False-Positive Human Immunodeficiency Virus Enzyme Immunoassay Results in Pregnant Women

Objective: Examine whether false-positive HIV enzyme immunoassay (EIA) test results occur more frequently among pregnant women than among women who are not pregnant and men (others). Design: To obtain a large number of pregnant women and others tested for HIV, we identified specimens tested at a national laboratory using Genetic Systems HIV-1/HIV-2 Plus O EIA from July 2007 to June 2008. Methods: Specimens with EIA repeatedly reactive and Western blot-negative or indeterminate results were considered EIA false-positive. We compared the false-positive rate among uninfected pregnant women and others, adjusting for HIV prevalence. Among all reactive EIAs, we evaluated the proportion of false-positives, positive predictive value (PPV), and Western blot bands among indeterminates, by pregnancy status. Results: HIV prevalence was 0.06 % among 921,438 pregnant women and 1.34 % among 1,103,961 others. The false-positive rate was lower for pregnant women than others (0.14 % vs. 0.21%, odds ratio 0.65 [95 % confidence interval 0.61, 0.70]). Pregnant women with reactive EIAs were more likely than others (p,0.01) to have Western blot-negative (52.9 % vs. 9.8%) and indeterminate results (17.0 % vs. 3.7%) and lower PPV (30 % vs. 87%). The p24 band was detected more often among pregnant women (p,0.01). Conclusions: False-positive HIV EIA results were rare and occurred less frequently among pregnant women than others

Investing in the future: lessons learnt from communicating the results of HSV/ HIV intervention trials in South Africa

<p>Abstract</p> <p>Background</p> <p>Communicating the results of randomised controlled trials may present challenges for researchers who have to work with communities and policy-makers to anticipate positive outcomes, while being aware that results may show no effect or harm.</p> <p>Methods</p> <p>We present a case study from the perspective of researchers in South Africa about the lessons learnt from communicating the results of four trials evaluating treatment for herpes simplex virus type 2 (HSV-2) as a new strategy for HIV prevention.</p> <p>Results</p> <p>We show that contextual factors such as misunderstandings and mistrust played an important role in defining the communications response. Use of different approaches in combination was found to be most effective in building understanding, credibility and trust in the research process. During the communication process, researchers acted beyond their traditional role of neutral observers and became agents of social change. This change in role is in keeping with a global trend towards increased communication of research results and presents both opportunities and challenges for the conduct of future research.</p> <p>Conclusions</p> <p>Despite disappointing trial results which showed no benefit of HSV-2 treatment for HIV prevention, important lessons were learnt about the value of the communication process in building trust between researchers, community members and policy-makers, and creating an enabling environment for future research partnerships.</p

Circumcision of Male Children for Reduction of Future Risk for HIV: Acceptability among HIV Serodiscordant Couples in Kampala, Uganda

The ultimate success of medical male circumcision for HIV prevention may depend on targeting male infants and children as well as adults, in order to maximally reduce new HIV infections into the future.We conducted a cross-sectional study among heterosexual HIV serodiscordant couples (a population at high risk for HIV transmission) attending a research clinic in Kampala, Uganda on perceptions and attitudes about medical circumcision for male children for HIV prevention. Correlates of willingness to circumcise male children were assessed using generalized estimating equations methods.318 HIV serodiscordant couples were interviewed, 51.3% in which the female partner was HIV uninfected. Most couples were married and cohabiting, and almost 50% had at least one uncircumcised male child of ≤18 years of age. Overall, 90.2% of male partners and 94.6% of female partners expressed interest in medical circumcision for their male children for reduction of future risk for HIV infection, including 79.9% of men and 87.6% of women who had an uncircumcised male child. Among both men and women, those who were knowledgeable that circumcision reduces men's risk for HIV (adjusted prevalence ratio [APR] 1.34 and 1.14) and those who had discussed the HIV prevention effects of medical circumcision with their partner (APR 1.08 and 1.07) were significantly (p≤0.05) more likely to be interested in male child circumcision for HIV prevention. Among men, those who were circumcised (APR 1.09, p = 0.004) and those who were HIV seropositive (APR 1.09, p = 0.03) were also more likely to be interested in child circumcision for HIV prevention.A high proportion of men and women in Ugandan heterosexual HIV serodiscordant partnerships were willing to have their male children circumcised for eventual HIV prevention benefits. Engaging both parents may increase interest in medical male circumcision for HIV prevention

