Recent HIV Infection Research Articles

P226 A year of ‘sex, steam and stis’

Background/introduction This sauna clinic was set up as recent HIV infection amongst MSM in our city is higher than the national average. Following a successful 6 month pilot, the clinic was commissioned for another year. Aim(s)/objectives Provide accessible, convenient sexual healthcare/promotion for ‘hard-to-reach’ individuals. Promote regular STI testing amongst this high-risk group. Assess measurable outcomes to determine the service’s success. Methods A weekly nurse-led clinic was set up at the sauna. Rectal, pharyngeal and urine testing for chlamydia and gonorrhoea were offered, with HIV, hepatitis B/C and syphilis testing and Hepatitis B vaccination. Identified infections were treated at the sauna clinic or our GUM clinic. Results 231 new/rebook episodes over 57 clinics. 80% had previously accessed sexual health services but only 63% had previously undergone extra-genital sampling. HIV testing uptake was 96%. 16% had never tested for HIV; 22% last tested over a year ago. 20% reported sex with men and women. 18% had at least one of chlamydia, gonorrhoea, HIV or syphilis identified, compared with 14% amongst asymptomatic MSM attending our GUM clinic. 80% of chlamydia and gonorrhoea infections identified were purely extra-genital. 6 new HIV diagnoses were made, 4 of which were recently acquired HIV. HIV prevalence was 3%. Discussion/conclusion The service has been continually modified to optimise attendance. A new initiative introduced by the sauna management team includes discounted sauna entry for clients attending the sauna clinic. This clinic’s success has been due to close partnership and collaboration between NHS, third sector, private sector and local commissioners.

Frequency of coreceptor tropism in PBMC samples from HIV-1 recently infected blood donors by massively parallel sequencing: the REDS II study

BackgroundThe interaction of HIV-1 and target cells involves sequential binding of the viral gp120 Env protein to the CD4 receptor and a chemokine co-receptor (either CCR5 or CXCR4). CCR5 antagonists have proved to be an effective salvage therapy in patients with CCR5 using variants (R5) but not with variants capable of using CXCR4 (×4) phenotype. Thus, it is critically important to determine cellular tropism of a country’s circulating HIV strains to guide a management decision to improve treatment outcome. In this study, we report the prevalence of R5 and ×4 HIV strains in 45 proviral DNA massively parallel sequencing “MPS” data from recently infected Brazilian blood donors.MethodsThe MPS data encompassing the tropism-related V3 loop region of the HIV‐1 env gene was extracted from our recently published HIV-1 genomes sequenced by a paired-end protocol (Illumina). HIV‐1 tropism was inferred using Geno2pheno[coreceptor] algorithm (3.5 % false-positive rate). V3 net charge and 11/25 rules were also used for coreceptor prediction.ResultsAmong the 45 samples for which tropism were determined, 39 were exclusively R5 variants, 5 ×4 variants, and one dual-tropic or mixed (D/M) populations of R5 and ×4 viruses, corresponding to 86.7, 11.1 and 2.2 %, respectively. Thus, the proportion of all blood donors that harbor CXCR4-using virus was 13.3 % including individuals with D/M-tropic viruses.ConclusionsThe presence of CCR5-tropic variants in more than 85 % of our cohort of antiretroviral-naïve blood donors with recent HIV-1 infection indicates a potential benefit of CCR5 antagonists as a therapeutic option in Brazil. Therefore, determination of viral co-receptor tropism is an important diagnostic prerequisite.

Longitudinal trends of recent HIV-1 infections in Slovenia (1986-2012) determined using an incidence algorithm.

