Pregnancy incidence and correlates in a clinical trial preparedness study, North West Province South Africa.

INTRODUCTION: Women in HIV prevention trials often must typically agree to avoid pregnancy. Regardless, some become pregnant. Screening tools predicting pregnancy risk could maximize trial safety and efficiency. OBJECTIVES: We assessed incidence and correlates of pregnancy among women at high HIV risk. METHODS: We enrolled sexually-active, HIV-negative women into an observational cohort (2008-2011). At enrollment demographic, contraceptive, reproductive, pregnancy intention and behavioural data were collected. Women reported if one or both partners wanted or intended for the couple to become pregnant. We measured gender role beliefs using a locally validated eight-point index. We tested HIV and pregnancy, and inquired about sexually transmitted infection symptoms (STIs) at enrollment and monthly. HIV testing included behavioural counselling and condom provision, but did not specifically counsel women to avoid pregnancy. Cox proportional hazard modelling evaluated the associations with pregnancy. The multivariate model included the following variables "Recent pregnancy attempts", "Gender Roles Beliefs", "Self-reported STIs" and "Age". RESULTS: We screened 1068 women and excluded (24.6%, 263/1068) who did not report risk behaviour. Non-pregnant, non-sterilized women aged 18-35 (median = 21 years) enrolled (n = 438). Most women reported one partner (74.7%) and a prior live birth (84.6%). Median follow-up time was 6 months (range 0.7-15.5). Pregnancy incidence was 25.1 per 100 women-years (n = 57 pregnancies). Conservative beliefs on gender roles (Adjusted Hazard Ratio (aHR) 1.8; 95% confidence interval [CI] 1.1-2.9), recent pregnancy attempts (aHR 1.9; 95% CI 1.1-3.4) and baseline self-reported STI (aHR 2.5; 95% CI 1.4-4.4) were associated with increased incident pregnancy. Report of no pregnancy intention was associated with lowered pregnancy risk (aHR 0.3; 95% CI 0.1-0.7). CONCLUSIONS: We identified new and confirmed existing factors that can facilitate screening for pregnancy risk

Pregnancy incidence and correlates during the HVTN 503 Phambili HIV vaccine trial conducted among South African women

BACKGROUND: HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/"Phambili" vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy. METHODS: To enrol in the trial, women agreed and were supported to avoid pregnancy until 1 month after their third and final vaccination ("vaccination period"), corresponding to the first 7 months of follow-up. Unsterilized women, pooled across study arms, were analyzed. Poisson regression compared pregnancy rates during and after the vaccination period. Cox proportional hazards regression identified associations with first pregnancy. RESULTS: Among 352 women (median age 23 yrs; median follow-up 1.5 yrs), pregnancy incidence was 9.6/100 women-years overall and 6.8/100 w-yrs and 11.3/100 w-yrs during and after the vaccination period, respectively [Rate Ratio = 0.60 (0.32-1.14), p = 0.10]. In multivariable analysis, pregnancy was reduced among women who: enrolled at sites providing contraception on-site [HR = 0.43, 95% CI (0.22-0.86)]; entered the trial as injectable contraceptive users [HR = 0.37 (0.21-0.67)] or as consistent condom users (trend) [HR = 0.54 (0.28-1.04)]. Compared with women with a single partner of HIV-unknown status, pregnancy rates were increased among women with: a single partner whose status was HIV-negative [HR = 2.34(1.16-4.73)] and; 2 partners both of HIV-unknown status [HR = 4.42(1.59-12.29)]. Women with 2 more of these risk factors: marijuana use, heavy drinking, or use of either during sex, had increased pregnancy incidence [HR = 2.66 (1.24-5.72)]. CONCLUSIONS: It is possible to screen South African women for pregnancy risk at trial entry. Providing injectable contraception for free on-site and supporting consistent condom use may reduce incident pregnancy. Screening should determine the substance use, partnering, and HIV status of both members of the couple for both pregnancy and HIV prevention. Trial Registration SA National Health Research Database DOH-27-0207-1539; Clinicaltrials.gov NCT0041372

