HIV This Week

Female genital tract secretions and semen impact the development of microbicides for the prevention of HIV and other sexually transmitted infections

Herold BC, Mesquita PM, Madan RP, Keller MJ. Am J Reprod Immunol. 2011; 65:325-333

Pharmacologic strategies for the prevention of HIV include vaccines, post-exposure prophylaxis with antiretroviral therapy, and topical microbicides. Vaginal microbicides have the potential to augment innate defenses in the genital tract but may also disrupt endogenous protection and increase HIV acquisition risk, as observed in clinical trials of nonoxynol-9. The initially disappointing results of microbicide clinical trials stimulated the development of more sensitive and comprehensive pre-clinical safety studies, which include dual-chamber culture systems to model the epithelial barrier and post-coital studies to evaluate the effects of semen and sexual intercourse on microbicide efficacy. This review discusses the key factors that contribute to a healthy female genital tract environment, the impact of semen on mucosal defense, and how our understanding of these mediators informs the development of effective vaginal microbicides.

Abstract

Editors’ note: This article provides strong justification for conducting pharmacokinetic and pharmacodynamic studies for microbicide candidates using post-coital samples rather than ordinary cervicovaginal secretions. The female genital tract has several natural host defences that semen counteracts. It neutralises the protective acidic pH of vaginal fluid, stimulates inflammatory cytokines, and causes white cells and Langerhans cells to come into the path of HIV. More directly, semen contains prostatic acid phosphatise which forms fibrils that capture HIV and help their attachment to target cells. Semen may also interfere with defensins, SLPI (secretory leukocyte protease inhibitor), and other antimicrobial proteins found in cervicovaginal secretions. Clearly, when we are trying to measure the effects of a microbicide candidate on the multilayered squamous epithelial barrier of the vagina we have to include semen. Predictive safety assays such as those described in this article are helping us understand why microbicide candidates such as non-oxynol 9 and cellulose sulfate increased risk of HIV acquisition. We need to better understand mucosal immunity and the role of semen in order to find ways to increase women’s natural defenses. In the meantime, reading this article brings the reader right back to square one—if there is any possibility of HIV or genital herpes, use a condom if you are not trying to get pregnant!

Estimate of the residual risk of transfusion-transmitted human immunodeficiency virus infection in sub-Saharan Africa: a multinational collaborative study

Lefrère JJ, Dahourouh H, Dokekias AE, Kouao MD, Diarra A, Diop S, Tapko JB, Murphy EL, Laperche S, Pillonel J. Transfusion. 2010 Sep 28. doi: 10.1111/j.1537-2995.2010.02886.x. [Epub ahead of print]

Sub-Saharan Africa remains the epicenter of the human immunodeficiency virus (HIV) pandemic. However, there is a lack of multicentre data on the risk of transfusion-transmitted HIV from blood centres in sub-Saharan Africa. The incidence of HIV infections in blood donations collected in the main blood banks of five countries (Burkina Faso, Congo, Ivory Coast, Mali, and Senegal) was determined to estimate the current transfusion risk of HIV infection using the incidence rate/window period model. The risk of transfusion-transmitted HIV infections associated with the window period varied from 1 in 90,200 donations (Senegal) to 1 in 25,600 (Congo). Considering the five participating blood centres as a whole, the incidence rate of HIV-positive donors per 100,000 person-years was 56.6 (95% confidence interval [CI], 47.1-67.9); the residual risk was 34.1 (95% CI, 7.8-70.7) per 1 million donations, which represents 1 in 29,000 donations (95% CI, 1/128,000-1/14,000). Residual risk estimates varied according to the country. This is potentially due to a lower incidence of HIV infection in the general population or to a more efficient selection of blood donors in the countries with the lowest risk. The estimates of the transfusion risk of HIV infection in each country are important, both to assess the impact of current preventative strategies and to contribute data to policy decisions to reinforce transfusion safety.

