HIV This Week

Butler DM, Smith DM, Cachay ER, Hightower GK, Nugent CT, Richman DD, Little SJ. Herpes simplex virus 2 serostatus and viral loads of HIV- 1 in blood and semen as risk factors for HIV transmission among men who have sex with men. AIDS. 2008;22(13):1667-71.

Human immunodeficiency virus type 1 blood plasma viral load is correlated with the sexual transmission of HIV, although transmission from men involves virus from semen instead of blood. Butler and colleagues quantified HIV-1 RNA in the blood and semen of men who did or did not transmit HIV to their sex partners. They compared the relationships of HIV-1 transmission risk with blood plasma viral load, seminal plasma viral load, herpes simplex virus 2 serostatus and other factors. In this case-control study, participants were men evaluated for primary HIV infection and their recent male sex partners. They were interviewed, and clinical specimens were collected. Epidemiologic and phylogenetic linkages were determined by history and molecular techniques. Couples were grouped on the basis of transmission after exposure. Fisher’s exact test and Wilcoxon tests were used for comparisons between groups. Multivariable logistic regressions were fit to identify independent predictors of transmission. HIV-transmitting partners (n = 15) had a higher median seminal plasma viral load (P < 0.015) and median blood plasma viral load (P < 0.001) than nontransmitting partners (n = 32). Herpes simplex virus 2 serostatus was associated with transmission only when the HIV-infected source partner was herpes simplex virus 2 seropositive and the HIV-exposed partner was not (odds ratio 16, P < 0.03). Adjusting for other factors, HIV transmission was significantly associated with blood plasma viral load (odds ratio 13.4, P < 0.02) but not seminal plasma viral load (odds ratio 0.69, P = not significant). The authors conclude that blood and seminal plasma viral load were both associated with human immunodeficiency virus type 1 transmission, but blood plasma viral load was the stronger predictor in this cohort. Herpes simplex virus 2 coinfection was associated with the risk of transmission but not acquisition of human immunodeficiency virus type 1 .

Editors’ note: Fifteen ‘transmitting’ pairs and 32 ‘non-transmitting’ pairs were compared in this study of men who have sex with men. Herpes simplex virus-2 infection was associated with transmission when the source person was co-infected but made no difference if the non-HIV-infected man was HSV-2 sero-positive. This is consistent with the negative findings from trials of herpes suppression to reduce HIV acquisition and support continuation of the trials assessing herpes suppression in co-infected people to reduce HIV transmission. The jury is still out on whether it is cell-free virus in semen (measured in seminal plasma viral load) or cell-associated virus (not measured) that increases risk of HIV transmission – in this study cell-free virus levels were associated with transmission.

Johnson LF, Lewis DA. The Effect of Genital Tract Infections on HIV-1 Shedding in the Genital Tract: A Systematic Review and Meta-Analysis. Sex Transm Dis. 2008; 35(11): 946-959 This article reviews the effect of genital tract infections and associated clinical conditions on the detection and concentration of HIV-1 shedding in the genital tract. A search of the PubMed, Embase, and AIDSearch databases was conducted. Meta-analysis was performed on those studies that reported the effect of genital tract infections on the detection of HIV-1 shedding. Thirty-nine studies met the inclusion criteria. The odds of HIV-1 detection in the genital tract were increased most substantially by urethritis (OR 3.1, 95% CI: 1.1-8.6) and cervicitis (OR 2.7, 95% CI: 1.4-5.2). The odds of HIV-1 detection were also increased significantly in the presence of cervical discharge or mucopus (OR 1.8, 95% CI: 1.2-2.7), gonorrhoea (OR 1.8, 95% CI: 1.2-2.7), chlamydial infection (OR 1.8, 95% CI: 1.1-3.1), and vulvovaginal candidiasis (OR 1.8, 95% CI: 1.3-2.4). Other infections and clinical conditions were found to have no significant effect on the detection of HIV-1, although HSV-2 shedding was found to increase the concentration of HIV-1 shedding, and genital ulcer disease was found to increase the odds of HIV-1 detection significantly after excluding one biased study ( OR 2.4, 95% CI: 1.2-4.9). This analysis shows that infections that are associated with significant increases in leukocyte concentrations in the genital tract are also associated with significant increases in HIV-1 shedding. These infections are likely to be particularly important in promoting the sexual transmission and mother-to-child intrapartum transmission of HIV-1, and should therefore be the focus of HIV prevention strategies.

Editors’ note: This systematic review and meta-analysis confirms that genital tract infections increase both the detection and the concentration of HIV-1 in the genital tract, particularly when the infection is symptomatic and recruits lots of white blood cells to the scene. Encouraging people living with HIV to recognise and seek prompt and effective treatment for genital symptoms is important in limiting HIV transmission. Various genital tract infections differ substantially in their impact on HIV shedding in the genital tract and further study is needed to determine which type of HIV shedding (proviral DNA, cell-associated RNA or cell-free RNA) is the principal determinant of HIV-1 infectiousness.

Dunne EF, Whitehead S, Sternberg M, Thepamnuay S, Leelawiwat W, McNicholl JM, Sumanapun S, Tappero JW, Siriprapasiri T, Markowitz L.Suppressive Acyclovir Therapy Reduces HIV Cervicovaginal Shedding in HIV- and HSV-2-Infected Women, Chiang Rai, Thailand. J Acquir Immune Defic Syndr. 2008 Sep 1;49(1):77-83.

