Louise Knight

Effect of Herpes Simplex Suppression on Incidence of HIV among Women in Tanzania

BACKGROUND Infection with herpes simplex virus type 2 (HSV-2) is associated with an increased risk of acquiring infection with the human immunodeficiency virus (HIV). This study tested the hypothesis that HSV-2 suppressive therapy reduces the risk of HIV acquisition. METHODS Female workers at recreational facilities in northwestern Tanzania who were 16 to 35 years of age were interviewed and underwent serologic testing for HIV and HSV-2. We enrolled female workers who were HIV-seronegative and HSV-2-seropositive in a randomized, double-blind, placebo-controlled trial of suppressive treatment with acyclovir (400 mg twice daily). Participants attended mobile clinics every 3 months for a follow-up period of 12 to 30 months, depending on enrollment date. The primary outcome was the incidence of infection with HIV. We used a modified intention-to-treat analysis; data for participants who became pregnant were censored. Adherence to treatment was estimated by a tablet count at each visit. RESULTS A total of 821 participants were randomly assigned to receive acyclovir (400 participants) or placebo (421 participants); 679 (83%) completed follow-up. Mean follow-up for the acyclovir and placebo groups was 1.52 and 1.62 years, respectively. The incidence of HIV infection was 4.27 per 100 person-years (27 participants in the acyclovir group and 28 in the placebo group), and there was no overall effect of acyclovir on the incidence of HIV (rate ratio for the acyclovir group, 1.08; 95% confidence interval, 0.64 to 1.83). The estimated median adherence was 90%. Genital HSV was detected in a similar proportion of participants in the two study groups at 6, 12, and 24 months. No serious adverse events were attributable to treatment with acyclovir. CONCLUSIONS These data show no evidence that acyclovir (400 mg twice daily) as HSV suppressive therapy decreases the incidence of infection with HIV. (Current Controlled Trials number, ISRCTN35385041 [controlled-trials.com].).

Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa

Objectives:We report on outcomes after 7 years of a community-based antiretroviral therapy (ART) programme in Khayelitsha, South Africa, with death registry linkages to correct for mortality under-ascertainment. Design:This is an observational cohort study. Methods:Since inception, patient-level clinical data have been prospectively captured on-site into an electronic patient information system. Patients with available civil identification numbers who were lost to follow-up were matched with the national death registry to ascertain their vital status. Corrected mortality estimates weighted these patients to represent all patients lost to follow-up. CD4 cell count outcomes were reported conditioned on continuous virological suppression. Results:Seven thousand, three hundred and twenty-three treatment-naive adults (68% women) started ART between 2001 and 2007, with annual enrolment increasing from 80 in 2001 to 2087 in 2006. Of 9.8% of patients lost to follow-up for at least 6 months, 32.8% had died. Corrected mortality was 20.9% at 5 years (95% confidence interval 17.9–24.3). Mortality fell over time as patients accessed care earlier (median CD4 cell count at enrolment increased from 43 cells/μl in 2001 to 131 cells/μl in 2006). Patients who remained virologically suppressed continued to gain CD4 cells at 5 years (median 22 cells/μl per 6 months). By 5 years, 14.0% of patients had failed virologically and 12.2% had been switched to second-line therapy. Conclusion:At a time of considerable debate about future global funding of ART programmes in resource-poor settings, this study has demonstrated substantial and durable clinical benefits for those able to access ART throughout this period, in spite of increasing loss to follow-up.

Antiretroviral treatment outcomes from a nurse-driven, community-supported HIV/AIDS treatment programme in rural Lesotho: observational cohort assessment at two years