For abstract access click here:

Editors’ note: This is this first published study estimating the residual risk of transfusion-related HIV transmission after standard blood screening using HIV incidence among repeat donors in five sub-Saharan African countries. The result – 1 in 29,000 donations in Burkina Faso, Congo, Ivory Coast, Mali, and Senegal – contrasts markedly with the estimate for South Africa of 1 in 479,000. South Africa uses nucleic acid testing (NAT), the more expensive but efficacious option employed for blood donation screening in industrialised countries. NAT identifies donors with HIV infection who are in the pre-seroconversion window period, after infection and before HIV antibodies appear. WHO estimated in 2005 that up to 5% of HIV transmissions in sub-Saharan Africa were transfusion-related. NAT would improve transfusion safety significantly in this highest prevalence region in the world, with a cheaper interim option being some form of combination antigen/antibody testing. Regardless, it is important to strengthen donor selection by restricting donation to volunteer, unpaid, regular donors at low risk of blood-borne infections and sexually transmitted infections. Upstream prevention of blood transfusion-related HIV transmission entails avoiding unnecessary transfusions, along with prevention and timely management of anaemia caused by obstetrical haemorrhage, nutritional deficiencies, and malaria and other infections.

Progress in Global Blood Safety for HIV

Takei T, Abu Amin N, Schmid G, Dhingra-Kumar N, and Rugg D, J Acquir Immune Defic Syndr, 2009;52(S2)

The aim of the report was to assess progress towards ensuring a globally safe blood supply. The authors examined 2 global databases for blood safety: that of the United Nations General Assembly Special Session on HIV/AIDS (UNGASS) blood safety indicator; and that of the Global Database on Blood Safety (GDBS), a database developed by the World Health Organization. The UNGASS data were collected through the Ministry of Health based on the GDBS data, followed by a reconciliation and cross-checking of the data by World Health Organization and United Nations Programme on AIDS (UNAIDS). They found that the proportion of United Nations member countries reporting UNGASS data for blood safety is among the highest of all UNGASS indicators: 147 of 192 United Nations Member States participated in UNGASS reporting in 2008 and 125 of them (85%) submitted data on blood safety. Ninety-one of the 125 countries (73%) reported that 100% of collected blood units were screened in a quality assured manner, but 34 countries did not screen all collected blood units in accordance with minimum quality standards. GDBS data showed that 80.7 million blood units were collected globally in 167 countries during 2004–2005, of which 77.3 million were tested for HIV and at least 0.6 million of the remaining 3.4 million donations went untested. In conclusion, progress has been made toward eliminating blood transfusion as a significant cause of HIV infection globally. Screening all donated blood for HIV in accordance with minimum quality standards remains vital, however, as health care systems should, at a minimum, do no harm. This goal is achievable and would assist in reaching Millennium Development Goals by 2015.

For full text access click here: 1 

Editors’ note: Because receiving HIV-infected blood leads to HIV infection in 95 to 100 per cent of people who are transfused with it, ensuring the safety of blood transfusion is a highly cost-effective prevention measure at an estimated 18$ per HIV infection averted. The fact that screening all donated blood in accordance with standardised procedures in a quality assured manner is still not universal around the world is disturbing. Gaps in blood supply in some settings are endangering lives and 50% of transfusions are unnecessary in others, but it is of immediate concern that so many countries are failing to ensure safe blood for their citizens when they are in dire need. Achieving this goal is not beyond reach and will save lives.  

Ganczak M, Barss P. Nosocomial HIV infection: epidemiology and prevention-a global perspective. AIDS Rev. 2008;10(1):47-61.

