Neutralizing Activity of Broadly Neutralizing anti-HIV-1 Antibodies against Primary African Isolates.

Novel therapeutic and preventive strategies are needed to contain the HIV-1 epidemic. Broadly neutralizing human antibodies (bNAbs) with exceptional activity against HIV-1 are currently being tested in HIV-1 prevention trials. The selection of anti-HIV-1 bNAbs for clinical development was primarily guided by their in vitro neutralizing activity against HIV-1 Env pseudotyped viruses. Here we report on the neutralizing activity of 9 anti-HIV-1 bNAbs now in clinical development against 126 Clade A, C, D PBMC-derived primary African isolates. The neutralizing potency and breadth of the bNAbs tested was significantly reduced compared to pseudotyped viruses panels. The difference in sensitivity between pseudotyped viruses and primary isolates varied from 3- to nearly 100-fold depending on the bNAb and the HIV-1 clade. Thus, the neutralizing activity of bNAbs against primary African isolates differs from their activity against pseudovirus panels. The data have significant implications for interpreting the results of ongoing HIV-1 prevention trials.IMPORTANCE HIV remains a major public health problem worldwide, and new therapies and preventive strategies are necessary for controlling the epidemic. Broadly neutralizing antibodies (bNAbs) have been developed in the past decade to fill this gap. The neutralizing activity of these antibodies against diverse HIV strains has mostly been measured using Env-pseudotyped viruses, which overestimate bNAb coverage and potency. In this study we measured the neutralizing activity of nine bNAbs against clade A, C, and D HIV isolates derived from cells of African patients living with HIV and produced in peripheral blood mononuclear cells. We found that the coverage and potency of bNAbs were often significantly lower than what was predicted by Env-psuedotyped viruses, and that this decrease was related to the bNAb biding site class. This data is important for the planning and analysis of clinical trials that seek to evaluate bNAbs for the treatment and prevention of HIV infection in Africa.

Family influences on oral PrEP use among adolescent girls and young women in Kenya and South Africa.

INTRODUCTION: Effective use of oral HIV pre-exposure prophylaxis (PrEP) has been lower among African adolescent girls and young women (AGYW) than among older women, young men who have sex with men, and serodiscordant heterosexual couples in the region. Efforts to build PrEP support have centered around peers and male partners, but the family may also play an important role. This qualitative study aimed to describe family influence on PrEP use among AGYW in in three African cities. METHODS: POWER (Prevention Options for Women Evaluation Research) was a PrEP demonstration project among 2550 AGYW (16-25 years old) in Johannesburg and Cape Town, South Africa and Kisumu, Kenya conducted from 2017 to 2020. In-depth interviews and focus group discussions were conducted with 136 AGYW participants to explore their PrEP views and experiences, including awareness and interest in PrEP; barriers and facilitators to uptake and use; the influence of family, peers, intimate partners, and community; and the key types of support for their PrEP use. Transcripts were coded and analysed thematically. RESULTS: The decision to initiate PrEP was associated with fear and anxiety linked to anticipated stigma from family members, and with family's lived HIV experience. Family disclosure, especially to mothers, was important to participants, as most lived with their families and considered it essential for them to obtain their mother's approval to use PrEP. Most family members, particularly mothers, provided instrumental, emotional, informational and appraisal support to participants using PrEP, including reminders, encouragement, and problem-solving. Participants reported that family members with insufficient information about PrEP safety and efficacy and who voiced concerns were a substantial barrier to their use. However, they often became supportive after receiving more PrEP information. CONCLUSION: Families, particularly mothers, can play an important role in supporting PrEP use. PrEP programmes should leverage family support to help with PrEP persistence by providing basic information to families about PrEP safety and efficacy. AGYW using PrEP should be encouraged to selectively disclose PrEP use to build support and counseled on how to disclose and address family concerns.

Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples.