Resolving dilemma whether the rise in the number of HIV diagnoses represents an actual increase in HIV transmissions or is a result of improved HIV surveillance is crucial before implementing national HIV prevention strategies. Annual proportions of recent infections (RI) among newly diagnosed persons infected with HIV-1 in Slovenia during 27 years (1986-2012) were determined using an algorithm consisting of routine baseline CD4 and HIV viral load measurements and the Aware BED EIA HIV-1 Incidence Test (BED test). The study included the highest coverage of persons diagnosed with HIV during the entire duration of an HIV epidemic in a given country/region (71%). Out of 416 patients, 170 (40.9%) had a baseline CD4 cell count less than 200 cells/mm(3) and/or HIV-1 viral load less than 400 copies/ml and were characterized as having a long-standing infection (LSI). The remaining 246 patients were additionally tested using the BED test. Overall, 23% (97/416) of the patients were labeled RI. The characteristics significantly associated with RI were as follows: younger age, acute retroviral syndrome, CDC class A and other than C, no AIDS defining illnesses, HIV test performed in the past, a higher viral load, and a higher CD4 cell count. An interesting trend in the proportion of RI was observed, with a peak in 2005 (47% of RI) and the lowest point in 2008 (12%) in parallel with a rise in the numbers of new HIV diagnoses. This study could help promote the idea of introducing periodic HIV incidence monitoring using a simple and affordable algorithm.

High HIV prevalence and incidence among MSM across 12 cities in India.

To characterize prevalence, incidence, and associated correlates of HIV infection among MSM in 12 cities across India. Cross-sectional sample using respondent-driven sampling from September 2012 to June 2013. A total 12022 MSM (~1000/city) were recruited. Participants had to be at least 18 years, self-identify as male, and report oral/anal intercourse with a man in the prior year. HIV infection was diagnosed using three rapid tests. Cross-sectional HIV incidence was estimated using a multiassay algorithm. All estimates incorporate respondent-driven sampling-II weights. Median age was 25 years, 45% self-identified as 'panthi' (predominantly penetrative anal intercourse) and 30.6% reported being married to a woman. Weighted HIV prevalence was 7.0% (range: 1.7-13.1%). In multivariate analysis, significantly higher odds of HIV infection was observed among those who were older, had lower educational attainment, were practicing purely receptive anal sex or both receptive and penetrative sex, and those who were herpes simplex virus-2 positive. Of 1147 MSM who tested HIV positive, 53 were identified as recent HIV infections (annualized incidence = 0.87%; range = 0-2.2%). In multivariate analysis, injecting drugs in the prior 6 months, syphilis, and higher number of male partners and fewer female partners were significantly associated with recent HIV infection. We observed a high burden of HIV among MSM in India with tremendous diversity in prevalence, incidence, and risk behaviors. In particular, we observed high incidence in areas with relatively low prevalence suggesting emerging epidemics in areas not previously recognized to have high HIV burden.

Development of an avidity assay for detection of recent HIV infections

HIV avidity can measure the incidence of recent infections within the population. The aim of this study was to evaluate an HIV avidity assay, initially from a clinically defined group of patients and then apply the assay to a prospective study to determine the false recency rate and mean duration of recency for the assay. The assay is a commercial ELISA modified with 7M urea. The validation of the assay used plasma from patients split into Group 1 (recently infected N=25) and group 2 (established infection N=301). The prospective study tested 178 newly diagnosed HIV patients for avidity. A total of 326 retrospective samples of known HIV status were collected and tested. The initial evaluation gave a sensitivity 100% (CI 86.16–100%) and specificity of 98.65% (95% CI 97.05–99.78%). The prospective study incorporating 178 newly diagnosed patients found 22 patients with low avidity. Follow-up samples obtained from low avidity patients determined the estimated mean duration of recency to be between 3 and 4 months with a false recency rate of 0.89% (CI: 0.24–2.3%). The assay described here compares well in sensitivity, specificity and false recency rate with that of other published avidity assays.

Case Report: Pulmonary Nocardiosis in a Patient with Chronic Obstructive Pulmonary Disease and Receiving Corticosteroid Treatment due to Nephrotic Syndrome.