Herpes simplex virus type 2 infection is important in the HIV epidemic and may contribute to increased HIV transmission. Dunne and colleagues evaluated the effect of suppressive acyclovir therapy on cervicovaginal HIV-1 shedding. HIV-1- and herpes simplex virus type 2- coinfected women aged 18-49 years with CD4 counts >200 cells/muL were enrolled in a randomized crossover trial of suppressive acyclovir therapy (NCT00362596, http://www.clinicaltrials.gov). For each woman, monthly plasma and weekly cervicovaginal lavage specimens were collected; the mean of the monthly median cervicovaginal lavage HIV-1 viral load and plasma HIV-1 viral load was compared. Sixty-seven women were enrolled; at baseline, median CD4 count was 366 cells/muL, and median HIV-1 plasma viral load was 4.6 log10 copies/mL. The mean cervicovaginal lavage HIV-1 viral load was 1.9 (SD 0.8) log10 copies/mL during the acyclovir month and 2.2 (SD 0.7) log10 copies/mL during the placebo month (P < 0.0001); the mean decrease in HIV was 0.3 log10 copies/mL. The mean plasma HIV viral load during the acyclovir month (3.78 log10 copies/mL) was reduced compared with the placebo month (4.26 log10 copies/mL, P < 0.001). Acyclovir reduced HIV genital shedding and plasma viral load among HIV-1- and herpes simplex virus type 2-coinfected women. Further data from clinical trials will examine the effct of suppressive therapy on HIV transmission.

Editors’ note: This first randomized, controlled crossover trial, meaning that women co-infected with HIV and herpes simplex virus-2 served as their own controls, found that acyclovir significantly reduced genital HIV-1 shedding. These immunocompetent women were not taking any antiretroviral drugs. Furthermore, acyclovir, which is commonly available and inexpensive, also reduced blood plasma HIV. These findings hold out promise for the trials of herpes suppression to reduce HIV transmission.

Grijsen ML, Graham SM, Mwangome M, Githua P, Mutimba S, Wamuyu L, Okuku HS, Price MA, McClelland SR, Smith AD, Sanders EJ. Screening for genital and anorectal sexually transmitted infections in HIV prevention trials in Africa. Sex Transm Infect. 2008 Mar 28 [Epub ahead of print]

Grijsen and co-authors’ objectives were (1) to demonstrate the value of routine, basic sexually transmitted infections screening at enrolment into an HIV-1 vaccine feasibility cohort study; and (2) to highlight the importance of soliciting a history of receptive anal intercourse  in adults identified as being at higher risk for HIV exposure. Routine sexually transmitted infections screening was offered to adults at higher risk for HIV-1 upon enrolment into a cohort study in preparation for HIV-1 vaccine trials. Risk behaviours and sexually transmitted infections prevalence were summarized, and the value of microscopy assessed. Associations between prevalent HIV-1 infection and receptive anal intercourse or prevalent sexually transmitted infections were evaluated with multiple logistic regression. Participants had a high burden of untreated sexually transmitted infections. Symptom-directed management would have missed 67% of urethritis cases in men and 59% of cervicitis cases in women. Receptive anal intercourse was reported by 36% of male and 18% of female participants. Receptive anal intercourse was strongly associated with HIV-1 in men (adjusted odds ratio [aOR] = 3.8, 95% CI 2.0-V 6.9), and independently associated with syphilis in women (aOR 12.9, 95% CI 3.4-V 48.7). Grijsen and colleagues conclude that high-risk adults recruited for HIV-1 prevention trials carry a high sexually transmitted infections burden.  Symptom-directed treatment may miss many cases, and simple laboratory-based screening can be done with little cost. Risk assessment should include questions about anal intercourse and whether condoms were used. Sexually transmitted infections screening, including specific assessment for anorectal disease, should be offered in African research settings recruiting participants at high risk for HIV-1 acquisition.

Editors´note: This article is about the importance of screening potential vaccine trial participants for sexually transmitted infections. But it is also about unprotected receptive anal intercourse, considered to be the most efficient mode of secual transmission of HIV, whether among men who have sex with men or heterosexual couples. If questions that are carefully worded are not asked, no answers will be given and the opportunity for intensified risk reduction counselling will be missed.

Eaton LA, Kalichman S. Risk compensation in HIV prevention: implications for vaccines, microbicides, and other biomedical HIV prevention technologies. Curr HIV/AIDS Rep. 2007;4:165-72.

Photo credit: unaids/fsanchez

Studies investigating the effects of biologic HIV prevention technologies have been reported with promising results for slowing the spread of the disease. Although they can reduce the rate of HIV transmission at varying levels of efficaciousness, it is vital to anticipate their impact on subsequent sexual behaviours. Risk homeostasis theory posits that decreases in perceived risk, which will occur with access to HIV prevention technologies, will correspond with increases in risk-taking behaviour. Here Eaton and colleagues review the literature on risk compensation in response to HIV vaccines, topical microbicides, antiretroviral medications, and male circumcision. Behavioural risk compensation is evident in response to prevention technologies that are used in advance of HIV exposure and at minimal personal cost. The authors conclude that behavioural risk compensation should be addressed by implementing adjunct behavioural risk-reduction interventions to avoid negating the preventive benefits of biomedical HIV prevention technologies.