BACKGROUND: Bacterial vaginosis (BV), a disruption of the normal vaginal flora, has been associated with a 60% increased risk of HIV-1 acquisition in women and higher concentration of HIV-1 RNA in the genital tract of HIV-1-infected women. However, whether BV, which is present in up to half of African HIV-1-infected women, is associated with an increase in HIV-1 transmission to male partners has not been assessed in previous studies. METHODS AND FINDINGS: We assessed the association between BV on female-to-male HIV-1 transmission risk in a prospective study of 2,236 HIV-1-seropositive women and their HIV-1 uninfected male partners from seven African countries from a randomized placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus (HSV)-2, and their HIV-1-seronegative partners. Participants were followed for up to 24 months; every three months, vaginal swabs were obtained from female partners for Gram stain and male partners were tested for HIV-1. BV and normal vaginal flora were defined as a Nugent score of 7-10 and 0-3, respectively. To reduce misclassification, HIV-1 sequence analysis of viruses from seroconverters and their partners was performed to determine linkage of HIV-1 transmissions. Overall, 50 incident HIV-1 infections occurred in men in which the HIV-1-infected female partner had an evaluable vaginal Gram stain. HIV-1 incidence in men whose HIV-1-infected female partners had BV was 2.91 versus 0.76 per 100 person-years in men whose female partners had normal vaginal flora (hazard ratio 3.62, 95% CI 1.74-7.52). After controlling for sociodemographic factors, sexual behavior, male circumcision, sexually transmitted infections, pregnancy, and plasma HIV-1 RNA levels in female partners, BV was associated with a greater than 3-fold increased risk of female-to-male HIV-1 transmission (adjusted hazard ratio 3.17, 95% CI 1.37-7.33). CONCLUSIONS: This study identified an association between BV and increased risk of HIV-1 transmission to male partners. Several limitations may affect the generalizability of our results including: all participants underwent couples HIV counseling and testing and enrolled in an HIV-1 prevention trial, and index participants had a baseline CD4 count ≥ 250 cells/mm³ and were HSV-2 seropositive. Given the high prevalence of BV and the association of BV with increased risk of both female HIV-1 acquisition and transmission found in our study, if this association proves to be causal, BV could be responsible for a substantial proportion of new HIV-1 infections in Africa. Normalization of vaginal flora in HIV-1-infected women could mitigate female-to-male HIV-1 transmission. TRIAL REGISTRATION: ClinicalTrials.com NCT00194519.

Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study.

BACKGROUND: Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART) for HIV-1-infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP) for HIV-1-uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected) are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed. METHODS AND FINDINGS: We constructed a mathematical model to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples. Although the cost of PrEP is high, the cost per infection averted is significantly offset by future savings in lifelong treatment, especially among couples with multiple partners, low condom use, and a high risk of transmission. In some situations, highly effective PrEP could be cost-saving overall. To keep couples alive and without a new infection, providing PrEP to the uninfected partner could be at least as cost-effective as initiating ART earlier in the infected partner, if the annual cost of PrEP is <40% of the annual cost of ART and PrEP is >70% effective. CONCLUSIONS: Strategic use of PrEP and ART could substantially and cost-effectively reduce HIV-1 transmission in HIV-1 serodiscordant couples. New and forthcoming data on the efficacy of PrEP, the cost of delivery of ART and PrEP, and couples behaviours and preferences will be critical for optimizing the use of antiretrovirals for HIV-1 prevention. Please see later in the article for the Editors' Summary.

Daily acyclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial.

