Cofactor For HIV Transmission Research Articles

HSV-2 Infection as a Potential Cofactor for HIV Disease Progression and Selection of Drug Resistance Mutations in Adults under WHO-Recommended First-Line Antiretroviral Therapy: A Multicentric, Cross-Sectional Study in Cameroon, Central African Republic, Chad, and Gabon.

Although herpes simplex virus-2 (HSV-2) infection is a known cofactor for HIV transmission in Central Africa, its role in HIV disease progression is unclear. The aim of this study was to examine the potential link between HSV-2 infection and HIV disease progression, in addition to identifying the presence of genes conferring HIV antiretroviral resistance mutations. This was a cross-sectional study involving 302 HIV-infected adults in Central Africa with virological failure (viral load >1000 copies/mL) on first-line antiretroviral therapy from four different countries. The seroprevalence of HSV-2 was 32% (96/302). Amongst the HIV-infected individuals who were HSV-2 seropositive, the mean HIV viral load and CD4 count were 4.82 ± 0.83 log copies/mL and 243 ± 144 cells/microliter, respectively. Among the HIV-infected individuals who were HSV-2-seronegative, the mean HIV viral load and CD4 count were 3.48 ± 0.44 log copies/mL and 646 ± 212 cells/microliter, respectively (p < 0.001). There was a statistically significant relationship (p < 0.001) between HSV-2 seropositivity and the presence of resistance mutations to antiretrovirals (ARV), non-nucleoside reverse transcriptase inhibitors (NNRTI), and nucleoside reverse transcriptase inhibitors (NRTI) with odds ratios of 9.7, 10, and 11.9, respectively. There was no link between HSV-2 serostatus and protease inhibitor (PI) resistance mutations. There was a substantial accumulation of resistance mutations in HSV-2-seropositive compared to -seronegative patients. These findings support the link between HIV disease progression and HSV-2 infection. An association was observed between the presence of NNRTI and NRTI resistance mutations and HSV-2 seropositivity.

Rapid and sensitive detection of Chlamydia trachomatis sexually transmitted infections in resource-constrained settings in Thailand at the point-of-care.

Chlamydia trachomatis is the leading cause of sexually transmitted diseases (STDs) in females and males in both developed and developing countries, with more than 110 million cases annually. C. trachomatis resists antibiotic treatment and is a cofactor in HIV transmission and human cervical cancer [1]. Infection is often asymptomatic, causing the epidemiology to be underestimated. Therefore, we have developed a rapid, inexpensive, easy-to-interpret, sensitive and specific point-of-care (POC) C. trachomatis detection system, using loop-mediated isothermal amplification (LAMP) for target C. trachomatis DNA amplification, followed by gold nanoparticle probe (AuNP) for colorimetric C. trachomatis specific readout. The assay was evaluated using clinical samples and compared with polymerase chain reaction (PCR) of the same target gene, which is an outer membrane protein A (ompA) gene and a respected standard for C. trachomatis detection [1,2]. For nucleic acid amplification tests, recently LAMP has presented an attractive alternative to standard methods like PCR due to its low price, ease of use, rapid results, and lack of requirement for an expensive thermal cycler and specialized kits for DNA extraction and purification. A simple 5-minute boil for crude DNA lysis is sufficient for the LAMP reaction because the Bacillus stearothermophilus (Bst) DNA polymerase in LAMP has fewer inhibitor problems than Thermus aquaticus (Taq) DNA polymerase in PCR [3]. LAMP amplifies the target at a single temperature with high sensitivity (from 10 to 100 genome copies), and the product can be visualized as a white magnesium pyrophosphate precipitate. However, nebulous precipitate has the potential to cause misreading [3,4], so analysis by agarose gel-electrophoresis (GE), as with PCR, is standard. The positive LAMP reaction appears as multiple bands because several primers amplify amplicons of different sizes that are intercalated. Nevertheless, GE requires an electrophoresis apparatus, time, and often ethidium bromide exposure. In the current study, crude DNA lysis with combined LAMP-AuNP for POC C. trachomatis detection has been developed, and the specificity and limit of detection were validated by several positive and negative C. trachomatis genomes, as well as the possibility for POC diagnostic based on a statistical number of clinical endocervical swab sample tests (see Box 1). Box 1: Advantages and disadvantages of C. trachomatis LAMP-AuNP. Advantages Sensitive to as low as 11.25 copies of target DNA Total assay time is <1 hour Evaluation in independent replicates in 130 clinical samples showed 96% sensitivity and 99% to 100% specificity Disadvantages Cannot diagnose the severity of disease Reaction reagents are in liquid Color change observation may be difficult for low copy numbers of Chlamydia trachomatis Materials and methods Study design and clinical sample collections The criteria for symptomatic C. trachomatis was obtained from the description by the Centers for Disease Control and Prevention (CDC), such as abnormal cervical or vaginal discharge, elevated number of white blood cells in vaginal secretion, and co-infection with Neosseria gonorrhoeae [1]. Endocervical swab samples were randomly selected from a prospective study cohort of STD prevalence in symptomatic and healthy (which may include nonsymptomatic patients) Thai women aged 15 to 54 years in Bangkok and nearby areas. The samples were collected by clinicians during 2011 and 2012 from qualified volunteers attending the Buddhachinaraj Phitsanulok Hospital, and in 2013 and 2014 from Bangrak and Chonburi offices of Disease Prevention and Control [2]. The sample size of 130 (96 symptomatic and 34 healthy) was computed based on a standard statistical formula (http://www.calculator.net/sample-size-calculator.html), given the prevalence rates of C. trachomatis as 22% for symptomatic STDs and 3% for healthy people [2], with a margin of error of 0.05, and a 90% confidence interval. The samples were stored in 3 mL standard C. trachomatis collection medium M4RT (Thermo Fisher Scientific, Kansas, USA) at −80°C.