Introduction : Nocardia spp. belong to Actinomycetes family and usually found in soil. They show variation in acid fast stain. Microscobic examination reveals Gram positive filamentous bacilli. Nocardiosis, is a rare clinical situation caused by Nocardia species and takes place especially in immunosuppressed individuals. In our case report we aimed to present pulmonary nocardiosis in a patient receiving corticosteroid treatment due to nephrotic syndrome and also accompanying chronic obstructive pulmonary disease. Case Presentation : 53 year old male patient was admitted to the Chest Diseases outpatient clinic with fever, sputum and cough complaints. The patient had a previous story of nephrotic syndrome and chronic obstructive pulmonary disease and receiving corticosteroid treatment. Thorax CT image showed a 13 cm cavitary lesion at the lower lobe of the right lung, and 21 mm lesion neighboring to the other lesion. Fibrotic structure was detected on both hilus of the lung. This was evaluated as a sequela of infection. The patient underwent flexible bronchoscopy and respiratory tract specimens (bronchoalveolar lavage, bronchial lavage and sputum) were sent to the Microbiology Laboratory. The Gram stain showed filamentous Gram positive bacilli and on the fourth day of incubation Nocardia spp was reported. The patient was administered trimethoprim sulfamethoxazole treatment and recovered. Discussion : Pulmonary nocardiosis is a rare disease. The importance of this infectious pathogen has increased due to recent increase immunosuppressive treatment modalities, HIV infection, and organ transplantation. The clinical and radiological symptoms are nonspecific and because of this microbiological methods are important in diagnosis of nocardiosis. Consecutive examination of clinical material showing the typical microscopic appearance in these patients should draw the attention of the clinician to this pathogen and treatment is needed to be done accordingly.

Correlates of HIV Transmission from Husband to Wife among Heterosexual Married Couples in ART-era in West Bengal, India

Objective: To identify factors associated with HIV-transmission from husbands to their wives within the existing HIV prevention and control program environment in West Bengal, India. Methods: In this cross-sectional study, information was collected from the study participants on socio-demography and various health issues including sexually transmitted diseases (STDs). They were also tested for blood borne and sexually transmitted infections. Women living with HIV were compared for behavioral and biologic markers against women who did not have the virus. Both these groups of women were married to HIV sero-reactive men. To detect recent HIV infection, HIV sero-negative women were tested by Polymerase Chain Reaction. Results: Of the 234 married couples, 29% (69/234) lived in HIV discordant relationship where wives were not infected with HIV and the rest were concordant for HIV infection. Six of the 165 women living in concordant relationship acquired HIV infection recently. Fifty six percent of the husbands were in advanced stage of HIV disease with CD4 count ≤200/μl while tested for the first time at ART center. Factors independently associated with HIV concordance were 'wives experiencing any STD-symptom after marriage' (Adjusted Odds Ratio (AOR) 2.05; 95% CI 1.09 - 3.83; p=0.02) and 'self-reported male condom use/reduced frequency of sex with spouse' (AOR 2.99; 95% CI 1.29-6.94; p=0.01). Although 'HSV-2 concordance' (Odds Ratio (OR) 2.46; 95% CI 1.32-4.59; p=0.004) and 'bacterial vaginosis' (OR 2.57; 95% CI 1.18-5.61; p=0.02) were associated with HIV infection in wives in uni-variate analyses, the strength of such associations weakened in multi-variate model. ART intake by husbands did not offer any protection against HIV infection in wives. Conclusions: Early initiation of ART among HIV discordant couples, strengthening of STD prevention and control and limitation of self-reported sexual risk reduction to inform HIV-program in India are underscored.

Seroincidence of HIV and prevalence of transmitted drug resistance of HIV-1 strains among persons seeking voluntary counselling and testing in Taiwan.