BACKGROUND: Most people infected with HIV-1 are dually infected with herpes simplex virus type 2. Daily suppression of this herpes virus reduces plasma HIV-1 concentrations, but whether it delays HIV-1 disease progression is unknown. We investigated the effect of acyclovir on HIV-1 progression. METHODS: In a trial with 14 sites in southern Africa and east Africa, 3381 heterosexual people who were dually infected with herpes simplex virus type 2 and HIV-1 were randomly assigned in a 1:1 ratio to acyclovir 400 mg orally twice daily or placebo, and were followed up for up to 24 months. Eligible participants had CD4 cell counts of 250 cells per mL or higher and were not taking antiretroviral therapy. We used block randomisation, and patients and investigators were masked to treatment allocation. Effect of acyclovir on HIV-1 disease progression was defined by a primary composite endpoint of first occurrence of CD4 cell counts of fewer than 200 cells per microL, antiretroviral therapy initiation, or non-trauma related death. As an exploratory analysis, we assessed the endpoint of CD4 falling to <350 cells per microL. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00194519. FINDINGS: At enrollment, the median CD4 cell count was 462 cells per microL and median HIV-1 plasma RNA was 4.1 log(10) copies per microL. Acyclovir reduced risk of HIV-1 disease progression by 16%; 284 participants assigned acyclovir versus 324 assigned placebo reached the primary endpoint (hazard ratio [HR] 0.84, 95% CI 0.71-0.98, p=0.03). In those with CD4 counts >or=350 cells per microL, aciclovir delayed risk of CD4 cell counts falling to <350 cells per microL by 19% (0.81, 0.71-0.93, p=0.002) INTERPRETATION: The role of suppression of herpes simplex virus type 2 in reduction of HIV-1 disease progression before initiation of antiretroviral therapy warrants consideration. FUNDING: Bill & Melinda Gates Foundation.

Women's perceptions and experiences of HIV prevention trials in Soweto, South Africa.

Persistently high rates of HIV infection in sub-Saharan Africa have driven the exploration for additional methods of prevention, such as microbicides. Multi-site, field-based clinical trials of microbicides are conducted in diverse social and cultural contexts. Local social and cultural perceptions of HIV/AIDS and sexual risk can have profound implications in shaping community responses to the clinical trials, thereby affecting enrollment and retention. Moreover, clinical trials may have a significant impact on trial participants with regard to their views of AIDS, health and relationships. Following these issues, this paper explores the subjective experiences of women enrolled in a microbicide feasibility study. Qualitative data were collected in two phases. The first phase took place prior to the inception of the feasibility study. Men and women from Soweto participated in focus group discussions about their perceptions and experiences of the AIDS epidemic and sexual risk. The second phase started once enrollment into the feasibility study had begun. Twenty-one women who were enrolled in the microbicide feasibility study were interviewed and participated in focus groups, and were asked about their experiences of participating in the microbicide feasibility study. Special attention was placed on how they felt their participation had affected their everyday lives. Interviews and discussions were conducted in local languages, recorded, translated and transcribed. Data were analysed thematically. The central finding of this study is the sense of empowerment that feasibility study participants felt in spite of their being embedded in a culture that has come to fear, deny or ignore AIDS. We discuss the critical role of repeated, voluntary counselling and testing, knowledge of HIV status, and heightened awareness of sexual and reproductive health in reshaping study participants' approaches to sexual relationships and AIDS, as well as the benefits that participation entailed.

Injectable progestin contraceptive use and risk of HIV infection in a South African family planning cohort.

OBJECTIVE: To investigate whether the incidence of HIV infection is higher among sexually active women using depot medroxyprogesterone acetate (DMPA) or noresthisterone enanthate (NET-EN) injections for contraception than among women using nonhormonal or no contraception. METHODS: Five hundred and fifty-one initially HIV-negative women were followed up for a total of 491 person-years. Participants were interviewed, counselled, examined, tested for HIV and other STIs, and treated, at three monthly intervals for 1 year. RESULTS: There was no significant association between progestin contraceptive use and HIV infection (rate ratio 1.1, 95% CI 0.5 to 2.8; log-rank test, p=.73). In proportional hazards regression, the only significant hazard ratios for HIV acquisition were prevalent Neisseria gonorrhoea (5.2; 95% CI 1.1 to 23.7, p=.035) and Trichomonas vaginalis (4.8; 95% CI 1.0 to 22.8, p=.049); bacterial vaginosis was marginally significant (2.8; 95% CI 1.0 to 8.3, p=.057). The adjusted hazard ratios for NET-EN and DMPA were 1.76 (95% CI 0.64 to 4.84) and 0.46 (95% CI 0.06 to 3.79), respectively, relative to nonuse. Five hundred and twelve of 551 women had one or more confirmed STIs during the study. CONCLUSIONS: There is no evidence of an association between HIV infection and injectable contraceptives. Due to the limited power of this study and because similar studies have not included young women using NET-EN, we recommend that further research be carried out to focus on the use of NET-EN and HIV acquisition in high risk groups.