Reducing viral load, highly active antiretroviral therapy has the potential to limit onwards transmission of HIV-1 and thus help contain epidemic spread. However, increases in risk behaviour and resurgent epidemics have been widely reported post-highly active antiretroviral therapy. The aim of this study was to quantify the impact that highly active antiretroviral therapy had on the epidemic. Bezemer and colleagues focus on the HIV-1 epidemic among men who have sex with men in the Netherlands, which has been well documented over the past 20 years within several long-standing national surveillance programs. The authors used a mathematical model including highly active antiretroviral therapy use and estimated the changes in risk behaviour and diagnosis rate needed to explain annual data on HIV and AIDS diagnoses. They show that the reproduction number R(t), a measure of the state of the epidemic, declined early on from initial values above two and was maintained below one from 1985 to 2000. Since 1996, when highly active antiretroviral therapy became widely used, risk behaviour rate has increased 66%, resulting in an increase of R(t) to 1.04 in the latest period 2000-2004 (95% confidence interval 0.98-1.09) near or just above the threshold for a self-sustaining epidemic. Hypothetical scenario analysis shows that the epidemiological benefits of highly active antiretroviral therapy and earlier diagnosis on incidence have been entirely offset by increases in the risk behaviour rate. This study provides the first detailed quantitative analysis of the HIV epidemic in a well-defined population and find a resurgent epidemic in the era of highly active antiretroviral therapy, most likely predominantly caused by increasing sexual risk behaviour.

Hirbod T, Kaul R, Reichard C, Kimani J, Ngugi E, Bwayo JJ, Nagelkerke N, Hasselrot K, Li B, Moses S; Kibera HIV Study Group, MacDonald KS, Broliden K. Collaborators: Keli F, Kamunyo G, Wanguru R, Mwakisha R, Waithira G, Nganga D, Nyambogo C, Ombette J, Njeri J, Onyango I, Malonza I, Mwangi F, Fonck K, Temmerman M, Ronald AR, Luscher M. HIV-neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers. AIDS. 2008;22(6):727-35.

HIV-neutralizing immunoglobulin A (IgA) and HIV-specific cellular immunity have been described in highly exposed, persistently seronegative individuals, but well controlled studies have not been performed. Hirbod and colleagues performed a prospective, nested case-control study to examine the association of genital IgA and systemic cellular immune responses with subsequent HIV acquisition in high-risk Kenyan female sex workers. A randomized trial of monthly antibiotic prophylaxis to prevent sexually transmitted disease/HIV infection was performed from 1998 to 2002 in HIV-uninfected Kenyan female sex workers. After the completion of trial, female sex workers who had acquired HIV (cases) were matched 1: 4 with persistently uninfected controls based on study arm, duration of HIV-seronegative follow-up, and time of cohort enrolment. Blinded investigators assayed the ability at enrolment of genital IgA to neutralize primary HIV isolates as well as systemic HIV-specific cellular IFN-gamma-modified enzyme-linked immunospot and proliferative responses. The study cohort comprised 113 female sex workers: 24 cases who acquired HIV and 89 matched controls. Genital HIV-neutralizing IgA was associated with reduced HIV acquisition (P = 0.003), as was HIV-specific proliferation (P = 0.002), and these associations were additive.  HIV-specific IFN-gamma production did not differ between case and control groups.  In multivariable analysis, HIV-neutralizing IgA and HIV-specific proliferation each remained independently associated with lack of HIV acquisition. Genital herpes (HSV2) was associated with increased HIV risk and with reduced detection of HIV-neutralizing IgA. Genital HIV-neutralizing IgA and systemic HIV-specific proliferative responses, assayed by blinded investigators, were prospectively associated with HIV nonacquisition. The induction of these immune responses may be an important goal for HIV vaccines.

Editors´note: Much is to be learned from the careful study of the immune responses of high exposed, persistently seronegative individuals, whether they are sex workers or seronegative people in long-term discordant partnerships. In this study, two independent factors were prospectively associated with reduced sexual acquisition: HIV-neutralizing immunoglobulin A (IgA) and HIV-specific proliferation in cervicovaginal lavage specimens. Herpes simplex-2 infection interfered with this partial protection by reducing HIV-neutralizing IgA in the genital tract. How to induce such protective humoral immune responses in the genital tract, whether they are associated with specific host genetics, and how they might combine with strong cellular responses are questions waiting to be answered.

Celum C, Wald A, Hughes J, Sanchez J, Reid S, Delany-Moretlwe S, Cowan F, Casapia M, Ortiz A, Fuchs J, Buchbinder S, Koblin B, Zwerski S, Rose S, Wang J, Corey L; HPTN 039 Protocol Team. Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;371(9630):2109-19.