IntroductionLesotho has the third highest HIV prevalence in the world (an adult prevalence of 23.2%). Despite a lack of resources for health, the country has implemented state-of-the-art antiretroviral treatment guidelines, including early initiation of treatment (<350 cells/mm3), tenofovir in first line, and nurse-initiated and managed HIV care, including antiretroviral therapy (ART), at primary health care level.Programme approachWe describe two-year outcomes of a decentralized HIV/AIDS care programme run by Doctors Without Borders/Médecins Sans Frontières, the Ministry of Health and Social Welfare, and the Christian Health Association of Lesotho in Scott catchment area, a rural health zone covering 14 clinics and one district hospital. Outcome data are described through a retrospective cohort analysis of adults and children initiated on ART between 2006 and 2008.Discussion and EvaluationOverall, 13,243 people have been enrolled in HIV care (5% children), and 5376 initiated on ART (6.5% children), 80% at primary care level. Between 2006 and 2008, annual enrolment more than doubled for adults and children, with no major external increase in human resources. The proportion of adults arriving sick (CD4 <50 cells/mm3) decreased from 22.2% in 2006 to 11.9% in 2008. Twelve-month outcomes are satisfactory in terms of mortality (11% for adults; 9% for children) and loss to follow up (8.8%). At 12 months, 80% of adults and 89% of children were alive and in care, meaning they were still taking their treatment; at 24 months, 77% of adults remained in care.ConclusionDespite major resource constraints, Lesotho is comparing favourably with its better resourced neighbour, using the latest international ART recommendations. The successful two-year outcomes are further evidence that HIV/AIDS care and treatment can be provided effectively at the primary care level. The programme highlights how improving HIV care strengthened the primary health care system, and validates several critical areas for task shifting that are being considered by other countries in the region, including nurse-driven ART for adults and children, and lay counsellor-supported testing and counselling, adherence and case management.

Risk factors for herpes simplex virus type 2 and HIV among women at high risk in northwestern Tanzania - Preparing for an HSV-2 intervention trial

Objectives:To determine prevalence of and risk factors for herpes simplex virus type 2 (HSV-2) and HIV among women being screened for a randomized, controlled trial of HSV suppressive therapy in northwestern Tanzania. Methods:Two thousand seven hundred nineteen female facility workers aged 16 to 35 were interviewed and underwent serological testing for HIV and HSV-2. Factors associated with HSV-2 and HIV in women aged 16 to 24 were examined using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). Results:HSV-2 seroprevalence was 80%, and HIV seroprevalence was 30%. Among women aged 16 to 24, both infections were significantly and independently associated with older age, being a bar worker, working at a truck stop, and having more lifetime sexual partners. HSV-2 infection was also associated with lower socioeconomic status, increased alcohol intake, younger age at first sex, inconsistent condom use, and vaginal douching. There was a strong association between the 2 infections after adjustment for other factors (OR = 4.22, 95% CI: 2.6 to 6.9). Conclusions:Female facility workers in northwestern Tanzania are vulnerable to HSV-2 and HIV infections. Programs designed to increase safer sexual behavior and reduce alcohol use could be effective in reducing HSV-2 incidence and, in turn, HIV infection. This is a suitable population for an HSV suppressive therapy trial.

Microbicides Development Program, Tanzania-Baseline Characteristics of an Occupational Cohort and Reattendance at 3 Months

Objectives: To determine baseline characteristics of an occupational cohort of women in Mwanza City, Tanzania, and factors associated with reattendance at 3 months, in preparation for a microbicide trial. Study Design: One thousand five hundred seventy-three women aged 16–54 years working in food outlets and recreational facilities were enrolled, interviewed, and examined at community-based reproductive health clinics, provided specimens for HIV/STI and pregnancy testing, and attended 3 monthly clinical follow-up. Results: Baseline prevalence of HIV was 25.5%; pregnancy 9.7%; herpes simplex virus type-2 74.6%; active syphilis 10.2%, bacterial vaginosis 52.6%; gonorrhea 5.5%; chlamydia 5.9%; and trichomoniasis 12.3%. Reattendance at 3 months was 74.1% and was higher in older women, less mobile women, and in those who received an HIV-negative result at enrollment. Conclusions: Baseline characteristics of this occupational group suggest their suitability for microbicide trials. A screening round, locally appropriate informed consent procedures, and effective community tracing may help reduce losses to follow-up in such settings.

Validity of coital diaries in a feasibility study for the Microbicides Development Programme trial among women at high risk of HIV/AIDS in Mwanza, Tanzania.