Creating an African HIV clinical research and prevention trials network: HIV prevalence, incidence and transmission

HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner

The Urban Environment and Sexual Risk Behavior among Men who have Sex with Men

Increasingly, studies show that characteristics of the urban environment influence a wide variety of health behaviors and disease outcomes, yet few studies have focused on the sexual risk behaviors of men who have sex with men (MSM). This focus is important as many gay men reside in or move to urban areas, and sexual risk behaviors and associated outcomes have increased among some urban MSM in recent years. As interventions aimed at changing individual-level risk behaviors have shown mainly short-term effects, consideration of broader environmental influences is needed. Previous efforts to assess the influence of environmental characteristics on sexual behaviors and related health outcomes among the general population have generally applied three theories as explanatory models: physical disorder, social disorganization and social norms theories. In these models, the intervening mechanisms specified to link environmental characteristics to individual-level outcomes include stress, collective efficacy, and social influence processes, respectively. Whether these models can be empirically supported in generating inferences about the sexual behavior of urban MSM is underdeveloped. Conceptualizing sexual risk among MSM to include social and physical environmental characteristics provides a basis for generating novel and holistic disease prevention and health promotion interventions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40373/2/Frye_The Urban Environment and Sexual Risk_2006.pd

Prediction of extended high viremia among newly HIV-1-infected persons in sub-Saharan Africa

Objective Prompt identification of newly HIV-infected persons, particularly those who are most at risk of extended high viremia (EHV), allows important clinical and transmission prevention benefits. We sought to determine whether EHV could be predicted during early HIV infection (EHI) from clinical, demographic, and laboratory indicators in a large HIV-1 incidence study in Africa. Design Adults acquiring HIV-1 infection were enrolled in an EHI study assessing acute retroviral syndrome (ARS) symptoms and viral dynamics. Methods Estimated date of infection (EDI) was based on a positive plasma viral load or p24 antigen test prior to seroconversion, or the mid-point between negative and positive serological tests. EHV was defined as mean untreated viral load ≥5 log10 copies/ml 130-330 days post-EDI. We used logistic regression to develop risk score algorithms for predicting EHV based on sex, age, number of ARS symptoms, and CD4 and viral load at diagnosis. Results Models based on the full set of five predictors had excellent performance both in the full population (c-statistic = 0.80) and when confined to persons with each of three HIV-1 subtypes(c-statistic = 0.80-0.83 within subtypes A, C, and D). Reduced models containing only 2-4 predictors performed similarly. In a risk score algorithm based on the final full-population model, predictor scores were one for male sex and enrollment CD4<350 cells/mm3, and two for having enrollment viral load >4.9 log10 copies/ml. With a risk score cut-point of two, this algorithm was 85% sensitive (95% CI: 76%-91%) and 61% specific (55%-68%) in predicting EHV. Conclusions Simple risk score algorithms can reliably identify persons with EHI in sub-Saharan Africa who are likely to sustain high viral loads if treatment is delayed. These algorithms may be useful for prioritizing intensified efforts around care linkage and retention, treatment initiation,adherence support, and partner services to optimize clinical and prevention outcomes

Failure of A Novel, Rapid Antigen and Antibody Combination Test to Detect Antigen-Positive HIV Infection in African Adults with Early HIV Infection