Because, globally, HIV is transmitted mainly by sexual practices and injection drug use and because of a long asymptomatic period, healthcare-associated HIV transmission receives little attention even though an estimated 5.4% of global HIV infections result from contaminated injections alone. It is an important personal issue for healthcare workers, especially those who work with unsafe equipment or have insufficient training. They may acquire HIV occupationally or find themselves before courts, facing severe penalties for causing HIV infections. Prevention of blood-borne nosocomial infections such as HIV differs from traditional infection control measures such as hand washing and isolation and requires a multidisciplinary approach. Since there has not been a review of healthcare-associated HIV contrasting circumstances in poor and rich regions of the world, the aim of this article is to review and compare the epidemiology of HIV in healthcare facilities in such settings, followed by a consideration of general approaches to prevention, specific countermeasures, and a synthesis of approaches used in infection control, injury prevention, and occupational safety. These actions concentrated on identifying research on specific modes of healthcare-associated HIV transmission and on methods of prevention. Searches included studies in English and Russian cited in PubMed and citations in Google Scholar in any language. Medical Subject Headings (MeSH) keywords such as nosocomial, hospital-acquired, iatrogenic, healthcare associated, occupationally acquired infection and HIV were used together with mode of transmission, such as "HIV and haemodialysis". References of relevant articles were also reviewed. The evidence indicates that while occasional incidents of healthcare-related HIV infection in high-income countries continue to be reported, the situation in many low-income countries is alarming, with transmission ranging from frequent to endemic. Viral transmission in health facilities occurs by unexpected and unusual as well as more frequent modes. HIV can be transmitted to patients and to donors of blood products by specific vehicles and vectors during blood transfusion, plasma donation, and artificial insemination, by improperly sterilized sharps, by medical equipment during activities such as dialysis and organ transplantation, and by healthcare workers infected by occupational exposure to hazards such as blood-contaminated sharps. Personal, equipment, and environmental factors predispose to acquisition of nosocomial HIV and all are pertinent for prevention. For infection and injury control, poverty is often an underlying determinant. While sophisticated new tests offer improved HIV detection, increasingly higher marginal costs limit their feasibility in many settings. Modest investment in safer equipment and appropriate integrated training in infection control, injury prevention, and occupational safety should provide greater benefit.

Editors' note: Nosocomial (from the Greek nosos [disease] and komein [to care for] and later from the Latin for hospital nosocomium) infections are those that occur more than 48 to 72 hours after a patient is admitted and were not present or incubating at entry. This exhaustive review, the first in 15 years, is essential reading for policy makers, health personnel, and the public alike. The detailed descriptions of modes of health care-associated HIV transmission and of virtually all the documented cases from around the world set the stage for recommended interventions to eliminate/reduce risk for all countries, with special priorities for low-income countries. Arguing that prevention begins when everyone accepts that nosocomial infections are truly avoidable, the authors call for international action to develop and implement appropriate and efficient safety equipment, training, and surveillance that are feasible for even remote areas of low-income countries.

Paid plasma donation has contributed to HIV epidemics in many countries. Eleven million litres of plasma are fractionated annually in the U.S., mainly from paid donors. Deferral of high-risk donors such as injecting drug users is required for paid donations. Volkow and colleagues studied circumstances surrounding paid plasma donation among injecting drug users in two Mexico-U.S. border cities. In 2005, injecting drug users >/=18 years old in Tijuana (N=222) and Cd. Juarez (N=206) who injected in the last month were recruited through respondent-driven sampling. Subjects underwent antibody testing for HIV and HCV and an interviewer-administered survey including questions on donating and selling whole blood and plasma. Of 428 injecting drug users, HIV and HCV prevalence were 3% and 96%, respectively; 75 (17.5%) reported ever having donated/sold their blood or plasma, of whom 28 (37%) had sold their plasma for an average of $16 USD. The majority of injecting drug users selling plasma were residents of Ciudad Juarez (82%); 93% had sold their plasma only in the U.S. The last time they sold their plasma, 65% of injecting drug users had been asked if they injected drugs. Although the median time since last selling plasma was 13 years ago, 3 had done so within the prior 2 years, one within the prior 6 months; of these 3 injecting drug users, 2 were from Cd. Juarez, one from Tijuana; all 3 had only sold their plasma in the U.S. Although selling plasma appears uncommon among injecting drug users in these two Mexican border cities, the majority sold plasma in the U.S. and only one-third were deferred as high-risk donors. Paying donors for plasma should be a matter of public inquiry to encourage strict compliance with regulations. Plasma clinics should defer donors not only on behavioural risks, but should specifically inspect for injection stigmata.

Editors' note: Selling of blood and plasma was banned in Mexico over two decades ago but, surprisingly, remains legal in some US states such as California and Texas. High-risk donors are screened and deferred and pasteurisation or detergent treatment is used to inactivate potential blood-borne pathogens. Understandably, plasma donors in a paid donation system tend to be over-represented by economically disadvantaged persons who may be at higher risk of HIV exposure. Since deferral and plasma treatment are not fail-safe, all countries should move as quickly as possible to voluntary blood and plasma donations, promoted as part of civic duty rather than for monetary recompense.