Proportion Of HIV-infected Persons Research Articles

A study for precision diagnosing and treatment strategies in difficult-to-treat AIDS cases and HIV-infected patients with highly fatal or highly disabling opportunistic infections: Study protocol for the optimal early intervention for cryptococcal antigenemia in HIV-infected patients.

Background:Asymptomatic cryptococcal antigenemia is a state of cryptococcal infection commonly seen in immunocompromised HIV-infected persons. Without early intervention, a proportion of HIV-infected persons with cryptococcal antigenemia may go on to develop cryptococcosis, especially cryptococcal meningitis, which is associated with high mortality. The benefits of antifungal intervention and optimal therapeutic intervention regimens for HIV-infected persons with cryptococcal antigenemia remain controversial. We therefore designed the present study in order to investigate the necessity of, and the optimal regimens for antifungal intervention in the clinical management of cryptococcal antigenemia in HIV-infected populations.Methods/Design:This study will be an open-labeled, multi-center, prospective, randomized controlled trial, and 450 eligible participants will be randomized into a control arm and 2 intervention arms at a 1:1:1 ratio, with 150 subjects in each arm. Participants in the control arm will not receive antifungal treatment during the study period. Participants in intervention arm 1 will receive oral fluconazole 800 mg/day for 2 weeks, followed by 400 mg/day for 8 weeks and 200 mg/day for 42 weeks, and participants in intervention arm 2 will receive oral fluconazole 400 mg/day for 52 weeks. The primary outcome is the incidence of CM among the 3 groups during the study period. The secondary outcomes include the differences in all-cause mortality, proportion of patients reverting to blood CrAg negativity, change of CrAg titers, and adverse events among the 3 groups during the follow-up period.Discussion:We envisage that the results of this study will reveal the necessity of, and the optimal therapeutic regimens for, antifungal intervention in clinical management of HIV-infected patients with cryptococcal antigenemia.Trial registration:The study was registered as one of the 12 clinical trials under a general project at the Chinese Clinical Trial Registry on February 1, 2019, and the registration number of the general project is ChiCTR1900021195.

Drug resistance from preferred antiretroviral regimens for HIV infection in South Africa: A modeling study.

BackgroundTenofovir-containing regimens comprise the preferred first-line antiretroviral therapy (ART) in many countries including South Africa, where utilization of second-line regimens is limited. Considerable HIV drug resistance has occurred among persons failing tenofovir-containing first-line ART. We evaluated drug resistance at the population level using mathematical modeling.SettingHeterosexual HIV epidemic in KwaZulu-Natal, South Africa.MethodsWe constructed a stochastic individual-based model and simulated scenarios of ART implementation, either CD4-based (threshold < 500 cells/mL) or Fast-track (81% coverage by 2020), with consideration of major drug-associated mutations (M184V, K65R and non-nucleoside reverse transcriptase inhibitor (NNRTI)). Using base case and uncertainty analyses, we assessed (majority) drug resistance levels.ResultsBy 2030, the median total resistance (proportion of HIV-infected persons with drug resistance) is predicted to reach 31.4% (interquartile range (IQR): 16.5%-50.2%) with CD4-based ART, decreasing to 14.5% (IQR: 7.7%-25.8%) with Fast-track implementation. In both scenarios, we find comparably high prevalence (~80%) of acquired NNRTI-associated, M184V and K65R mutations. Over 48% of individuals with acquired resistance harbor dual, 44% triple and 7% just single drug mutations. Drug-resistant HIV is predicted to comprise 40% (IQR: 27%-50%) of incident infections, while 70% of prevalent transmitted resistance is NNRTI-associated. At 2018, the projected total resistance is 15% (IQR: 7.5%-25%), with 18% (IQR: 13%-24%) of incident infections from transmitted drug-resistant HIV.ConclusionsWHO-recommended preferred first-line ART could lead to substantial drug resistance. Effective surveillance of HIV drug resistance and utilization of second-line as well as alternative first-line regimens is crucial.