Objectives: To compare coital diaries and face-to-face interviews (FFIs) in measuring sexual behaviour among women at high risk of HIV. To assess the effect of differing levels of support from researchers on reporting in coital diaries and FFIs. Methods: Three groups of 50 women were randomly selected from a cohort of food and recreational facility workers participating in a microbicide trial feasibility study and received differing levels of researcher support. Minimum support involved delivering and collecting coital diaries weekly; medium support included a weekly FFI and discussion of concerns; intensive support also included an unscheduled mid-week visit when diaries were checked and concerns addressed. All respondents participated in an exit FFI, including questions on sexual behaviour over the four-week study period and study acceptability. Results: Sexual behaviours were generally reported more frequently in coital diaries than weekly or exit interviews. Vaginal and anal sex, male and female condom use, vaginal cleaning and lubrication, sex during menstruation and sex with irregular and regular partners were reported more frequently in coital diaries than exit interviews. In coital diaries, level of support was associated with reporting of vaginal sex and cleaning. In exit interviews, support level was associated with reporting of vaginal sex, vaginal cleaning and sex with regular, irregular and commercial partners. Women with minimum support reported least satisfaction with the research process. Women with intensive support were most likely to report that they informed someone about their study participation and that they completed diaries daily. Conclusion: Compared with FFIs, coital diaries resulted in higher reporting of socially stigmatised activities, and sexual behaviour reporting varied less by level of support. More researcher support enhanced study acceptability.

Suitability of simple human immunodeficiency virus rapid tests in clinical trials in community-based clinic settings.

ABSTRACT The suitability and accuracy of using simple human immunodeficiency virus (HIV) rapid (SR) tests in community-based clinics in northwest Tanzania were determined to assess eligibility for participation in clinical trials. The HIV rapid and ELISA test results for 789 women aged 16 to 54 who were screened for two clinical trials of HIV prevention were compared. Women were offered voluntary HIV counseling and testing (VCT) at screening; those who accepted were tested with the Abbott Determine and Trinity Biotech Capillus SR tests in parallel. The results were confirmed by two parallel HIV enzyme-linked immunosorbent assay (ELISA) tests (Abbott Murex HIV Ag/Ab combination and Vironostika Uniform II HIV Ag/Ab) to determine eligibility. Positive samples for any of the four assays were confirmed by a line immunoassay and p24 testing. The parallel SR tests had high concordance (96.2%) with the parallel ELISA algorithm. The sensitivities of the SR tests were 98.6% for Capillus (95% confidence interval [CI], 95.1 to 99.8%), 99.3% for Determine (95% CI, 96.2 to 100%), and 98.6% for the parallel SR (95% CI, 95.1 to 99.8%). The specificities were 99.7% for Capillus (95% CI, 98.9 to 100%), 99.7% for Determine (95% CI, 98.9 to 100%), and 100% for the parallel SR (95% CI, 99.4 to 100%). SR tests are suitable for use in community-based clinical research settings to assess eligibility both for trial participation and for the provision of on-site VCT services.

Are Women Who Work in Bars, Guesthouses and Similar Facilities a Suitable Study Population for Vaginal Microbicide Trials in Africa?

Background A feasibility study was conducted to investigate whether an occupational at-risk cohort of women in Mwanza, Tanzania are a suitable study population for future phase III vaginal microbicide trials. Methodology/Principal Findings 1573 women aged 16–54 y working in traditional and modern bars, restaurants, hotels, guesthouses or as local food-handlers were enrolled at community-based reproductive health clinics, provided specimens for HIV/STI and pregnancy testing, and asked to attend three-monthly clinical follow-up visits for 12-months. HIV positive and negative women were eligible to enter the feasibility study and to receive free reproductive health services at any time. HIV prevalence at baseline was 26.5% (417/1573). HIV incidence among 1156 sero-negative women attending at baseline was 2.9/100PYs. Among 1020 HIV sero-negative, non-pregnant women, HIV incidence was 2.0/100PYs, HSV-2 incidence 12.7/100PYs and pregnancy rate 17.8/100PYs. Retention at three-months was 76.3% (778/1020). Among 771 HIV sero-negative, non-pregnant women attending at three-months, subsequent follow-up at 6, 9 and 12-months was 83.7%, 79.6%, and 72.1% respectively. Older women, those who had not moved home or changed their place of work in the last year, and women working in traditional bars or as local food handlers had the highest re-attendance. Conclusions/Significance Women working in food outlets and recreational facilities in Tanzania and other parts of Africa may be a suitable study population for microbicide and other HIV prevention trials. Effective locally-appropriate strategies to address high pregnancy rates and early losses to follow-up are essential to minimise risk to clinical trials in these settings.