Time to manage Mycoplasma genitalium as an STI

Mycoplasma genitalium is a sexually transmitted infection that causes significant morbidity in men and women and is a co-factor in HIV transmission. However, commercial diagnostic tests are not generally available for M. genitalium and sub-optimal treatment is often given. We review the literature on the burden of infection, how it may present in clinical practice and the effectiveness of current treatment regimens. In-vivo and in-vitro data strongly suggest that M. genitalium is an important cause of urethritis, cervicitis, pelvic inflammatory disease and potentially asymptomatic proctitis. Studies now consistently demonstrate suboptimal eradication rates with the current treatment regimens recommended first line for the treatment of nongonococcal urethritis. Concurrently, there has been a rapid emergence of antibiotic resistance in M. genitalium, with macrolide resistance now appearing to be endemic in some centres, and quinolone resistance is beginning to emerge. In the absence of specific M. genitalium diagnostic and antimicrobial resistance testing, azithromycin 1 g should not be used for the management of patients with symptomatic disease potentially caused by M. genitalium. This review offers an alternative evidence-based approach to managing such patients that should, theoretically, reduce the risk of the development of antimicrobial resistance.

Sexual violence and HIV transmission: summary proceedings of a scientific research planning meeting.

This summarizes proceedings of a Scientific Research Planning Meeting on Sexual Violence and HIV transmission, convened by the Social Science Research Council on 19–20 March 2012 at the Greentree Foundation in New York. The Meeting brought together an interdisciplinary group of basic, clinical, epidemiological and social science researchers and policy makers with the aim of: (1) examining what is known about the physiology of sexual violence and its role in HIV transmission, acquisition and pathogenesis; (2) specifying factors that distinguish risks throughout the maturation of the female genital tract, the reproductive cycle and among post-menopausal women; and (3) developing a research agenda to explore unanswered questions. The Meeting resulted in a consensus Research Agenda and White Paper that identify priorities for HIV research, policy and practice as it pertains to the role of sexual violence and genital injury in HIV transmission, acquisition and pathogenesis, particularly among women and girls.