Drug Resistance After Failure of WHO Recommended First-Line Antiretroviral Regimen for Adult HIV-1 Infection in South Africa: A Modeling Analysis

BackgroundAntiretroviral therapy (ART) is critical for ending the HIV epidemic. Tenofovir-containing ART is the first-line regimen in many countries including South Africa, with limited access to second-line ART. High levels of drug resistance have been reported among patients after virologic failure on tenofovir-containing first-line regimens (TenoRes Study, Lancet Infect Dis 2016). We assessed drug resistance at the population level using mathematical modeling.MethodsWe developed a stochastic individual-based model of the heterosexual HIV epidemic in KwaZulu-Natal South Africa, and compared drug resistance from scenarios of tenofovir-containing ART scale-up, either CD4-based (threshold < 500 cells/mL) or Fast-track (80% coverage by 2020). The model represents details of HIV transmission and disease progression, demography, sexual behavior, condom use, circumcision, treatment interventions and drug resistance dynamics including key mutations (M184V, K65R and non-nucleoside reverse transcriptase inhibitor (NNRTI)). Using an initial population of 2.5 million, we performed 100 simulations from 1978 to 2030. We examined the prevalence of (majority) transmitted and acquired resistance by 2030.ResultsThe total resistance (proportion of HIV-infected persons with drug resistance) reached 34% from CD4-based ART by 2030, with 30% relative contribution from transmitted resistance and 70% from acquired resistance. In contrast, Fast-track ART reduced the total resistance to 22%; though, there was an increased relative contribution from transmitted resistance (~ 50%). In both scenarios, NNRTI mutations were the most prevalent, followed by M184V and K65R mutations. About 48% of persons with acquired drug- resistance harbored dual drug mutations, 44.7% had triple mutations and 7.3% just single mutations, from CD4-based ART. The respective estimates from Fast-track ART were similar; 49% for dual, 44.1% for triple and 6.9% for single mutations. In both scenarios, NNRTI mutations comprised about 80% of prevalent transmitted resistance.ConclusionCurrent WHO-recommended first-line ART could lead to substantial drug resistance. Effective surveillance for resistance transmission and access to second-line regimens would be crucial.Disclosures All authors: No reported disclosures.

Multiform spectrum of pulmonary disease in lethal HIV infection cases in Latvia (2012–2016)

In 2016, the proportion of HIV-infected persons in the Baltic countries was as follows: Latvia 18.5, Estonia 17.4, Lithuania 7.4 per 100,000 of population. The aim of our study was to evaluate the spectrum and morphology of combined lung pathologies in fatal HIV/AIDS cases in Latvia from 2010 to 2016. We did a retrospective review of the HIV/AIDS patients’ medical autopsy case files and histological slides at the Pathology Centre of Riga Eastern Clinical University Hospital. All statistical data were processed in IBM SPSS Statistics 23. We analysed 455 cases – 311 (69%) men, 134 (31%) women. The mean age of the analysed patients was 40 years (±9 SD, range 22–68). The conditions leading to death were opportunistic infections (OI) – 28%, tuberculosis (TB) – 23%, wasting syndrome complicated by nonspecific pneumonia and sepsis or HIV/AIDS unrelated conditions – 27%, malignancies – 11% (B large cell lymphoma, primary and secondary cancers of the lung, Kaposi sarcoma), and end stage liver disease – 11%. Lungs were affected in 380 cases (83.5%). We identified 112 cases of tuberculosis (TB). In 21%, it was isolated pulmonary TB, in 79% – disseminated TB. Additionally, OI were proved in 26% of these patients. The prevalence of OI was higher in patients who died from isolated pulmonary TB. We also identified 10 cases of disseminated atypical mycobacteriosis. Opportunistic infections were diagnosed in 126 persons – 77% (n=97) of them had one, but 23% (n=29) had two or more OIs. The most common isolated OI with lung involvement was Pneumocystis jiroveci (PC) pneumonia (n=71, 15.6%); 10% had cryptococcosis, 1% – pulmonary aspergillosis and Candida pneumonia each. 40 patients (9%) had disseminated cytomegalovirus (CMV). Among the various combinations of oppor tunistic infections, the most common was PC+CMV. 81% of HIV patients were unemployed and prisoners with interrupted treatment. We concluded that our study revealed that combined opportunistic infections and TB were the most frequently observed pulmonary infections, followed by primary and secondary lung malignancies and bacterial pneumonia in HIV/AIDS unrelated cases of multiorgan disease. Diagnostic difficulties occurred mainly in disseminated diseases due to nonspecific clinical presentation, similar appearance on imaging studies and limited bacterial diagnostic possibilities after death.