How community ART delivery may improve HIV treatment outcomes: Qualitative inquiry into mechanisms of effect in a randomized trial of community-based ART initiation, monitoring and re-supply (DO ART) in South Africa and Uganda

INTRODUCTION: UNAIDS fast track targets for ending the AIDS epidemic by 2030 call for viral suppression in 95% of people using antiretroviral therapy (ART) to treat HIV infection. Difficulties in linking to care following a positive HIV test have impeded progress towards meeting treatment targets. Community-based HIV services may reduce linkage barriers and have been associated with high retention and favourable clinical outcomes. We use qualitative data from The Delivery Optimization of Antiretroviral Therapy (DO ART) Study, a three-arm randomized trial of community ART initiation, monitoring and re-supply conducted in western Uganda and KwaZulu-Natal South Africa, to identify mechanisms through which community ART delivery may improve treatment outcomes, defined as viral suppression in people living with HIV (PLHIV). METHODS: We conducted open-ended interviews with a purposeful sample of 150 DO ART participants across study arms and study sites, from October 2016 to November 2019. Interviews covered experiences of: (1) HIV testing; (2) initiating and refilling ART; and (3) participating in the DO ART Study. A combined inductive content analytic and thematic approach was used to characterize mechanisms through which community delivery of ART may have contributed to viral suppression in the DO ART trial. RESULTS: The analysis yielded four potential mechanisms drawn from qualitative data representing the perspectives and priorities of DO ART participants. Empowering participants to schedule, re-schedule and select the locations of community-based visits via easy phone contact with clinical staff is characterized as flexibility. Integration refers to combining the components of clinic-based visits into single interaction with a healthcare provider. Providers" willingness to talk at length with participants during visits, addressing non-HIV as well as HIV-related concerns, is termed "a slower pace". Finally, increased efficiency denotes the time savings and increased income-generating opportunities for participants brought about by delivering services in the community. CONCLUSIONS: Understanding the mechanisms through which HIV service delivery innovations produce an effect is key to transferability and potential scale-up. The perspectives and priorities of PLHIV can indicate actionable changes for HIV care programs that may increase engagement in care and improve treatment outcomes

The Evaluation of a Rapid In Situ HIV Confirmation Test in a Programme with a High Failure Rate of the WHO HIV Two-Test Diagnostic Algorithm

BACKGROUND: Concerns about false-positive HIV results led to a review of testing procedures used in a Médecins Sans Frontières (MSF) HIV programme in Bukavu, eastern Democratic Republic of Congo. In addition to the WHO HIV rapid diagnostic test algorithm (RDT) (two positive RDTs alone for HIV diagnosis) used in voluntary counselling and testing (VCT) sites we evaluated in situ a practical field-based confirmation test against western blot WB. In addition, we aimed to determine the false-positive rate of the WHO two-test algorithm compared with our adapted protocol including confirmation testing, and whether weakly reactive compared with strongly reactive rapid test results were more likely to be false positives. METHODOLOGY/PRINCIPAL FINDINGS: 2864 clients presenting to MSF VCT centres in Bukavu during January to May 2006 were tested using Determine HIV-1/2 and UniGold HIV rapid tests in parallel by nurse counsellors. Plasma samples on 229 clients confirmed as double RDT positive by laboratory retesting were further tested using both WB and the Orgenics Immunocomb Combfirm HIV confirmation test (OIC-HIV). Of these, 24 samples were negative or indeterminate by WB representing a false-positive rate of the WHO two-test algorithm of 10.5% (95%CI 6.6-15.2). 17 of the 229 samples were weakly positive on rapid testing and all were negative or indeterminate by WB. The false-positive rate fell to 3.3% (95%CI 1.3-6.7) when only strong-positive rapid test results were considered. Agreement between OIC-HIV and WB was 99.1% (95%CI 96.9-99.9%) with no false OIC-HIV positives if stringent criteria for positive OIC-HIV diagnoses were used. CONCLUSIONS: The WHO HIV two-test diagnostic algorithm produced an unacceptably high level of false-positive diagnoses in our setting, especially if results were weakly positive. The most probable causes of the false-positive results were serological cross-reactivity or non-specific immune reactivity. Our findings show that the OIC-HIV confirmation test is practical and effective in field contexts. We propose that all double-positive HIV RDT samples should undergo further testing to confirm HIV seropositivity until the accuracy of the RDT testing algorithm has been established at programme level

Serum albumin and osmolality inhibit Bdellovibrio bacteriovorus predation in human serum