Anti-Trichomonas vaginalis activity of saponins from Quillaja, Passiflora, and Ilex species

Trichomonas vaginalis is a flagellated protozoan that causes trichomonosis, the most prevalent non-viral STD worldwide. The pathogen has been associated with serious health consequences including predisposition to cervical cancer and adverse pregnancy outcomes and infertility. It also acts as a co-factor in HIV transmission and acquisition. The 5-nitroimidazole drugs are used in the treatment, however, treatment noncompliance is observed, and a growing number of T. vaginalis isolates resistant to the drugs have been related. Saponins are natural products possessing many biological activities such as antiprotozoan activity. The aim of this study was to evaluate the anti-T. vaginalis activity of saponins from Quillaja, Passiflora, and Ilex species. Saponins from Passiflora alata and Quillaja saponaria presented the best anti-T. vaginalis activity (MIC = 0.025%). In addition, all samples induced erythrocyte lysis and LDH release. As far as we know, this is the first report demonstrating the potential anti-T. vaginalis activity of these saponins.

Importance of sexually transmitted infections in funding for HIV within proposals to the Global Fund

Yearly, an estimated 448 million treatable sexually transmitted infections (STIs)1 occur worldwide. Over 80% of all new HIV infections are acquired through sexual transmission.2 The enormous burden of morbidity and...

Could implementation of Australia's National Gay Men's Syphilis Action Plan have an indirect effect on the HIV epidemic?

The number of incident infections of syphilis and HIV have increased over the past decade across Australia, particularly among gay men. In other industrialised settings, syphilis epidemics have also resurged coincidentally with increases in HIV diagnoses. Sexually transmissible infections (STI) are a biologically plausible cofactor for increasing HIV transmission. We pose the question: could strategies purely targeting syphilis also have an indirect impact on HIV incidence? We developed an agent-based computer model that simulates the transmission and disease progression of HIV and syphilis among a population of sexually active gay men, calibrated to reflect the epidemics in Victoria, Australia. The model was informed by detailed behavioural data from a variety of sources and was used to investigate the potential epidemiological impact of different public health interventions. Assuming that syphilis could act as a biological cofactor for HIV transmission, from no effect to increasing risk by five-fold, our model indicates that if Australia's syphilis action plan is effectively implemented then the number of HIV infections could decrease by up to 48% over the next decade in the absence of any specific HIV interventions. It is plausible that effective implementation of interventions targeting syphilis epidemics can have an indirect effect of mitigating the spread of HIV. The possible effects of STI should be considered in the design, implementation and evaluation of public health strategies and programs.

The prevalence of sexually transmitted infections in Papua New Guinea: a systematic review and meta-analysis.

BackgroundThe potential for an expanded HIV epidemic in Papua New Guinea (PNG) demands an effective, evidence-based and locally-appropriate national response. As sexually transmitted infections (STIs) may be important co-factors in HIV transmission nationally, it is timely to conduct a systematic review of STI prevalences to inform national policy on sexual health and HIV/STI prevention.Methodology/Principal FindingsWe undertook a systematic review and meta-analysis of HIV and STI prevalences in PNG, reported in peer-reviewed and non-peer-reviewed publications for the period 1950–2010. Prevalence estimates were stratified by study site (community or clinic-based), geographic area and socio-demographic characteristics. The search strategy identified 105 reports, of which 25 studies (10 community-based; 10 clinic-based; and 5 among self-identified female sex workers) reported STI prevalences and were included in the systematic review. High prevalences of chlamydia, gonorrhoea, syphilis and trichomonas were reported in all settings, particularly among female sex workers, where pooled estimates of 26.1%, 33.6%, 33.1% and 39.3% respectively were observed. Pooled HIV prevalence in community-based studies was 1.8% (95% CI:1.2–2.4) in men; 2.6% (95% CI:1.7–3.5) in women; and 11.8% (95% CI:5.8–17.7) among female sex workers.Conclusions/SignificanceThe epidemiology of STIs and HIV in PNG shows considerable heterogeneity by geographical setting and sexual risk group. Prevalences from community-based studies in PNG were higher than in many other countries in the Asia-Pacific. A renewed focus on national STI/HIV surveillance priorities and systems for routine and periodic data collection will be essential to building effective culturally-relevant behavioural and biomedical STI/HIV prevention programs in PNG.