Microbicides 2006 conference.

Current HIV/AIDS statistics show that women account for almost 60% of HIV infections in Sub-Saharan Africa. HIV prevention tools such as male and female condoms, abstinence and monogamy are not always feasible options for women due to various socio-economic and cultural factors. Microbicides are products designed to be inserted in the vagina or rectum prior to sex to prevent HIV acquisition. The biannual Microbicides conference took place in Cape Town, South Africa from 23-26 April 2006. The conference was held for the first time on the African continent, the region worst affected by the HIV/AIDS pandemic. The conference brought together a record number of 1,300 scientists, researchers, policy makers, healthcare workers, communities and advocates. The conference provided an opportunity for an update on microbicide research and development as well as discussions around key issues such as ethics, acceptability, access and community involvement. This report discusses the current status of microbicide research and development, encompassing basic and clinical science, social and behavioural science, and community mobilisation and advocacy activities.

Willingness to participate in HIV vaccine efficacy trials among high risk men and women from fishing communities along Lake Victoria in Uganda.

INTRODUCTION: HIV vaccine efficacy trials conducted in suitable populations are anticipated in sub-Saharan Africa. We assessed the willingness to participate in future vaccine trials among individuals from fishing communities along Lake Victoria, Uganda. METHODS: From July to October 2012, we described a hypothetical vaccine trial to 328 (62.2% men) adults (18-49 years), at risk of HIV infection within 6 months of enrolment in a cohort and assessed their willingness to participate in the trial. Chi-square and logistic regression models were fitted to assess associations between vaccine trial attributes, participants' characteristics and willingness to participate. RESULTS: Overall, 99.4% expressed willingness to participate in the hypothetical HIV vaccine trial. This decreased marginally with introduction of particular vaccine trial attributes. Delaying pregnancy for 10 months and large blood draw had the largest effects on reducing willingness to participate to 93.5% (p=0.02) and 94.5% (p=0.01) respectively. All the vaccine trial attributes in combination reduced willingness to participate to 90.6%. This overall reduction in willingness to participate was significantly associated with gender and exchange of gifts for sex in multivariable analysis; women were more than three times as likely to have expressed unwillingness to participate in future vaccine trials as men (aOR=3.4, 95% CI: 1.55, 7.33) and participants who never received gifts in exchange for sex were more than four times as likely to have expressed unwillingness as those who received gifts for sex (aOR=4.5; 95%CI 1.30, 16.70). The main motivators of participation were access to HIV counselling and testing services (31.9%), HIV education (18.0%), hope of being prevented from acquiring HIV (16.6%) and health care (12.5%). CONCLUSION: Our study identifies an important population for inclusion in future HIV prevention trials and provides important insights into acceptability of trial procedures, differences in decisions of women and men and areas for further participant education.

Use of injectable progestin contraception and risk of STI among South African women.

OBJECTIVE: This study was conducted to determine the association between the use of injectable progestin contraception (IPC) and the risk of infection with Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), bacterial vaginosis (BV) and Trichomonas vaginalis (TV) among women in South Africa. METHODS: From August 1999 through May 2001, 643 HIV-1-negative women were recruited from family planning clinics in Orange Farm, South Africa. IPC [norethisterone enanthate (NET-EN) and depot medroxyprogesterone acetate (DMPA)] users and nonhormonal contraception users were recruited in approximately equal numbers. Eligible participants were seen at enrolment and on four follow-up visits over a 12-month period; 567 returned for at least one follow-up visit. Multivariable Poisson regression models with generalized estimating equations were used to compute the incidence rate ratios (IRRs) for infections with GC, CT, BV and TV by use of NET-EN or DMPA relative to nonuse during follow-up. RESULTS: In multivariable models, the use of DMPA slightly increased the risk of infection with CT [IRR=1.24; 95% confidence interval (95% CI)=0.80-1.94] and GC (IRR=1.30; 95% CI=0.58-2.98), although these associations were not statistically significant. In contrast, DMPA appeared to be protective for TV (IRR=0.35; 95% CI=0.12-1.01), although this estimate was very imprecise. The use of both DMPA and NET-EN was associated with a decreased risk of BV. CONCLUSIONS: The use of DMPA among women in this study population was associated with an increased - but not statistically significant - risk of cervical infection with chlamydia and gonorrhea, and a decreased risk of TV and BV. Given the inconsistencies and limitations of the data describing an increased risk of CT and GC with IPC use, the potential risk of sexually transmitted infections (STIs) must be balanced against the risk of unintended pregnancy and its health consequences, especially in developing countries. Women opting to use IPC should be counseled to use condoms to protect against STIs and HIV.

