enzyme immunoassay were analyzed by the Western blot method and interpreted according to WHO and CDC criteria. Discordant and indeterminate samples were further analyzed by PCR. When the Western blot result was classified as indeterminate, according to both WHO and CDC criteria, the PCR test was always negative. These findings suggest that samples with double-indeterminate status should be reported as negative.

Cross-reactive CD8+ T cell epitopes identified in US adolescent minorities.

Vaccines designed to bring forth CD8+ T cell responses in different racial and ethnic groups will require inclusion of T cell epitopes presented by various MHC class I molecules. This study was designed to identify new CD8+ T cell epitopes in HIV-infected African American and Hispanic youth as well as to determine the frequency of responses to both novel and previously described HIV-1 epitopes in a cohort of racially and ethnically diverse individuals. We found 8 MHC class I-restricted CD8+ T cell epitopes that had not been previously described, another 8 epitopes that were restricted by class I alleles not previously associated with these epitopes, and 8 additional epitopes that have been described previously. In a larger cohort, we demonstrated that 11 (69%) of these 16 newly described immunogens were recognized by individuals of different race or ethnicity. Most HIV-1-specific CD8+ T cell epitopes identified were either novel or restricted by alternative MHC class I alleles. Frequent recognition of several of these CTL epitopes in persons of diverse racial backgrounds bodes well for the development of a broadly reactive HIV-1 vaccine.

Condiloma gigante de la vulva. Presentación de un caso

Summary The purpose of this report is to comment on the case of a 16 year-old nulliparous patient who presented to the gynaecolgy clinic in Kawabe General Hospital, Zambia. She had a past history of good health, but had noticed a rapid increase in the size of her external genitalia over a period of 6 to 12 months, which interfered with walking. On examination a large mass was observed in the vulva, almost occluding it, which had an irregular surface with striae in the form of cock´s crests and the characteristic odour of condyloma acuminata. Vaginal examination with a speculum was impossible. Blood tests showed reactive serology and HIV positive status. Following unsuccessful antibiotic and local antiviral treatment, simple vulvectomy was carried out in two stages, completely excising the tumour. There were no visible lesions of similar characteristics found in the vagina. Histological examination confirmed the clinical suspicion of giant condyloma acuminata of the vulva.

Viral levels in newborn African infants undergoing primary HIV-1 infection

We examined weekly changes in viral levels in seven untreated infants infected with HIV at birth. Viral levels spiked immediately but reverted quickly to plateau levels typical of infant HIV infection within 2 weeks of first detected viraemia. We speculated that the depletion of naive, susceptible cells is responsible for the rapid decrease in spike levels and that the rapid replacement of lymphocytes in infants causes the high plateau viral levels (10(5) copies/ml) to be sustained.

High concordance between polymerase chain reaction and antibody testing of specimens from individuals dually infected with HIV types 1 and 2 in Guinea-Bissau, West Africa.

In this study we have evaluated the concordance between serology, using five commercially available antibody assays designed to discriminate between HIV-1 and HIV-2, and the polymerase chain reaction (PCR) for the detection of HIV-1 and HIV-2 dual infection. Thirty-seven HIV-1 and HIV-2 dually reactive serum samples from individuals in Guinea-Bissau with total CD4+ T lymphocyte counts ranging from 9 to 948 x 10(6)/liter were included in the study. All samples were tested by Multispot, Pepti-LAV, and Immunocomb HIV-1 and HIV-2 discriminatory antibody assays. Thirty-two of the 37 samples were also tested by a combination of two HIV type-specific antibody enzyme-linked immunosorbent assays (ELISA; Wellcozyme HIV-1 and Murex HIV-2). Each sample showed dual reactivity in all or any of these assays. A nested PCR based on primer systems in the vif and pol regions of HIV-1 and in the gag and LTR regions of HIV-2 was used to evaluate the serological results. Thirty samples from HIV-1 antibody-positive individuals and 30 samples from HIV-2 antibody-positive individuals were all PCR positive with their corresponding primer systems. The type specificity was 100% for all of the primer systems. The concordance between dual HIV-1 and HIV-2 reactivity on the serological assays and PCR was 77.7% for Multispot, 80% for Pepti-LAV, 81.8% for Immunocomb, and 85.7% for the two ELISAs used in combination. Thus the majority of individuals included in this study appeared to be truly dually infected. The study shows that it is possible, through a careful selection of assays, to reach a high concordance between serological assays and PCR in studying HIV-1 and HIV-2 dual infections.