Synergistic effects of STI Control and HIV prevention Presented at the International Congress of Sexually Transmitted Infections (ISSTDR/IUSTI) 2001, Berlin

Provision of early and effective treatment of STD impacts on HIV transmission by shortening the duration of a biological cofactor for HIV transmission, which can lead to reduced infectiousness in an HIV positive person or reduced susceptibility in an HIV negative person. In addition, offering good quality STD services, integrated into the existing healthcare centres or set up as special programmes for hard-to-reach populations, such as young people or sex workers, provides unique opportunities to offer and reinforce prevention messages. This care-prevention synergy has been thoroughly documented in projects involving sex workers in the Democratic Republic (RD) of Congo and Côte d'Ivoire, where integrated packages of services have facilitated getting in touch with a large number of women who never sought STD care before, and reinforced the preventive messages, leading to a dramatic decline in new HIV infections over the years. Currently, multiple integrated reproductive service packages, including STD care for youth groups, are being put in place and their synergistic impact on HIV prevention is being investigated.

Syndrome packets and health worker training improve sexually transmitted disease case management in rural South Africa: randomized controlled trial

Sexually transmitted diseases (STD) are important co-factors in HIV transmission. We studied the impact of health worker training and STD syndrome packets (containing recommended drugs, condoms, partner notification cards and information leaflets) on the quality of STD case management in primary care clinics in rural South Africa. A randomized controlled trial of five matched pairs of clinics compared the intervention with routine syndromic management. Outcomes were measured by simulated patients using standardized scripts, and included the proportion given recommended drugs; correctly case managed (given recommended drugs plus condoms and partner cards); adequately counselled; reporting good staff attitude; and consulted in privacy. At baseline, the quality of STD case management was similarly poor in both groups. Only 36 and 46% of simulated patients visiting intervention and control clinics, respectively, were given recommended drugs. After the intervention, intervention clinics provided better case management than controls: 88 versus 50% (P < 0.01) received recommended drugs; 83 versus 12% (P < 0.005) were correctly case managed; 68 versus 46% (P = 0.06) were adequately counselled; 84 versus 58% experienced good staff attitude (P = 0.07); and 92 versus 86% (P = 0.4) were consulted privately. A syndrome packet cost US$1.50; the incremental cost was US$6.80. The total intervention cost equalled 0.3% of annual district health expenditure. A simple and affordable health service intervention achieved substantial improvements in STD case management. Although this is a critical component of STD control and can reduce HIV transmission, community-level interventions to influence health-seeking behaviour are also needed.

Chancroid: from clinical practice to basic science.

Chancroid is a sexually transmitted disease caused by the bacterium Haemophilus ducreyi. It usually presents as a genital ulcer and may be associated with regional lymphadenopathy and bubo formation. H. ducreyi infection is predominantly seen in tropical resource-poor regions of the world where it is frequently the most common etiological cause of genital ulceration. Genital ulcer disease has been shown to be an extremely important co-factor in HIV transmission. With the advent of the AIDS epidemic, there has been increased research effort to elucidate those factors involved in the pathogenesis of chancroid. Several putative virulence factors have now been identified and isogenic H. ducreyi mutants constructed by mutagenesis of their encoding genes. This approach has facilitated investigations into the role each of these putative virulence factors may play in H. ducreyi pathogenesis through the use of in vitro and in vivo model systems. One major goal of current chancroid research is to identify antigens which are immunogenic and could form the basis of a vaccine against H. ducreyi infection. Such a vaccine, if shown to be effective in decreasing the prevalence of chancroid, could have the added benefit of slowing down the HIV incidence rates in those populations where chancroid is a major co-factor for HIV transmission.

HIV/AIDS in Bangladesh: an assessment of biomedical risk factors for transmission.

Behavioural risk factors for HIV/AIDS in Bangladesh were reviewed in a preceding article in this journal. Omitted from that review was a discussion of potential biomedical risk factors including: (i) an unregulated blood supply system in which blood used in transfusions is not screened for HIV and is donated primarily by professional donors: (ii) unsterile injections in non-formal and formal health-care settings; and (iii) a high prevalence in high-risk groups of other sexually transmitted diseases (STDs) which may function as co-factors for HIV transmission, particularly if chronically untreated. Studies elsewhere in the world suggest that the unregulated blood supply system, in particular, poses a serious danger in terms of the spread of the HIV epidemic. While certain socio-cultural factors may be contributing to low levels of HIV in Bangladesh, the prevalence of biomedical and behavioural risk factors suggest the importance of implementing targeted cost-effective interventions now.