A Flow-Based Model of the HIV Care Continuum in the United States.

Understanding the flow of patients through the continuum of HIV care is critical to determine how best to intervene so that the proportion of HIV-infected persons who are on antiretroviral treatment and virally suppressed is as large as possible. Using immunological and virological data from the Centers for Disease Control and Prevention and the North American AIDS Cohort Collaboration on Research and Design from 2009 to 2012, we estimated the distribution of time spent in and dropout probability from each stage in the continuum of HIV care. We used these estimates to develop a queueing model for the expected number of patients found in each stage of the cascade. HIV-infected individuals spend an average of about 3.1 months after HIV diagnosis before being linked to care, or dropping out of that stage of the continuum with a probability of 8%. Those who link to care wait an additional 3.7 months on average before getting their second set of laboratory results (indicating engagement in care) or dropping out of care with probability of almost 6%. Those engaged in care spent an average of almost 1 year before achieving viral suppression on antiretroviral therapy or dropping out with average probability 13%. For patients who achieved viral suppression, the average time suppressed on antiretroviral therapy was an average of 4.5 years. Interventions should be targeted to more rapidly identifying newly infected individuals, and increasing the fraction of those engaged in care that achieves viral suppression.

Late HIV diagnosis in Europe: A call for increased testing and awareness among general practitioners

Major advancements in the treatment of HIV infection mean near normal life expectancy of persons diagnosed at an early stage of infection. Nevertheless, a significant proportion of HIV infected persons remain undiagnosed and are diagnosed at a late stage of infection, putting them at higher risk for preventable HIV-related morbidity and mortality and risking onward transmission to others. In Europe, half of people diagnosed with HIV in 2010 were diagnosed late with a CD4<350 cells/ul, at a point after which treatment should have begun. The causes of late diagnosis are manifold, and comprise barriers to testing at the patient, healthcare provider, and institutional level. Strategies to address barriers to HIV testing are essential to ensure prompt diagnosis. Routine universal HIV testing in general practice consisting of informed consent and a pre-test discussion is feasible and acceptable and should be considered in high prevalence areas to normalize HIV testing, reduce stigma, and reduce the number of infected individuals who are diagnosed late.

Prevalence and Incidence of Syphilis Among South American Transgender Sex Workers in Northern Italy