We evaluated the bactericidal activity of Bdellovibrio bacteriovorus, strain HD100, within blood sera against bacterial strains commonly associated with bacteremic infections, including E. coli, Klebsiella pneumoniae and Salmonella enterica. Tests show that B. bacteriovorus HD100 is not susceptible to serum complement or its bactericidal activity. After a two hour exposure to human sera, the prey populations decreased 15- to 7,300-fold due to the serum complement activity while, in contrast, the B. bacteriovorus HD100 population showed a loss of only 33%. Dot blot analyses showed that this is not due to the absence of antibodies against this predator. Predation in human serum was inhibited, though, by both the osmolality and serum albumin. The activity of B. bacteriovorus HD100 showed a sharp transition between 200 and 250 mOsm/kg, and was progressively reduced as the osmolality increased. Serum albumin also acted to inhibit predation by binding to and coating the predatory cells. This was confirmed via dot blot analyses and confocal microscopy. The results from both the osmolality and serum albumin tests were incorporated into a numerical model describing bacterial predation of pathogens. In conclusion, both of these factors inhibit predation and, as such, they limit its effectiveness against pathogenic prey located within sera

Genital Herpes Has Played a More Important Role than Any Other Sexually Transmitted Infection in Driving HIV Prevalence in Africa

Extensive evidence from observational studies suggests a role for genital herpes in the HIV epidemic. A number of herpes vaccines are under development and several trials of the efficacy of HSV-2 treatment with acyclovir in reducing HIV acquisition, transmission, and disease progression have just reported their results or will report their results in the next year. The potential impact of these interventions requires a quantitative assessment of the magnitude of the synergy between HIV and HSV-2 at the population level.A deterministic compartmental model of HIV and HSV-2 dynamics and interactions was constructed. The nature of the epidemiologic synergy was explored qualitatively and quantitatively and compared to other sexually transmitted infections (STIs). The results suggest a more substantial role for HSV-2 in fueling HIV spread in sub-Saharan Africa than other STIs. We estimate that in settings of high HSV-2 prevalence, such as Kisumu, Kenya, more than a quarter of incident HIV infections may have been attributed directly to HSV-2. HSV-2 has also contributed considerably to the onward transmission of HIV by increasing the pool of HIV positive persons in the population and may explain one-third of the differential HIV prevalence among the cities of the Four City study. Conversely, we estimate that HIV had only a small net impact on HSV-2 prevalence.HSV-2 role as a biological cofactor in HIV acquisition and transmission may have contributed substantially to HIV particularly by facilitating HIV spread among the low-risk population with stable long-term sexual partnerships. This finding suggests that prevention of HSV-2 infection through a prophylactic vaccine may be an effective intervention both in nascent epidemics with high HIV incidence in the high risk groups, and in established epidemics where a large portion of HIV transmission occurs in stable partnerships

True versus False Parasite Interactions: A Robust Method to Take Risk Factors into Account and Its Application to Feline Viruses

International audienceBACKGROUND: Multiple infections are common in natural host populations and interspecific parasite interactions are therefore likely within a host individual. As they may seriously impact the circulation of certain parasites and the emergence and management of infectious diseases, their study is essential. In the field, detecting parasite interactions is rendered difficult by the fact that a large number of co-infected individuals may also be observed when two parasites share common risk factors. To correct for these "false interactions", methods accounting for parasite risk factors must be used. METHODOLOGY/PRINCIPAL FINDINGS: In the present paper we propose such a method for presence-absence data (i.e., serology). Our method enables the calculation of the expected frequencies of single and double infected individuals under the independence hypothesis, before comparing them to the observed ones using the chi-square statistic. The method is termed "the corrected chi-square." Its robustness was compared to a pre-existing method based on logistic regression and the corrected chi-square proved to be much more robust for small sample sizes. Since the logistic regression approach is easier to implement, we propose as a rule of thumb to use the latter when the ratio between the sample size and the number of parameters is above ten. Applied to serological data for four viruses infecting cats, the approach revealed pairwise interactions between the Feline Herpesvirus, Parvovirus and Calicivirus, whereas the infection by FIV, the feline equivalent of HIV, did not modify the risk of infection by any of these viruses. CONCLUSIONS/SIGNIFICANCE: This work therefore points out possible interactions that can be further investigated in experimental conditions and, by providing a user-friendly R program and a tutorial example, offers new opportunities for animal and human epidemiologists to detect interactions of interest in the field, a crucial step in the challenge of multiple infections