Impact of aciclovir on genital and plasma HIV-1 RNA in HSV-2/HIV-1 co-infected women: a randomized placebo-controlled trial in South Africa.

BACKGROUND: Several studies suggest that herpes simplex virus type 2 (HSV-2) may enhance HIV-1 transmission and disease progression. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of aciclovir 400 mg twice daily for 3 months in 300 HSV-2/HIV-1 co-infected women not yet on highly active antiretroviral therapy (HAART). Participants were evaluated prerandomization and at monthly visits for 3 months. Primary outcomes were the detection and quantity of genital HIV-1 RNA at the month 3 (M3) visit. Analyses were also undertaken using data from all visits. The treatment effects on plasma HIV-1 RNA, CD4 cell count and genital HSV-2 DNA were also assessed. RESULTS: At M3 fewer women had detectable genital HIV in the aciclovir group compared to placebo, but this was not significant [61/132 (46%) vs. 71/137 (52%), risk ratio (RR) 0.89, 95% confidence interval (CI) 0.70-1.14; P = 0.36]. There was also little difference in quantity of HIV-1 RNA among shedders (+0.13 log10 copies/ml, 95% CI -0.14 to 0.39) at M3. However, aciclovir significantly decreased the frequency of HIV-1 shedding over all visits [adjusted odds ratio (OR) 0.57, 95% CI 0.36-0.89]. Significant reductions in M3 plasma HIV-1 RNA (-0.34 log10 copies/ml, 95% CI 0.15-0.54), genital HSV-2 DNA (8 vs. 20%, RR 0.37, 95% CI 0.19-0.73) and genital ulceration (8 vs. 18%, RR 0.43, 95% CI 0.22-0.84) were observed in the aciclovir group. CONCLUSION: HSV-2 suppressive therapy, by reducing HIV-1 plasma viral load and altering the pattern of genital HIV-1 shedding, may contribute to the reduction in sexual transmission of HIV-1 and may delay the requirement for HAART initiation.

Improvement in healing and reduction in HIV shedding with episodic acyclovir therapy as part of syndromic management among men: a randomized, controlled trial.

BACKGROUND: It is uncertain whether episodic acyclovir will enhance ulcer healing if delivered at primary health care settings, because there is often a delay in treatment initiation. METHODS: A double-blind, randomized, placebo-controlled trial of 5-day acyclovir (400 mg 3 times daily) was conducted among men with genital ulcers in South Africa. Participants received syndromic management; were tested for ulcer etiology, human immunodeficiency virus (HIV), syphilis, and herpes simplex virus type 2 (HSV-2); and were seen over the course of a month to evaluate ulcer healing and HIV-1 RNA shedding. Outcomes were ulcer duration and HIV-1 RNA shedding, assessed on day 7 among HIV-1-seropositive participants with a herpetic ulcer. RESULTS: A total of 309 men received acyclovir, and 306 received placebo; 63% were HIV-1 positive. There were 295 HIV-1-positive participants with a herpetic ulcer. Acyclovir improved ulcer healing--61% of those receiving acyclovir healed by day 7, compared with 42% of those receiving placebo (adjusted relative risk, 1.4 [95% confidence interval, 1.1-1.8]; P= .003). Acyclovir also improved healing by a median of 3 days (P= .002) and reduced HIV-1 ulcer shedding on day 7 (24% for acyclovir vs 37% for placebo; P= .05). CONCLUSIONS: Addition of acyclovir to syndromic management will improve healing of genital ulcers and may potentially reduce HIV transmission in combination with other interventions.