Across many observational studies, herpes simplex virus type 2 (HSV-2) infection is associated with two-fold to three-fold increased risk for HIV-1 infection. Celum and colleagues investigated whether HSV-2 suppression with aciclovir would reduce the risk of HIV-1 acquisition. The authors undertook a double-blind, randomised, placebo-controlled phase III trial in HIV-negative, HSV-2 seropositive women in Africa and men who have sex with men from sites in Peru and the USA. Participants were randomly assigned by block randomisation to twice daily aciclovir 400 mg (n=1637) or matching placebo (n=1640) for 12-18 months, and were seen monthly for dispensation of study drug, adherence counselling and measurement by pill count and self-reporting, and risk reduction counselling, and every 3 months for genital examination and HIV testing. The primary outcome was HIV-1 acquisition and secondary was incidence of genital ulcers. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00076232. 3172 participants (1358 women, 1814 men who have sex with men) were included in the primary dataset (1581 in aciclovir group, 1591 in control group). The incidence of HIV-1 was 3.9 per 100 person-years in the aciclovir group (75 events in 1935 person-years of follow-up) and 3.3 per 100 person-years in the placebo group (64 events in 1969 person-years of follow-up; hazard ratio 1.16 [95% CI 0.83-1.62]). Incidence of genital ulcers on examination was reduced by 47% (relative risk 0.53 [0.46-0.62]) and HSV-2 positive genital ulcers by 63% (0.37 [0.31-0.45]) in the aciclovir group. Adherence to dispensed study drug was 94% in the aciclovir group and 94% in the placebo group, and 85% of expected doses in the aciclovir group and 86% in the placebo group. Retention was 85% at 18 months in both groups (1028 of 1212 in aciclovir group, 1030 of 1208 in placebo group). The authors recorded no serious events related to the study drug. Their results show that suppressive therapy with standard doses of aciclovir is not effective in reduction of HIV-1 acquisition in HSV-2 seropositive women and men who have sex with men. Novel strategies are needed to interrupt interactions between HSV-2 and HIV-1.

Editors´note: Despite well-founded epidemiological observations, biological plausibility, and mathematical modelling, a protective effect of herpes suppression was not found in this large trial nor in a smaller, similar study in Tanzania (Watson-Jones, Weiss, Rusizoka et al. N Engl J Med. 2008;358(15):1560-71). Studies are ongoing to assess whether co-infected (HIV-1, HSV-2) individuals in serodiscordant couples are less likely to transmit HIV if they achieve HSV-2 suppression and have slower HIV disease progression. Nevertheless, an effective herpes simplex virus vaccine is urgently needed.

Kristin L Dunkle, Rob Stephenson, Etienne Karita, Elwyn Chomba, Kayitesi Kayitenkore, Cheswa Vwalika, Lauren Greenberg, Susan Allen. New heterosexually transmitted HIV infections in married or cohabiting couples in urban Zambia and Rwanda: an analysis of survey and clinical data. Lancet. 2008;371(9631):2183-91.

Sub-Saharan Africa has a high rate of HIV infection, most of which is attributable to heterosexual transmission. Few attempts have been made to assess the extent of HIV transmission within marriages, and HIV prevention efforts remain focused on abstinence and non-marital sex. Dunkle and colleagues aimed to estimate the proportion of heterosexual transmission of HIV which occurs within married or cohabiting couples in urban Zambia and Rwanda each year. The authors used population-based data from Demographic and Health Surveys (DHS) on heterosexual behaviour in Zambia in 2001–02 and in Rwanda in 2005, as well as used data on the HIV serostatus of married or cohabiting couples and non-cohabiting couples that was collected through a voluntary counselling and testing service for urban couples in Lusaka, in Zambia, and Kigali, in Rwanda. They estimated the probability that an individual would acquire an incident HIV infection from a cohabiting or non-cohabiting sexual partner, and then the proportion of total heterosexual HIV transmission which occurs within married or cohabiting couples in these settings each year. DHS data from 1739 Zambian women, 540 Zambian men, 1176 Rwandan women, and 606 Rwandan men was analyzed. Under the base model, the authors estimated that 55·1% to 92·7% of new heterosexually acquired HIV infections among adults in urban Zambia and Rwanda occurred within serodiscordant marital or cohabiting relationships, depending on the sex of the index partner and on location. Under the extended model, which incorporated the higher rates of reported condom use that were found with non-cohabiting partners, the authors estimated that 60·3% to 94·2% of new heterosexually acquired infections occurred within marriage or cohabitation. An intervention for couples which reduced transmission in serodiscordant urban cohabiting couples from 20% to 7% every year could avert 35·7% to 60·3% of heterosexually transmitted HIV infections that would otherwise occur. Since most heterosexual HIV transmission for both men and women in urban Zambia and Rwanda takes place within marriage or cohabitation, voluntary counselling and testing for couples should be promoted, as should other evidence-based interventions that target heterosexual couples.

Editors´note: With three-quarters of HIV-infected adults in sub-Saharan Africa unaware of their HIV status and high levels of marital serodiscordance, marriage or cohabitation poses a risk for both men and women. Promoting fidelity for couples without accompanying HIV testing can result in a 20% annual transmission rate. Scale-up of couple-based counselling and testing accompanied by support for marital disclosure and plans for risk reduction, antiretroviral treatment and preventive care for the infected partner, and male circumcision for HIV-negative men is urgently needed.

van Sighem A, Zhang S, Reiss P, Gras L, van der Ende M, Kroon F, Prins J, de Wolf F; on Behalf of the ATHENA National Observational Cohort Study. Immunologic, Virologic, and Clinical Consequences of Episodes of Transient Viraemia During Suppressive Combination Antiretroviral Therapy. J Acquir Immune Defic Syndr. 2008 May 1;48(1):104-8.