To the Editor: Sex workers (SWs) constitute a core group that are known to be highly vulnerable to sexually transmitted infections (STIs) and HIV.1 The number of migrant men and women engaging in prostitution has increased in the past few years in Italy, especially in the northern regions.2 Migrant SWs are unregistered because prostitution is a nonregulated activity in Italy. They are often socially stigmatized and economically disadvantaged, have limited access to health services, and are difficult to reach by information campaigns. Transgender SWs have been reported as a group with a particularly high prevalence and incidence of HIV,3 but limited data are available on other STIs in this population. We describe here the prevalence and incidence of syphilis and HIV among South American male to female (MTF) transgender persons in Brescia, Northern Italy. These persons are phenotypically women and their gender self-identification is female, but none has had surgery. Their clients are male in gender, are not homosexuals, and they are definitely aware they are engaging in sex with a MTF transgender SW. We retrospectively analyzed the clinical charts at the sexually transmitted disease clinic in Brescia. The clinic is the only public health structure providing free and anonymous counseling and testing for HIV and STIs in the District of Brescia and is therefore the reference centre for undocumented SWs. We performed chart abstraction of all persons who 1) were male to female transgender, 2) had identified themselves as SWs, 3) had at least one syphilis serology result, and 4) were foreign-born persons from South America. A prevalent case of active syphilis was defined as a person with a reactive Treponema pallidum hemagglutination (TPHA) and rapid plasma reagin (RPR) test. An incident syphilis case was defined as a person with a nonreactive TPHA serology at baseline with a reactive TPHA and RPR serology at follow up. From April 2002 to January 2004, 86 eligible cases were identified. Their mean age was 27.8 years, 91% were from Brazil, and 9% were from Colombia. Regular condom use with clients was reported by 79%. Twelve prevalent cases of syphilis were identified (14.0%). They were all classified as latent syphilis cases. None presented with concomitant gonococcal or chlamydial infection. In addition, 15 clients had a positive TPHA but a negative RPR. The HIV test was accepted by 85 subjects; 23 of them were positive (27.1%). The proportion of HIV-infected persons was 42.3% (11 of 26) among those with a positive TPHA test, and 20.3% (12 of 59) among those with a negative TPHA test (odds ratio = 2.87, confidence interval = 0.94–8.85, P <0.04). Of the 59 subjects who were initially TPHA-negative, 19 were reevaluated 6 months or more after the first evaluation and had repeated tests for HIV and syphilis; syphilis incidence was measured in this retrospective cohort. Five incident cases of syphilis were identified during a mean follow-up period of 24.1 months for an incidence rate of 13.1 per 100 person per year. No HIV seroconversion was observed. Our date suggest high incidence of syphilis among MTF transgender prostitutes in Italy and add to the evidence of a reemergent syphilis epidemic among men who exchange money for sex in the United States,4 the United Kingdom,5 and Italy.6 Increasing rates of syphilis raise concern about the potential increase in HIV incidence; the former is an early indicator of resurgence of risky sexual behaviors and HIV transmission and acquisition.7 In addition, because the clients of MTF transgender SWs are not homosexual men, a potential bridge to the heterosexual population can be established. This study has several limitations; first, the retrospective design; second, the nonrandom sampling of transgender subjects both at baseline and at follow up; and third, the small number of subjects both at baseline and follow up. However, collection of exhaustive epidemiologic data from transgender SWs is difficult because of the clandestine status and mobility. Despite these limitations, our data identify foreign-born transgender SWs and their clients as a group at very high risk for syphilis and potentially HIV. Control of HIV and STIs should include the provision of accessible and appropriate health services for foreign-born MTF transgender persons by the provision of testing, care, targeted education, and social support. Beyond this, efforts are warranted to disrupt the association between increased risk for STIs and stigmatization/marginalization of MTF transgender persons; such association is perpetuated by the difficulties in maintaining stable relationships, obtaining stable income, and coping with financial requirements for hormone therapy and surgical modifications.8

Disclosure of HIV status.

A significant proportion of HIV-infected persons choose not to disclose their status to sexual partners. Healthcare providers may play a role in motivating patients to disclose despite powerful forces working in favor of secrecy.