Estimating the public health impact of the effect of herpes simplex virus suppressive therapy on plasma HIV-1 viral load.

OBJECTIVE: Trials of herpes simplex virus (HSV) suppressive therapy among HSV-2/HIV-1-infected individuals have reported an impact on plasma HIV-1 viral loads (PVLs). Our aim was to estimate the population-level impact of suppressive therapy on female-to-male HIV-1 sexual transmission. DESIGN AND METHODS: By comparing prerandomization and postrandomization individual-level PVL data from the first two HSV suppressive therapy randomized controlled trials in sub-Saharan Africa, we estimated the effect of treatment on duration of asymptomatic infection and number of HIV-1 transmission events for each trial. RESULTS: Assuming that a reduction in PVL is accompanied by an increased duration of HIV-1 asymptomatic infection, 4-6 years of HSV suppressive therapy produce a 1-year increase in the duration of this stage. To avert one HIV-1 transmission requires 8.8 [95% confidence interval (CI), 5.9-14.9] and 11.4 (95% CI, 7.8-27.5) women to be treated from halfway through their HIV-1 asymptomatic period, using results from Burkina Faso and South African trials, respectively. Regardless of the timing of treatment initiation, 51.6 (95% CI, 30.4-137.0) and 66.5 (95% CI, 36.7-222.6) treatment-years are required to avert one HIV-1 infection. Distributions of set-point PVL values from sub-Saharan African populations suggest that unintended adverse consequences of therapy at the population level (i.e. increased HIV-1 transmission due to increased duration of infection) are unlikely to occur in these settings. CONCLUSION: HSV suppressive therapy may avert relatively few HIV-1 transmission events per person-year of treatment. Its use as a prevention intervention may be limited; however, further research into its effect on rate of CD4 cell count decline and the impact of higher dosing schedules is warranted.

Characteristics of HIV-1 discordant couples enrolled in a trial of HSV-2 suppression to reduce HIV-1 transmission: the partners study.

BACKGROUND: The Partners HSV-2/HIV-1 Transmission Study (Partners Study) is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2) suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort. METHODS: HIV-1 serodiscordant heterosexual couples, in which the HIV-1 infected partner was HSV-2 seropositive, had a CD4 count >or=250 cells/mcL and was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern Africa. Demographic, behavioral, clinical and laboratory characteristics were assessed. RESULTS: Of the 3408 HIV-1 serodiscordant couples enrolled, 67% of the HIV-1 infected partners were women. Couples had cohabitated for a median of 5 years (range 2-9) with 28% reporting unprotected sex in the month prior to enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted infections were uncommon (<5%), except for Trichomonas vaginalis in 14% of HIV-1 infected women. Median baseline CD4 count for HIV-1 infected participants was 462cells/mcL and median HIV-1 plasma RNA was 4.2 log(10) copies/mL. After adjusting for age and African region, correlates of HIV-1 RNA level included male gender (+0.24 log(10) copies/mL; p<0.001) and CD4 count (-0.25 and -0.55 log(10) copies/mL for CD4 350-499 and >500 relative to <350, respectively, p<0.001). CONCLUSIONS: The Partners Study successfully enrolled a cohort of 3408 heterosexual HIV-1 serodiscordant couples in Africa at high risk for HIV-1 transmission. Follow-up of this cohort will evaluate the efficacy of acyclovir for HSV-2 suppression in preventing HIV-1 transmission and provide insights into biological and behavioral factors determining heterosexual HIV-1 transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT00194519.

Comparison of cervicovaginal lavage, cervicovaginal lavage enriched with cervical swab, and vaginal tampon for the detection of HIV-1 RNA and HSV-2 DNA in genital secretions.