van Sighem and colleagues aimed to investigate immunologic, virologic, and clinical consequences of episodes of transient viraemia in patients with sustained virologic suppression. From the AIDS Therapy Evaluation Project, Netherlands cohort, 4447 previously therapy-naive patients were selected who were on continuous combination antiretroviral therapy and had initial success (2 consecutive HIV RNA measurements <50 copies/mL). During episodes of viral suppression (RNA <50 copies/mL), low-level viraemia (RNA 50 to 1000 copies/mL), or high-level viraemia (RNA >1000 copies/mL) after initial success, the occurrence of therapy changes, drug resistance, and clinical events was assessed. During 11,187 person-years of follow-up, 1281 (28.8%) patients had at least 1 RNA measurement >50 copies/mL. Among 8069 episodes, there were 5989 (74.2%) episodes of suppression, 1711 (21.2%) episodes of low-level viraemia, and 369 (4.6%) episodes of high-level viraemia. Most episodes of low-level viraemia consisted of </=2 RNA measurements (93.7%), were without clinical events or therapy changes (79.6%), and were without changes in CD4 cell counts. Therapy changes (52.3% of episodes) and resistance (23.3%) were frequently observed during high-level viraemia. In conclusion, episodes of low-level viraemia are frequent and short-lasting, and the low proportion of episodes with clinical events suggests that leaving therapy unchanged is a clinically acceptable strategy. In contrast, high-level viraemia is associated with resistance and is often followed by therapy changes.

Editors´note: Although the focus here is on whether viraemia should be an indication for a change in therapy, viraemia in previously naive patients on treatment has potential relevance for transmission risk. A high proportion of patients were viraemic during winter when influenza and the common cold are more prevalent, suggesting that antigenic stimulation due to other infections may play a role. Thus, although effective antiretroviral treatment reduces viral load, blips can still occur – 28.8% of continuously treated patients in this large-cohort experienced at least one transient episode of viraemia.

Kwara A, Delong A, Rezk N, Hogan J, Burtwell H, Chapman S, Moreira CC, Kurpewski J, Ingersoll J, Caliendo AM, Kashuba A, Cu-Uvin S. Antiretroviral drug concentrations and HIV RNA in the genital tract of HIV-infected women receiving long-term highly active antiretroviral therapy. Clin Infect Dis. 2008;46(5):719-25.

Kwara and colleagues aimed to determine antiretroviral drug concentrations and human immunodeficiency virus (HIV) RNA rebound in cervicovaginal fluid in relation to blood plasma in women receiving suppressive highly active antiretroviral therapy. Thirty-four HIV-infected women who had plasma HIV RNA levels < or =80 copies/mL for at least 6 months were enrolled. Sixty-eight paired cervicovaginal fluid  and blood plasma  drug concentrations and HIV RNA levels were determined before and 3-4 h after drug administration. For each woman and antiretroviral drug, the cervicovaginal fluid:blood plasma  drug concentration ratios before and after drug administration were calculated. The nonparametric Wilcoxon rank sum test was used to determine if these ratios were different from 1.0. Lamivudine (administered to 20 patients) and tenofovir (administered to 16) had significantly higher concentrations in cervicovaginal fluid than in blood plasma  before drug administration, with mean cervicovaginal fluid:blood plasma  concentration ratios of 3.19 (95% confidence interval, 1.2-8.5) and 5.2 (95% confidence interval, 1.2-22.6), respectively. Efavirenz (administered to 13 patients) and lopinavir (administered to 6) had significantly lower concentrations in cervicovaginal fluid, with mean cervicovaginal fluid:blood plasma  concentration ratios of 0.01 (95% confidence interval, 0.00-0.03) and 0.03 (0.01-0.11), respectively. During the study visit (median time after enrolment, 6 months), blood plasma  and cervicovaginal fluid detectable HIV RNA levels were observed 7 patients (20.6%) and 1 patient (2.9%), respectively. Despite lower cervicovaginal fluid concentrations of key antiretroviral therapy components, such as efavirenz and lopinavir, virologic rebound was rare. The high concentrations of tenofovir and lamivudine in cervicovaginal fluid may have implications for the prevention of sexual transmission during antiretroviral therapy and for pre-exposure or post-exposure prophylaxis.

Editors´note: Both non-nucleoside reverse transcriptase inhibitors and protease inhibitors penetrate poorly into the genital tract achieving concentrations from 3 to 33% of their concentrations in paired blood plasma. Whether this creates the equivalent of local suboptimal therapy which could lead to genital tract viral drug resistance is not known. The good news is that the nucleoside reverse transcriptase inhibitors that form the backbone of combination therapy not only accumulate but actually concentrate in cervicovaginal fluid, which could have implications for prevention of onward HIV transmission.

Belza MJ, de la Fuente L, Suárez M, Vallejo F, García M, López M, Barrio G, Bolea A; Health And Sexual Behaviour Survey Group. Men who pay for sex in Spain and condom use: prevalence and correlates in a representative sample of the general population. Sex Transm Infect. 2008;84:207–211.