IntroductionThe total case number of persons who are newly diagnosed with HIV continues to increase in Taiwan and men who have sex with men (MSM) have re-emerged as the leading risk group for HIV transmission. In this study, we aimed to estimate the incidence rate of HIV infection among those individuals who sought voluntary counselling and testing (VCT) service at a university hospital.MethodsBetween 1 April, 2006 and 31 December, 2013, 18,246 tests for HIV antibody were performed among 12143 individuals at the VCT service. A total of 2157 individuals who tested negative for anti-HIV antibody had subsequent follow-up tests at the same VCT service, which composed the study population for estimation of incidence rate of recent HIV infection. The BED assays were used to identify recent HIV infections that occurred within the previous six months before seeking VCT service.ResultsDuring the 6.5-year study period, 647 individuals were diagnosed as being HIV-positive, with an overall HIV seroprevalence of 3.55% (95% CI 3.27–3.82). The overall incidence rate of HIV infection was estimated 4.13 per 100 person-years of follow-up (95% CI 3.67–4.69 per 100 person-years of follow-up). MSM had an estimated 10-fold higher seroprevalence and seroincidence of HIV than heterosexuals. Of 647 clients testing positive for HIV, 603 clients were MSM (93.2%) and 477 patients (70.8%) subsequently sought HIV care at the hospital; 226 (47.4%) were diagnosed as having recent HIV infections by the BED assay, while 244 (51.2%) long-term infection and 7 without data by the BED assay. Of those patients, 173 (75.6%) and 178 patients (73.0%) with recent HIV infection and long-term infection had data of transmitted drug resistance mutations, respectively. The prevalence of transmitted drug resistance mutations to any class of antiretroviral therapy was 9.0% and 10.6% (p=0.68), respectively, of the HIV-1 strains from the patients with recent HIV infection and long-term infection, respectively.ConclusionsThe seroincidence rate of HIV among persons seeking VCT was estimated 4.13 per 100 person-years of follow-up. The prevalence of transmitted drug resistance to any class of antiretroviral agents was similar between those who were recently infected with HIV and those who had long-term infection in Taiwan.

Analysis of transmitted drug resistance and HIV-1 subtypes using dried serum spots of recently HIV-infected individuals in 2013 in Germany.

IntroductionThe Robert Koch Institute (RKI) aimed to assess a molecular surveillance strategy based on filter-dried serum spots (DSS) of all newly diagnosed HIV infections in Germany. In 2013, diagnostic laboratories sent DSS to the RKI representing 55% of the newly diagnosed HIV infections reported to the RKI (protection against infection act). DSS were first tested serologically to identify recently acquired infections (<140 days duration of infection); those classified as “recent infection” were processed for HIV-1 genotyping. The aim of this study was to assess the level of TDR and the current HIV-1 subtypes in the main HIV transmission group categories (TrGrpC) in 2013: men who have sex with men (MSM), women/men with heterosexual contacts (HET) and injecting drug users (IDUs).Materials and MethodsDSS were tested for recency of infection using the BED capture EIA. Viral RNA from “recent infections” was amplified by HIV-1 group M generic pol-RT-PCR covering all resistance-associated positions in the HIV-1 protease (AS1-99) and reverse transcriptase (AS1-252) if viral loads were ≥6,500 copies/mL. PCR amplicons were sequenced (Sanger) to analyze genotypic resistance and the HIV-1 subtype. Results were merged to data from the HIV report, i.e. the TrGrpC.ResultsIn 2013, 1027 DSS were classified as recent HIV infections (506 MSM, 118 HET, 31 IDUs, 6 others, 366 unknown). RNA was extracted from 703 recent cases and 389/503 samples with sufficient viral load were PCR-positive. By June 2014, 276/389 samples were sequenced: TDR was identified in 13% (35/276) of the recent infections including single (PI, NRTI, NNRTI) and dual drug class resistant strains (NRTI/NNRTI; NNRTI/PI). 18% (51/276) of recent HIV-1 infections were caused by non-B subtypes (A1, C, CRF01_AE, CRF02_AG, D, F, G, URFs). TDR was observed at comparable levels in all TrGrpC. Proportions of non-B infections were significantly higher in HET (78%; 14/18) and IDUs (60%; 3/5) compared to MSM (8%; 14/169) (p<0.01).ConclusionsThe proportion of TDR was similar but the proportion of HIV-1 subtype non-B infections was higher as previously described for Germany based on results from the German HIV-1 Seroconverter Cohort [1,2]. This difference could be the result of a broadened inclusion of HET and IDUs due to the sampling method used making this study representative for molecular surveillance of HIV-1 in Germany.

Treatment outcome in HIV+ patients receiving 3- or 4-drug regimens during PHI.

