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

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. Copyrigh

A qualitative study of participant adherence in a randomized controlled trial of herpes suppressive therapy for HIV prevention in Tanzania.

Poor participant adherence to treatment may contribute to lack of impact in some biomedical HIV prevention trials. This qualitative study explored adherence in a randomized controlled trial of herpes suppressive therapy to reduce HIV acquisition and infectivity among 1305 Tanzanian women. The trial found participants completed 72% of visits on treatment; 52-56% of women on treatment had > or = 90% adherence by pill count estimate; and between six and nine months 30/86 (35%) of urine samples from acyclovir recipients tested acyclovir negative, and 7/86 (8%) from placebo recipients tested acyclovir positive. Twenty in-depth interviews (IDIs) were conducted after 30 months with respondents randomly selected from "acyclovir negative" acyclovir recipients and "acyclovir positive" placebo recipients, or by preliminary pill count adherence categories ("under users," "good users," and "over users"). Almost all respondents reported appropriate adherence and positive trial attitudes, e.g., trusting staff, appreciating services, perceiving pills as beneficial. Fourteen understood placebo use, and six understood the trial purpose. Notably, 5/9 acyclovir recipients and 1/11 placebo recipients believed their pills had treated pre-existing sexually transmitted infections. Limited understanding did not negatively affect reported adherence. Reported adherence problems usually related to illness, travel, and/or family obligations (e.g., husband's disapproval). "Acyclovir positive" placebo recipients denied taking other participants' pills. The IDIs also did not resolve discrepant reports of pill loss or theft. Biomedical HIV interventions often have strong behavioral components that require close attention during intervention development, trial design, and process and impact evaluation. This study identified topics which warrant further consideration, including: information reinforcement and comprehension assessment throughout a trial for long-term participant understanding; involving partners in adherence promotion activities; strategizing with participants to maintain adherence during familial illnesses or other crises; and close monitoring, identification, and follow-up of (1) individuals with discrepant biological tests, and (2) other sources of the treatment in the trial area. Methodological research is also needed to improve adherence measures

Measurement and predictors of adherence in a trial of HSV suppressive therapy in Tanzania.

This study estimates adherence and identifies predictors of good adherence among 1305 Tanzanian women participating in a randomised, double-blind, placebo-controlled trial of HSV suppressive therapy to reduce HIV incidence or genital HIV shedding. Women were randomised to acyclovir 400mg BD or placebo and followed every three months for 12-30 months. Adherence was assessed by tablet counts. Random urine samples, collected between 6 and 24 months, were tested for acyclovir. At 12, 24 and 30 month visits, 56%, 52% and 54% of women on treatment had adherence >or=90%, respectively. Factors independently associated with good adherence (taking >or=90% of tablets in the preceding 3-months) included older age, understanding trial concepts at enrolment, living >2 years in the screening site, receiving an unannounced tablet check visit, using oral contraception at screening, living in the same site and house as the previous visit, accessing VCT during the trial, recent malaria and not having a positive pregnancy test. Overall, 55% of urine samples from women randomised to acyclovir had detectable acyclovir. Additional, tailored adherence strategies may be needed for younger, more mobile women and those who have not used oral contraception, which may sensitise them to daily tablet-taking. Use of biomarkers may alert investigators to adherence problems

Long-term impact of acyclovir suppressive therapy on genital and plasma HIV RNA in Tanzanian women: a randomized controlled trial.

BACKGROUND: Herpes simplex virus (HSV) suppressive therapy reduces genital and plasma human immunodeficiency virus type 1 (HIV-1) RNA over periods up to 3 months, but the long-term effect is unknown. METHODS: A total of 484 HIV-1 and HSV type 2 seropositive Tanzanian women aged 16-35 years were enrolled in a randomized placebo-controlled trial of acyclovir administered at a dosage of 400 mg twice daily. Cervico-vaginal lavage and blood samples were collected at 6 months, 12 months, and 24 months for quantification of genital and plasma HIV-1 RNA and genital HSV DNA. Primary outcomes were detection and quantity of cervico-vaginal HIV-1 RNA at 6 months. RESULTS: At 6 months, there was little difference between the acyclovir and placebo arms for cervico-vaginal HIV-1 RNA detection (88 [ 41 .3%] of 213 vs 84 [ 44 .0%] of 191; odds ratio [OR], 0.90; 95% confidence interval [CI], 0.60-1.33), HSV DNA detection (20 [ 9 .4%] of 213 vs 22 [ 11 .5%] of 191; OR, 0.80; 95% CI, 0.42-1.51), genital HIV or HSV loads, or plasma HIV-1 RNA load. Estimated median adherence was 91%. There was a suggestion of an impact on cervico-vaginal HIV-1 RNA detection among women with estimated adherence 90% (OR, 0.74; 95% CI, 0.50-1.09) when data from all 3 visits were included. CONCLUSIONS: Acyclovir administered at a dosage of 400 mg twice daily is unlikely to be a useful long-term intervention to reduce HIV transmission. The lack of effect on HIV may be attributable to suboptimal adherence or treatment regimen

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].)

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