Computer-based interview for screening blood donors for risk of HIV transmission

Concern about the safety of the nation's blood supply continues to grow because of the expanding number of HIV-infected persons in the potential donor pool. Furthermore, the proportion of HIV-infected persons who engage in high-risk activities but who test seronegative may be higher than previously recognized. Despite improvements in HIV testing, it is doubtful that such testing alone will ever be adequate to eliminate transfusion-associated AIDS. Blood donation by recently infected persons must be reduced through improved donor screening, including direct questioning of donors about high risk behaviors. We have developed a computer-based interview that queries blood donors about factors that increase the risk of HIV transmission via blood donation. The interview was administered to 64 donors during a scheduled rest period after completing their blood donation. The interview required about nine minutes to complete. Results were analyzed to determine the donor reactions to the interview. Subjects enjoyed taking the interview, thought it was a good method for screening donors, and trusted the confidentiality of the interview. Donors believed they would be more honest with the computer interview than with a human interviewer. If automated blood donor screening helps to discourage donation by high-risk persons the rate of transfusion-associated AIDS will be reduced.

Human immunodeficiency virus infection and the acquired immune deficiency syndrome: A review

We are currently witnessing a global epidemic of a group of diseases which are known as AIDS and which have in common an underlying profound impairment of the host immune system. The causative agent,human immunodeficiency virus (HIV), has been identified and testing for antibodies to this virus has demonstrated its spread into many populations around the world. HIV is now known to give rise to a wide clinical spectrum including asymptomatic infection, progressive central nervous system infection, and the fatal immune deficiency termed AIDS. The proportion of HIV-infected persons who will eventually develop AIDS cannot be known with precision at this time although it is likely to be at least 40% and could be as high as 100%. AIDS and HIV have been reported in over half of the countries in the world including the USSR and China. The global distribution follows 3 epidemiologic patterns: that of the developed countries where the virus has primarily affected homosexual/bisexual men and intravenous drug users; that of Central Africa and parts of the Caribbean where it is essentially a heterosexually transmitted disease; and that of Asia and most of Central and South America where the disease is still rare. Although HIV has been recovered from peripheral blood, semen, saliva, tears, alveolar fluid, cerebrospinal fluid, brain tissue, and cervical and vaginal secretions, there is much data to indicate that its modes of spread are limited to sexual, parenteral (i.e. contaminated needles), iatrogenic (i.e. blood and blood products, transplantation, etc.), and perinatal (i.e. mother to offspring). There is now substantial evidence to indicate that casual contact, that is the type of non-sexual personal contact that might occur in the household, school setting, or workplace, does not give rise to HIV transmission. Similarly, transmission of HIV by insect vectors, e.g. mosquitoes, has also been effectively ruled out.

Human Immunodeficiency Virus Infection and the Acquired Immune Deficiency Syndrome: A Review

We are currently witnessing a global epidemic of a group of diseases which are known as AIDS and which have in common an underlying profound impairment of the host immune system. The causative agent, human immunodeficiency virus (HIV), has been identified and testing for antibodies to this virus has demonstrated its spread into many populations around the world. HIV is now known to give rise to a wide clinical spectrum including asymptomatic infection, progressive central nervous system infection, and the fatal immune deficiency termed AIDS. The proportion of HIV-infected persons who will eventually develop AIDS cannot be known with precision at this time although it is likely to be at least 40% and could be as high as 100%. AIDS and HIV have been reported in over half of the countries in the world including the USSR and China. The global distribution follows 3 epidemiologic patterns: that of the developed countries where the virus has primarily affected homosexual/bisexual men and intravenous drug users; that of Central Africa and parts of the Caribbean where it is essentially a heterosexually transmitted disease; and that of Asia and most of Central and South America where the disease is still rare. Although HIV has been recovered from peripheral blood, semen, saliva, tears, alveolar fluid, cerebrospinal fluid, brain tissue, and cervical and vaginal secretions, there is much data to indicate that its modes of spread are limited to sexual, parenteral (i.e. contaminated needles), iatrogenic (i.e. blood and blood products, transplantation, etc.), and perinatal (i.e. mother to offspring). There is now substantial evidence to indicate that casual contact, that is the type of non-sexual personal contact that might occur in the household, school setting, or workplace, does not give rise to HIV transmission. Similarly, transmission of HIV by insect vectors, e.g, mosquitoes, has also been effectively ruled out.