IntroductionThe optimal timing and modality of therapeutic intervention during early phases of HIV infection is still debated; in our prospective observational study we evaluated immunological and virological outcome in HIV+ patients treated during acute or recent HIV infection.Materials and MethodsA total of 25 naïve patients with acute (detectable HIV-RNA, immature Western Blot) or recent (documented infection within six months) HIV infection were recruited at the Infectious Diseases Units of the University of Milan and Turin from 2009 to 2014. Patients received treatment with two NRTIs+one NNRTI/bPI, with or without an induction phase with an additional fourth drug (raltegravir or maraviroc) until HIV-RNA undetectability maintained for six months. Blood samples for HIV-RNA, lymphocyte subsets and tropism assessment were obtained at the beginning of the treatment (BL). Patients underwent subsequent six-monthly follow up for clinical outcome, CD4 cell count and HIV-RNA up to 18 months.ResultsMedian increase in CD4 cells from 0 to 12 months was greater in patients treated during acute (n=18) versus recent (n=7) infection [284/µL, IQR (227–456) versus 176/µL, IQR (70–235); Mann-Whitney test, p=0.046]. This higher value was maintained through 18 months, although failing to reach statistical significance. Patients with acute or recent infection did not significantly differ in virological success (83.3% versus 85.7% at 12 months). We considered CD4 cells gains at six months (multivariate analysis, ANCOVA; Figure 1) and detected an inverse correlation with CD4 levels at BL (r=−0.517; p=0.008) and a direct correlation with the status of acute infection (r=0.234, p NS). This last correlation reached statistical significance at 12 months (r=0.418, p=0.035), whereas the inverse correlation with CD4 levels at BL was still present without a statistical significance (r=−0.350; p=0.072). Patients treated with three or four drugs did not show any significant difference in immunological nor virological response (Mann-Whitney and χ2 test). Modification or interruption of therapy for tolerability took place in 4 out of 25 patients, all while receiving four drugs; two patients underwent STI between 12 and 18 months following virological success.ConclusionsTreatment of primary infection appeared to be effective in preserving the pool of CD4 cells in acute more than recent infection. There was no evidence of a different outcome through the addition of a fourth drug to the standard treatment.

Longitudinal analysis of HIV-1-specific antibody responses.

Laboratory assays for determining recent HIV-1 infection are of great public health importance for aiding in the estimation of HIV incidence. Concerns have been raised about the potential for misclassification with serology-based assays due to fluctuations in the antibody response, particularly following progression to AIDS. We characterized longitudinal antibody responses to HIV using a cohort of men who have sex with men (MSM) sampled for up to 17 years, in which 57% of the 65 study subjects included in the current analyses progressed to AIDS during the study period. Envelope-specific total IgG antibody levels, avidity, and p24-specific IgG3 levels were evaluated using a multiplexed Bio-Plex assay. For the majority of the analytes, no significant difference in IgG reactivity was observed between AIDS and non-AIDS specimens. Although a slight decline in gp120 reactivity was noted with decreasing CD4(+) T cell count, the drop in assay values was relatively minimal and would likely not lead to an increase in the misclassification rate of the assay. A peak in HIV-1 p24 IgG3 levels was observed during early infection, as confirmed by testing 1,216 specimens from 342 recent seroconverters with the Bio-Plex assay. As expected, IgG3 reactivity declined with disease progression and decreasing CD4(+) T cell count in the MSM cohort; however, 37% of the study subjects exhibited relatively high IgG3 levels late in the course of infection.

Settings, Sexual Practices, and Personal HIV Protection Strategies: The Circumstances of Recent HIV Infections in Switzerland

The authors investigated the circumstances of recent HIV infections in Switzerland. Their aim was to identify the interactions between individuals’ personal HIV protection strategies, their actual risk behavior, and situational factors during the high-risk event. Semi-structured interviews were conducted with 32 recently infected persons aged 21–64. Data analysis followed the principles of Grounded Theory. Interviews revealed that respondents adopted the safer sex strategy, risk reduction strategies, a priori ineffective HIV protection strategies, and alternating HIV protection strategies. Some, however, adopted no explicit protection strategy. Risk reduction strategies mirrored discourses circulating within men who have sex with men subcultures as well as messages about noninfectiousness while on treatment. Safer sex had failed due to situational or relational factors. In the case of the other strategies, infections resulted from the risk inherent in these strategies. Results show the influence of discourses about risk reduction strategies and noninfectiousness under antiretroviral treatment on personal HIV protection strategies.