Belza and colleagues aimed to estimate the percentage of men who have paid for heterosexual sex in Spain and the percentage who used condoms. They aimed to identify the main factors associated with these behaviours and to describe opinions about condoms. Sexual behaviour probability sample survey in men aged 18–49 years resident in Spain in 2003 (n=5153). Computer-assisted face to face and self interview was used. Bivariate and multivariate logistic regression analyses were performed. 25.4% (n=1306) of the men had paid for heterosexual sex at some time in their lives; 13.3% (n=687) in the last 5 years and 5.7% (n=295) in the last 12 months. In the logistic analysis this behaviour was associated with older age, lower education, being unmarried, foreign birth, being a practicing member of a religious group, unsatisfactory communication with parents about sex, age under 16 years at first sexual intercourse and having been drunk in the last 30 days. Of the men who had paid for sex in the previous 5 years, 95% (n=653) had used a condom in the most recent paid contact. In the multivariate analysis, not using a condom was associated with age over 30 years and first sexual intercourse before age 16 years. Men who did not use condoms in the last commercial intercourse had more negative opinions about condoms. In conclusion, the prevalence of paying for heterosexual sex among Spanish men is the highest ever described in developed countries. The many variables associated with paying for sex and condom use permit the characterisation of male clients of prostitution and should facilitate targeting HIV prevention policies.

Editors´note: There have been many studies of female sex workers but little research on the prevalence of paying for sex in the general male population. This study is intriguing not only because condom use in these encounters is so high but because a quarter of men have paid for sex at some point in their lives. Aside from a number of expected associations, logistical regression found that practicing members of a religious group (94.4% of whom were Catholic) – defined as attending religious services once a week or more - had a higher prevalence of commercial sex relations and were less likely to use condoms in these encounters.

Abu-Raddad LJ, Magaret AS, Celum C, Wald A, Longini IM Jr, Self SG, Corey L. Genital herpes has played a more important role than any other sexually transmitted infection in driving HIV prevalence in Africa. PLoS ONE. 2008; 3(5):e2230.

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. The results suggest a more substantial role for HSV-2 in fuelling HIV spread in sub-Saharan Africa than other sexually transmitted infections. Abu-Raddad and colleagues 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 Cities study. Conversely, the authors estimate that HIV had only a small net impact on HSV-2 prevalence. In conclusion, HSV-2’s 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.

Editors’ note: The herpes simplex-2 (HSV-2) epidemic in sub-Saharan Africa appears to have started in the first half of the twentieth century and reached its peak at about 50% prevalence prior to the HIV epidemic. Now the two viruses are happy bedfellows with HSV-2 increasing HIV acquisition and transmission more than HIV increases HSV-2 acquisition and transmission. This synergy has allowed HIV to reach a higher proportion of the general population than would have been possible without this biological interaction. An effective HSV-2 vaccine is urgently needed to protect all young people in established epidemics before sexual debut, but there is no doubt that it would be beneficial worldwide.

Lingappa JR, Lambdin B, Bukusi EA, Ngure K, Kavuma L, Inambao M, Kanweka W, Allen S, Kiarie JN, Makhema J, Were E, Manongi R, Coetzee D, de Bruyn G,Delany-Moretlwe S, Magaret A, Mugo N, Mujugira A, Ndase P, Celum C; for the Partners in Prevention HSV-2/HIV Transmission Study Group. Regional Differences in Prevalence of HIV-1 Discordance in Africa and Enrollment of HIV-1 Discordant Couples into an HIV-1 Prevention Trial. PLoS ONE. 2008; 3(1):e1411.

Most HIV-1 transmission in Africa occurs among HIV-1-discordant couples (one partner HIV-1 infected and one uninfected) who are unaware of their discordant HIV-1 serostatus. Given the high HIV-1 incidence among HIV-1 discordant couples and to assess efficacy of interventions for reducing HIV-1 transmission, HIV-1 discordant couples represent a critical target population for HIV-1 prevention interventions and prevention trials. Substantial regional differences exist in HIV-1 prevalence in Africa, but regional differences in HIV-1 discordance among African couples, has not previously been reported. The Partners in Prevention herpes simplex virus type 2 (HSV-2)/HIV-1 Transmission Trial (”Partners HSV-2 Study”), the first large HIV-1 prevention trial in Africa involving HIV-1 discordant couples, completed enrolment in May 2007. Partners HSV-2 Study recruitment data from 12 sites from East and Southern Africa were used to assess HIV-1 discordance among couples accessing couples HIV-1 counselling and testing, and to correlate with enrolment of HIV-1 discordant couples. HIV-1 discordance at Partners HSV-2 Study sites ranged from 8-31% of couples tested from the community. Across all study sites and, among all couples with one HIV-1 infected partner, almost half (49%) of couples were HIV-1 discordant. Site-specific monthly enrolment of HIV-1 discordant couples into the clinical trial was not directly associated with prevalence of HIV-1 discordance, but was modestly correlated with national HIV-1 counselling and testing rates and access to palliative care/basic health care (r = 0.74, p = 0.09). In conclusion, HIV-1 discordant couples are a critical target for HIV-1 prevention in Africa. In addition to community prevalence of HIV-1 discordance, national infrastructure for HIV-1 testing and healthcare delivery and effective community outreach strategies impact recruitment of HIV-1 discordant couples into HIV-1 prevention trials.

Editors’ note: In the screening phase for a large trial assessing the impact of herpes simplex-2 (HSV-2) suppression with acyclovir in co-infected (HIV-1, HSV-2) partners of HIV-negative, HSV-2 negative people, 51,900 couples were tested. Among all the couples tested in which HIV infection was found, 36 to 85% of them, depending on the study site, were discordant with an overall rate of 49%. Because discordant couples are such an important population for HIV prevention (in reality, HIV prevalence is 50% in the couple’s bed), community mobilisation to encourage couples to be tested as couples, rather than as individuals, and to provide social support to couples who learn their discordant or positive concordant status is an urgent public health priority.