Sperm as infection-potentiating cofactors in HIV transmission

In this paper I will discuss the possible role of sperm as cofactors in the genital-mucosal transmission of HIV. The ideas involved arose from my laboratory’s discovery that sperm bind to HLA-DR molecules expressed on somatic cells, and from our subsequent findings that lymphocytes are activated by these interactions. Sperm binding to HLA-DR mimics one of the two ligand binding characteristics of superantigens, which also bind to T-cell receptors in a V- β-specific fashion. This property of sperm may be significant in HIV transmission because: (a) HLA-DR plays a central role in immune recognition and response; and (b) cell interactions involving HLA-DR are involved in HIV infection and disease development. After sexual contact, sperm elicit a transient leukocytic infiltration of the mammalian cervix (Thompson, L.A., Barratt, C.L., Bolton, A.E., Cooke, I.D., 1992. The leukocytic reaction of the human cervix. Am. J. Reprod. Immunol. 28, 85; Pandya, I.J., Cohen, J., 1985. The leukocytic reaction of the human uterine cervix to sperm. Fertil. Steril. 43, 417), and human cervical cells are bound and penetrated by sperm at this time (Sievers-Altermann, R., Engelbrecht, D.V., 1990. Entry of spermatozoa into the cervical mucosa and transmission of the AIDS virus. S. Afr. Med. J. 77, 319). At present, little is known about these in vivo events, but sperm-somatic cell interactions in vitro are also followed by sperm entry into the target cell cytoplasm and target cell activation. When the target cells are leukocytes, sperm interactions increase their susceptibility to HIV infection. If similar interactions occur in the cervicovaginal environment after sexual contact, they are likely to enhance the genital-mucosal transfer of HIV from semen.

Letters to the Editor

Unrecognized genital ulcer disease may be a significant co-factor in HIV transmission in South Africa. The prevalence of genital ulcers was investigated in three groups of women in KwaZulu/Natal South Africa: 327 antenatal clinic patients and 189 family planning clinic clients in rural Hlabisa and 145 sex workers operating at truck stops on the main route from Durban to Johannesburg. 21 sex workers (14%) 6 pregnant women (2%) and 5 family planning clients (3%) had at least 1 genital ulcer; all were vulval. None of the sex workers or pregnant women and only 2 family planning clients were aware they had a genital ulcer. Most of these women reported abnormal urogenital symptoms and had other sexually transmitted infections that may have masked ulcer-related discomfort. 75% of these women were HIV-infected. This too may affect the symptomatology and natural history of genital ulcer disease.

Sexually transmitted infection in women

Sexually transmitted infections are major causes of morbidity in young women throughout the world, and are now recognized to be important co-factors in HIV transmission. This paper gives an overview of the prevention and care of sexually transmitted diseases including HIV, an update of their epidemiology, and recent advances in treatment. HIV infection in women is becoming more common, with more babies being born to infected women. The risk of vertical transmission from mother to baby can be reduced significantly by interventions such as avoidance of breastfeeding and the use of the antiviral drug zidovudine. Interventions cannot be offered unless pregnant women with HIV are identified, which highlights the need to establish voluntary named antenatal screening programmes.

Syphilis and HIV infection among displaced pregnant women in rural Mozambique.

A cross-sectional study was conducted among displaced pregnant women in Mozambique to determine the prevalence and correlates of HIV infection and syphilis. Between September 1992 and February 1993, 1728 consecutive antenatal attendees of 14 rural clinics in Zambézia were interviewed, examined, and tested for HIV and syphilis antibodies. The seroprevalence of syphilis and HIV were 12.2% and 2.9%, respectively. Reported sexual abuse was frequent (8.4%) but sex for money was uncommon. A positive MHA-TP result was significantly associated with unmarried status, history of past STD, HIV infection, and current genital ulcers, vaginal discharge, or genital warts. Significant correlates of HIV seropositivity included anal intercourse, history of past STD, and syphilis. In summary, displaced pregnant women had a high prevalence of syphilis but a relatively low HIV seroprevalence suggesting recent introduction of HIV infection in this area or slow spread of the epidemic. A syphilis screening and treatment programme is warranted to prevent perinatal transmission and to reduce the incidence of chancres as a cofactor for HIV transmission.