Geographic Utilization of Gift Cards Used for Financial Incentives to Encourage Viral Suppression: Findings from HPTN 065

in the study: one elected to be treated at a non-study clinic, two had psychiatric problems that precluded enrollment, 5 refused to participate due to logistics and other reasons, and we were unable to recontact 1. Slightly over half of the HIV-infected participants were linked to care within 7 days of HIV diagnosis. Conclusions: Detection of acute and recent HIV infection and rapid linkage to care is possible. Successful linkage of such individuals to HIV care including ART can maximize TasP intervention and individual clinical benefits. This approach may be important for future cure strategies.

Characteristics of patients recently infected with HIV-1 non-B subtypes in France: a nested study within the mandatory notification system for new HIV diagnoses.

The presence of HIV-1 non-B subtypes in Western Europe is commonly attributed to migration of individuals from non-European countries, but the possible role of domestic infections with non-B subtypes is not well investigated. The French mandatory anonymous reporting system for HIV is linked to a virological surveillance using assays for recent infection (<6 months) and serotyping. During the first semester of years 2007 to 2010, any sample corresponding to a non-B recent infection was analyzed by sequencing a 415-bp env region, followed by phylogenetic analysis and search for transmission clusters. Two hundred thirty-three recent HIV-1 infections with non-B variants were identified. They involved 5 subtypes and 7 circulating recombinant forms (CRFs). Ninety-two cases (39.5%) were due to heterosexual transmissions, of which 39 occurred in patients born in France. Eighty-five cases (36.5%) were identified in men having sex with men (MSM). Forty-three recent non-B infections (18.5%) segregated into 14 clusters, MSM being involved in 11 of them. Clustered transmission events included 2 to 7 cases per cluster. The largest cluster involved MSM infected by a CRF02_AG variant. In conclusion, we found that the spread of non-B subtypes in France occurs in individuals of French origin and that MSM are particularly involved in this dynamic.

Diagnostic technologies in practice: gay men's narratives of acute or recent HIV infection diagnosis.

Diagnosing HIV-positive gay men through enhanced testing technologies that detect acute HIV infection (AHI) or recent HIV infection provides opportunities for individual and population health benefits. We recruited 25 men in British Columbia who received an acute (n = 13) or recent (n = 12) HIV diagnosis to engage in a longitudinal multiple-methods study over one year or longer. Our thematic analysis of baseline qualitative interviews revealed insights within men’s accounts of technologically mediated processes of HIV discovery and diagnosis. Our analysis illuminated the dialectic of new HIV technologies in practice by considering the relationship between advances in diagnostics (e.g., nucleic acid amplification tests) and the users of these medical technologies in clinical settings (e.g., clients and practitioners). Technological innovations and testing protocols have shifted experiences of learning of one’s HIV-positive status; these innovations have created new diagnostic categories that require successful interpretation and translation to be rendered meaningful, to alleviate uncertainty, and to support public health objectives.

Analysis on hepatitis C virus infection and related factors among newly reported HIV infections in Henan province

To study hepatitis C virus infection and related factors among newly reported HIV infections in Henan province. Both HIV-1 BED incidence and anti-HCV tests were applied on newly reported HIV-1 infections between 1 Jul. 2012 to 30 Jun. 2013 in Henan province. 2049 HIV-1 infections were newly reported between 1 July 2012 to 30 June 2013 in Henan province, with the positive rate of anti-HCV as 14.87% (271/1 887) and the proportion of BED positives was 26.34% (497/1 887). The recent HIV-1 infections appeared lower HCV prevalence than non-recent HIV-1 infection. Among 20-39 age group, HIV-1 infections had a lower HCV prevalence than among the other age groups. Patients carrying HIV-1 through injecting drug use showed higher HCV prevalence. Under results on BED; age, infection route and area were influencing factors of HCV prevalence in newly reported HIV-1 infections in Henan province, suggesting that corresponding prevention programs should be targeted.

Diagnosing HIV in Switzerland

The diagnosis "HIV infection" has severe consequences. False positive or false negative HIV results must be avoided. The Swiss Federal Office of Public Health generated a concept for HIV testing which also includes the characterization of HIV for optimal medical care of the HIV-infected patient. This concept requests that the following four questions are answered: 1. Is the patient indeed HIV-infected? 2. Is it HIV-1 or HIV-2, and if the patient is tested positive for HIV-1, what group, M or O? Are drug resistances present? 3. What is the HIV copy number in the blood? 4. What is the percentage of recent HIV-infections (< 12 months) among all tested positive test results? We also present a short summary how to approach the HIV-infected patient at the initial and subsequent visits.