Deveaux L, Stanton B, Lunn S, Cottrell L, Yu S, Brathwaite N, Li X, Liu H, Marshall S, Harris C. Reduction in human immunodeficiency virus risk among youth in developing countries. Arch Pediatr Adolesc Med. 2007; 161(12):1130-9.

Deveaux and colleagues address the 6-month efficacy of a human immunodeficiency virus (HIV) prevention intervention targeted to youth and delivered with and without a parental monitoring intervention in a developing country (the Bahamas). The authors conduct a randomized, controlled, 3-cell intervention trial with a 6-month postintervention follow-up in a total of 1282 Bahamian sixth-grade students ( and 1175 parents) in 15 elementary schools in the Bahamas. Youth and parents were randomized at the level of the school to receive the following interventions: (1) Focus on Youth in the Caribbean (FOYC) plus Caribbean Informed Parents and Children Together (CImPACT), (2) FOYC plus an attention control for parents (Goal for It [GFI]), or (3) an attention control for the youth (Wonderous Wetlands [WW]) plus the GFI. The 10-session FOYC or WW curriculum was delivered as part of the elementary school curriculum. The GFI or CImPACT was delivered to parents in the evenings or on weekends. Risk and protective knowledge, condom use skills, perceptions, interventions, and self-reported behaviours were measured. Compared with the WW, the FOYC significantly increased knowledge, condom use skills, protective perceptions, and intentions to engage in safer behaviours. Among youth, no differences were found in knowledge or condom use skills based on parent intervention; among parents, those receiving the CImPACT demonstrated superior condom use skills after the intervention. In conclusion, protective knowledge, skills, perceptions, and intentions of youth from one developing country can be significantly improved by youth intervention delivered through the schools. Longer follow-up is needed to determine if risk behaviours will be reduced and how long protective results will be sustained.

Editors’ note: It is not surprising that a 10-chapter theory-based school-based HIV intervention emphasising skill development, practice in negotiation, and communication/decision-making had greater effects on knowledge and intentions to practice sexual protective behaviour than a 10-chapter curriculum emphasising the importance of water conservation, wild life, and other natural resources in the Bahamas. What is surprising is that there was no difference in adolescent scores when their parents participated in ImPACT, a parental monitoring and communication intervention that had been effective in the USA in reducing adolescent HIV risk behaviours when combined with a similar adolescent risk reduction intervention, compared to a control intervention for parents (a 20 minute video about career goals). The most likely explanation may be that ImPACT, which included a condom demonstration, was modified for the Bahamas for delivery only to parents and not to parents and youth together. The opportunity was missed to foster the parental-adolescent communication that can make all the difference.

Sikkema KJ, Wilson PA, Hansen NB, Kochman A, Neufeld S, Ghebremichael MS, KershawT. Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse. J Acquir Immune Defic Syndr. 2008; 47(4):506-13.

Sikkema and colleagues examine the effect of a 15-session coping group intervention compared with a 15-session therapeutic support group intervention among HIV-positive men and women with a history of childhood sexual abuse on sexual transmission risk behaviour. In a randomized controlled behavioural intervention trial with 12-month follow-up, a diverse sample of 247 HIV-positive men and women with histories of childhood sexual abuse was randomized to 1 of 2 time-matched group intervention conditions. Sexual behaviour was assessed at baseline; immediately after the intervention; and at 4-, 8-, and 12-month follow up periods (5 assessments). Changes in frequency of unprotected anal and vaginal intercourse by intervention condition were examined using generalized linear mixed models for all partners, and specifically for HIV-negative or serostatus unknown partners. Participants in the HIV and trauma coping intervention condition decreased their frequency of unprotected sexual intercourse more than participants in the support intervention condition for all partners (P < 0.001; d = 0.38, 0.32, and 0.38 at the 4-, 8-, and 12-month follow-up periods, respectively) and for HIV-negative and serostatus unknown partners (P < 0.001; d = 0.48, 0.39, and 0.04 at the 4-, 8-, and 12-month follow-up periods, respectively). The authors conclude that a group intervention to address coping with HIV and childhood sexual abuse can be effective in reducing transmission risk behaviour among HIV-positive men and women with histories of sexual trauma.

Editors’ note: From one-third to two-thirds of people living with HIV in the USA report a history of having been sexually abused as children, more than double the estimated rates in the general population. The association between childhood sexual abuse and sexual risk behaviours is well documented. The participants randomised to the coping group intervention benefited from adaptive coping skills building for confronting the combined stress and emotional consequences of child sexual abuse and HIV. Focusing on psychological adjustment and development of adaptive coping skills had a significantly greater effect on safer sex practices than a therapeutic support group and probably had similar unmeasured effects on coping in other areas of life.

Russell TV, Do AN, Setik E, Sullivan PS, Rayle VD, Fridlund CA, Quan VM, Voetsch AC, Fleming PL. Sexual Risk Behaviors for HIV/AIDS in Chuuk State, Micronesia: The Case for HIV Prevention in Vulnerable Remote Populations. PLoS ONE. 2007; 2(12):e1283.