METHODS: We compared the performance of 3 collection methods for cervicovaginal secretions [cervicovaginal lavage (CVL), CVL enriched with a cervical swab (eCVL), and vaginal tampon (VT)] to identify the most reliable method for detection of cervicovaginal HIV-1 and herpes simplex virus type 2 (HSV-2). HIV-1 RNA (Nuclisens EasyQ; BioMerieux, Marcy-l'Etoile, France), HSV-2 DNA (real-time polymerase chain reaction), and microscopic blood and semen traces were detected in samples from 19 HIV-1-HSV-2-coinfected women seen at 4 weekly visits. RESULTS: HIV-1 RNA was detected in 49 (79%) of 62 eCVLs, 41 (61%) of 67 CVLs, and 27 (57%) of 47 VTs. Detection of HIV-1 RNA was higher in eCVL compared with CVL [45/58 (78%) vs. 32/58 (55%); risk ratio 1.41, 95% confidence interval 1.05 to 1.88]. CONCLUSIONS: Although more eCVLs were contaminated with microscopic blood (29%) than CVLs (22%) or VTs (7%), detection of HIV-1 RNA remained higher using eCVL compared with CVL (risk ratio 1.43, 95% confidence interval 1.02 to 2.02) in uncontaminated samples. HSV-2 DNA was detected in less than 10% of samples by each method but in 7 (37%) of 19 women overall by 1 or more methods.

The 'healthy brothel': the context of clinical services for sex workers in Hillbrow, South Africa.

Conventional health services often present barriers to sex workers seeking health care resulting in untreated sexually transmitted infections (STI) and increased risk of HIV infection. A brothel-based clinic was established to provide STI treatment for sex workers who worked in the inner city suburb of Hillbrow, South Africa. Qualitative research demonstrated that the clinic was acceptable to women in terms of service quality, accessibility, and efficacy, and positively influenced health-seeking behaviours, health awareness, and condom use. The intervention also transformed the image of the hotels from sites of 'dirt and disease' into 'healthy brothels'. The paper concludes that clinical services offered on site are a viable alternative to the provision of conventional clinical services.

The importance of context: model projections on how microbicide impact could be affected by the underlying epidemiologic and behavioral situation in 2 African settings.

OBJECTIVE: The objective of this study was to explore how a microbicide's HIV impact is affected by behavioral and epidemiologic factors in 2 African settings: Cotonou, Benin, and Hillbrow, South Africa. METHODS: A mathematical model, fit to epidemiologic data from each setting, was used to estimate the HIV impact of introducing a microbicide with different HIV/sexually transmitted infection (STI) efficacies. Simulations were compared to explore how impact is affected by context. RESULTS: Widespread microbicide use results in a greater relative reduction in HIV incidence in Cotonou, where HIV/STIs are less prevalent. Most infections averted are from commercial sex in Cotonou but noncommercial sex in Hillbrow. The microbicide's STI efficacy is important in determining its HIV impact in both settings, but especially in Cotonou where the microbicide's HIV impact was mainly the result of its STI efficacy. CONCLUSIONS: It is important to develop and evaluate microbicides that are efficacious against STIs. However, even with the same patterns of use, a microbicide's impact and the importance of its STI efficacy will vary considerably between settings.

Are targeted HIV prevention activities cost-effective in high prevalence settings? Results from a sexually transmitted infection treatment project for sex workers in Johannesburg, South Africa.

OBJECTIVE: The objective of this study was to estimate the cost-effectiveness of syndromic management, with and without periodic presumptive treatment (PPT), in averting sexually transmitted infections (STIs) and HIV in female sex workers (FSWs) participating in a hotel-based intervention in Johannesburg. STUDY DESIGN: Financial and economic providers' costs were estimated. A mathematical model, fitted to epidemiologic data, projected the HIV and STIs averted by the intervention. Cost per HIV infection and DALY averted were estimated for different general population HIV prevalences. RESULTS: Projections suggest 53 HIV infections were averted (July 2000-June 2001) and a 3.1% decrease in the FSW HIV incidence. Cost-effectiveness was US dollars 78 per DALY averted. Incremental cost of PPT was US dollars 31 per disability-adjusted life year (DALY) averted. Initiating the intervention at 15% general HIV prevalence would have improved cost-effectiveness by 35%. Expanding PPT coverage to mass-treat all FSWs (instead of <17%) and their clients could increase impact 14-fold. CONCLUSION: The results highlight targeted interventions can be cost-effective at all stages of HIV epidemics and suggests PPT could improve the cost-effectiveness of targeted STI interventions.