Evaluation of an antibody avidity index method for detecting recent human immunodeficiency virus type 1 infection using an automated chemiluminescence immunoassay

BackgroundRecent infection testing algorithms (RITAs) are used in public health surveillance to estimate the incidence of recently acquired HIV-1 infection. ObjectivesOur aims were (i) to evaluate the precision of the VITROS® Anti-HIV 1+2 automated antibody avidity assay for qualitative detection of antibodies to HIV 1+2 virus; (ii) to validate the accuracy of an automated guanidine-based antibody avidity assay to discriminate between recent and long standing infections using the VITROS 3600 platform; (iii) to compare this method with BED-CEIA assay; and (iv) to evaluate the occurrence of false recent misclassifications by the VITROS antibody avidity assay in patients with a CD4 count <200cells/μL and in patients on combination antiretroviral therapy (cART). ResultsThe VITROS® antibody avidity assay is highly reproducible. The ROC curve analysis of the accuracy of this assay, optimized for sensitivity and specificity, had an AI cut off of ≤0.51, with sensitivity and specificity values of 86.67% (95% CI: 72.51–94.46) and 86.24% (95% CI: 78.00–91.84), respectively. The agreement between VITROS antibody avidity and BED-CEIA assays was good. Misclassifications of long standing infections as recent infection occurred in 8.2% of patients with CD4 <200cell/μL and 8.7% in patients on combination antiretroviral therapy. ConclusionsThe VITROS antibody avidity assay is a reliable serological method to detect recent HIV-1 infections and it could be incorporated into a RITA to estimate HIV incidence.

A comparison of two measures of HIV diversity in multi-assay algorithms for HIV incidence estimation.

BackgroundMulti-assay algorithms (MAAs) can be used to estimate HIV incidence in cross-sectional surveys. We compared the performance of two MAAs that use HIV diversity as one of four biomarkers for analysis of HIV incidence.MethodsBoth MAAs included two serologic assays (LAg-Avidity assay and BioRad-Avidity assay), HIV viral load, and an HIV diversity assay. HIV diversity was quantified using either a high resolution melting (HRM) diversity assay that does not require HIV sequencing (HRM score for a 239 base pair env region) or sequence ambiguity (the percentage of ambiguous bases in a 1,302 base pair pol region). Samples were classified as MAA positive (likely from individuals with recent HIV infection) if they met the criteria for all of the assays in the MAA. The following performance characteristics were assessed: (1) the proportion of samples classified as MAA positive as a function of duration of infection, (2) the mean window period, (3) the shadow (the time period before sample collection that is being assessed by the MAA), and (4) the accuracy of cross-sectional incidence estimates for three cohort studies.ResultsThe proportion of samples classified as MAA positive as a function of duration of infection was nearly identical for the two MAAs. The mean window period was 141 days for the HRM-based MAA and 131 days for the sequence ambiguity-based MAA. The shadows for both MAAs were <1 year. Both MAAs provided cross-sectional HIV incidence estimates that were very similar to longitudinal incidence estimates based on HIV seroconversion.ConclusionsMAAs that include the LAg-Avidity assay, the BioRad-Avidity assay, HIV viral load, and HIV diversity can provide accurate HIV incidence estimates. Sequence ambiguity measures obtained using a commercially-available HIV genotyping system can be used as an alternative to HRM scores in MAAs for cross-sectional HIV incidence estimation.

Intensified ART for Patients with Acute or Recent HIV Infection

Starting antiretroviral therapy (ART) in early HIV infection may result in a smaller viral burden in the latently infected pool. To understand whether intensifying ART in early infection leads to improved virologic and immunologic outcomes, investigators (with partial industry funding) conducted an open-label, randomized trial comparing standard boosted protease inhibitor (PI) therapy (tenofovir/FTC + boosted atazanavir or darunavir) with the same regimen plus raltegravir and maraviroc. Of 40 enrollees, 26 were randomized to five-drug ART and 14 to standard …