After the first two cases of locally-acquired HIV infection were recognized in Chuuk State, Federated States of Micronesia, a public health response was initiated. The purpose of the response was to assess the need for HIV education and prevention services, to develop recommendations for controlling further spread of HIV in Chuuk, and to initiate some of the prevention measures. A public health team conducted a survey and rapid HIV testing among a sample of residents on the outer islands in Chuuk. Local public health officials conducted contact tracing and testing of sex partners of the two locally-acquired cases of HIV infection. A total of 333 persons completed the survey. The majority knew that HIV is transmitted through unprotected sexual contact (81%), injection drug use (61%), or blood transfusion (64%). Sexual activity in the past 12 months was reported among 159 participants, including 90 females and 69 males. Compared to women, men were more likely to have had multiple sex partners, to have been drunk during sex, but less likely to have used a condom in the past 12 months. The two men with locally acquired HIV infection had unprotected anal sex with a third Chuukese man who likely contracted HIV while outside of Chuuk. All 370 persons who received voluntary, confidential HIV counselling and testing had HIV negative test results. Despite the low HIV seroprevalence, risky sexual behaviours in this small isolated population raise concerns about the potential for rapid spread of HIV. The lack of knowledge about risks, along with stigmatizing attitudes towards persons infected with HIV and high risk sexual behaviours indicate the need for resources to be directed toward HIV prevention in Chuuk and on other Pacific Islands.

Editors’ note: With only 1500 residents living on this small group of islands, confidentiality would not have been maintained if classical “contact tracing and testing of sex partners”, as implied by the abstract, had occurred. The innovation was for local village officials to convene a public meeting on each of the four islands to explain general health outreach activities, including the offer of HIV testing and counselling. When known contacts of either of the two index cases came forward for HIV testing, health department staff notified them of their potential exposure and provided expanded counselling on HIV risk reduction, without loss of confidentiality. Geographic isolation does not protect people from HIV and the constraints to respecting confidentiality in small populations need to be overcome creatively, as was done here.

Zungu-Dirwayi N, Shisana O, Louw J, Dana P. Social determinants for HIV prevalence among South African educators. AIDS Care. 2007; 19(10):1296-303.

HIV prevalence among women in South Africa continues to be high despite the availability of a comprehensive plan for the control of HIV and a plethora of prevention programmes. Any explanation for the ongoing high HIV prevalence continues to be elusive. The objective of this study was to understand the relationship between HIV, gender, race, and socioeconomic status among South African public sector educators in order to inform prevention programmes. A cross-sectional survey involving a probability sample of 1,766 schools out of 26,713 in the Department of Education Register of School Needs was selected. A sample of 24,200 respondents out of 356,749 public sector educators participated in the study. Nurses registered with the South African Nursing Council were recruited, trained to conduct interviews and to collect specimens for HIV testing. The study found an association between HIV, gender, race, and socioeconomic status among educators. African educators showed a higher HIV prevalence than other race groups. Among females, the highest HIV prevalence was among educators aged 25-35 years and in males aged 36-49 years. Further, educators with a high income and educational qualifications had a lower HIV prevalence compared to educators with low income and low educational qualifications, regardless of sex. Migration and marital factors were also found to play a role in HIV infection. The results suggest that HIV prevention needs to take into account critical issues around empowerment of vulnerable groups such as women and certain race groups to be able to implement safe sexual practices and therefore reduce HIV infections.

Editors’ note: Nearly 13% of all educators were HIV-positive in this study, a tremendous toll for any educational system. HIV prevalence in women who began teaching being married (14.7%) or engaged (11.4%) was lower than that among those who began their career being single (25.4%). Prevention programmes for young, single, female educators who are mobile are urgently needed. Educators of both sexes who were placed away from their families on completion of their studies had a significantly higher HIV prevalence. School boards need to consider the advantages of keeping teachers’ families with them to preserve mid-to-long term teaching capacity.

This study examined the role of hunger and food insecurity in the sexual behaviour of female sex workers in Lagos metropolis, Nigeria within the context of HIV. In addition, the study investigated the prevalence of sexually transmitted infections and induced abortion among the respondents. Cross-sectional survey and in-depth interview research methods were adopted to generate both quantitative and qualitative data from the respondents. The study showed that 35.0% of the respondents joined the sex industry because of poverty and lack of other means of getting daily food. While all the respondents had knowledge about the existence of HIV and AIDS, 82.0% of them identified sexual intercourse as a major route of HIV transmission. There was a significant relationship between poverty, food insecurity, and consistent use of condoms by female sex workers at P<0.01. Specifically, only 24.7% of the respondents used condoms regularly in every sexual act. Consequently, 51.6% had previous cases of sexually transmitted infections. The most prevalent sexually transmitted infection among the respondents was gonorrhoea, with 76.4% prevalence among ever infected female sex workers. This was followed by syphilis with a prevalence of 21.1%. In addition, 59.1% of the sample had become pregnant while on the job and 93.1% of these pregnancies were aborted through induced abortion. In conclusion, hunger and malnutrition were the factors that pushed young women into prostitution in Nigeria and these same factors hindered them from practicing safe sex within the sex industry. Thus, it is recommended that the Nigerian government should develop programmes that will reduce hunger and food insecurity, in order to reduce rapid transmission of HIV infection in the country.

Editors’ note: The links between hunger, food insecurity, and vulnerability to HIV described by this article are brought into sharp relief by the current global food crisis. Improving local food production to meet basic food needs not only helps reduce poverty levels; it pulls the rug out from under food insecurity as a driver of the HIV epidemic.