Patterns and predictors of violence against children in Uganda: a latent class analysis

Objective To explore patterns of physical, emotional and sexual violence against Ugandan children. Design Latent class and multinomial logistic regression analysis of cross-sectional data. Setting Luwero District, Uganda. Participants In all, 3706 primary 5, 6 and 7 students attending 42 primary schools. Main outcome and measure To measure violence, we used the International Society for the Prevention of Child Abuse and Neglect Child Abuse Screening Tool—Child Institutional. We used the Strengths and Difficulties Questionnaire to assess mental health and administered reading, spelling and maths tests. Results We identified three violence classes. Class 1 (N=696 18.8%) was characterised by emotional and physical violence by parents and relatives, and sexual and emotional abuse by boyfriends, girlfriends and unrelated adults outside school. Class 2 (N=975 26.3%) was characterised by physical, emotional and sexual violence by peers (male and female students). Children in Classes 1 and 2 also had a high probability of exposure to emotional and physical violence by school staff. Class 3 (N=2035 54.9%) was characterised by physical violence by school staff and a lower probability of all other forms of violence compared to Classes 1 and 2. Children in Classes 1 and 2 were more likely to have worked for money (Class 1 Relative Risk Ratio 1.97, 95% CI 1.54 to 2.51; Class 2 1.55, 1.29 to 1.86), been absent from school in the previous week (Class 1 1.31, 1.02 to 1.67; Class 2 1.34, 1.10 to 1.63) and to have more mental health difficulties (Class 1 1.09, 1.07 to 1.11; Class 2 1.11, 1.09 to 1.13) compared to children in Class 3. Female sex (3.44, 2.48 to 4.78) and number of children sharing a sleeping area predicted being in Class 1. Conclusions Childhood violence in Uganda forms distinct patterns, clustered by perpetrator and setting. Research is needed to understand experiences of victimised children, and to develop mental health interventions for those with severe violence exposures. Trial registration number NCT01678846; Results.

Methods to increase reporting of childhood sexual abuse in surveys: the sensitivity and specificity of face-to-face interviews versus a sealed envelope method in Ugandan primary school children

BackgroundUnderreporting of childhood sexual abuse is a major barrier to obtaining reliable prevalence estimates. We tested the sensitivity and specificity of the face-to-face-interview (FTFI) method by comparing the number of disclosures of forced sex against a more confidential mode of data collection, the sealed-envelope method (SEM). We also report on characteristics of individuals associated with non-disclosure in FTFIs.MethodsSecondary analysis of data from a cross-sectional survey conducted in 2014, with n = 3843 children attending primary school in Luwero District, Uganda. Sensitivity and specificity were calculated, and mixed effects logistic regression models tested factors associated with disclosure in one or both modes.ResultsIn the FTFI, 1.1% (n = 42) of children reported ever experiencing forced sex, compared to 7.0% (n = 268) in the SEM. The FTFI method demonstrated low sensitivity (13.1%, 95%CI 9.3–17.7%) and high specificity (99.8%, 95%CI 99.6–99.9%) in detecting cases of forced sex, when compared to the SEM. Boys were less likely than girls to disclose in the FTFI, however there was no difference in prevalence by sex using the SEM (aOR = 0.91, 95%CI 0.7–1.2; P = 0.532). Disclosing experience of other forms of sexual violence was associated with experience of forced sex for both modes of disclosure.ConclusionsThe SEM method was superior to FTFIs in identifying cases of forced sex amongst primary school children, particularly for boys. Reporting of other forms of sexual violence in FTFIs may indicate experience of forced sex. Future survey research, and efforts to estimate prevalence of sexual violence, should make use of more confidential disclosure methods to detect childhood sexual abuse.