BACKGROUND: Acute HIV infection (prior to antibody seroconversion) represents a high-risk window for HIV transmission. Development of a test to detect acute infection at the point-of-care is urgent. METHODS: Volunteers enrolled in a prospective study of HIV incidence in four African cities, Kigali in Rwanda and Ndola, Kitwe and Lusaka in Zambia, were tested regularly for HIV by rapid antibody test and p24 antigen ELISA. Five subgroups of samples were also tested by the Determine Ag/Ab Combo test 1) Antigen positive, antibody negative (acute infection); 2) Antigen positive, antibody positive; 3) Antigen negative, antibody positive; 4) Antigen negative, antibody negative; and 5) Antigen false positive, antibody negative (HIV uninfected). A sixth group included serial dilutions from a p24 antigen-positive control sample. Combo test results were reported as antigen positive, antibody positive, or both. RESULTS: Of 34 group 1 samples with VL between 5x105 and >1.5x107 copies/mL (median 3.5x106), 1 (2.9%) was detected by the Combo antigen component, 7 (20.6%) others were positive by the Combo antibody component. No group 2 samples were antigen positive by the Combo test (0/18). Sensitivity of the Combo antigen test was therefore 1.9% (1/52, 95% CI 0.0, 9.9). One false positive Combo antibody result (1/30, 3.3%) was observed in group 4. No false-positive Combo antigen results were observed. The Combo antigen test was positive in group 6 at concentrations of 80 pg/mL, faintly positive at 40 and 20 pg/mL, and negative thereafter. The p24 ELISA antigen test remained positive at 5 pg/mL. CONCLUSIONS: Although the antibody component of the Combo test detected antibodies to HIV earlier than the comparison antibody tests used, less than 2% of the cases of antigen-positive HIV infection were detected by the Combo antigen component. The development of a rapid point-of-care test to diagnose acute HIV infection remains an urgent goal

Four models of HIV counseling and testing: utilization and test results in South Africa.

BACKGROUND: HIV Counseling and Testing (HCT) is the point-of-entry for pathways of HIV care and prevention. However, HCT is not reaching many who are HIV infected and this may be related to the HCT provision model. We describe HCT utilization and HIV diagnosis using four models of HCT delivery: clinic-based, urban mobile, rural mobile, and stand-alone. METHODS: Using cross-sectional data from routine HCT provided in South Africa, we described client characteristics and HIV test results from information collected during service delivery between January 2009 and June 2012. RESULTS: 118,358 clients received services at clinic-based units, 18,597; stand-alone, 28,937; urban mobile, 38,840; and rural mobile, 31,984. By unit, clients were similar in terms of median age (range 28-31), but differed in sex distribution, employment status, prior testing, and perceived HIV risk. Urban mobile units had the highest proportion of male clients (52%). Rural mobile units reached the highest proportion of clients with no prior HCT (61%) and reporting no perceived HIV risk (64%). Overall, 10,862 clients (9.3%) tested HIV-positive. CONCLUSIONS: Client characteristics varied by HCT model. Importantly, rural and urban mobile units reached more men, first-time testers, and clients who considered themselves to be at low risk for HIV

Pregnancy incidence and correlates during the HVTN 503 Phambili HIV vaccine trial conducted among South African women.

Background: HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/‘‘Phambili’’ vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy. Methods: To enrol in the trial, women agreed and were supported to avoid pregnancy until 1 month after their third and final vaccination (‘‘vaccination period’’), corresponding to the first 7 months of follow-up. Unsterilized women, pooled across study arms, were analyzed. Poisson regression compared pregnancy rates during and after the vaccination period. Cox proportional hazards regression identified associations with first pregnancy. Results: Among 352 women (median age 23 yrs; median follow-up 1.5 yrs), pregnancy incidence was 9.6/100 women-years overall and 6.8/100 w-yrs and 11.3/100 w-yrs during and after the vaccination period, respectively [Rate Ratio = 0.60 (0.32– 1.14), p = 0.10]. In multivariable analysis, pregnancy was reduced among women who: enrolled at sites providing contraception on-site [HR = 0.43, 95% CI (0.22–0.86)]; entered the trial as injectable contraceptive users [HR = 0.37 (0.21–0.67)] or as consistent condom users (trend) [HR = 0.54 (0.28–1.04)]. Compared with women with a single partner of HIV-unknown status, pregnancy rates were increased among women with: a single partner whose status was HIV-negative [HR = 2.34(1.16–4.73)] and; 2 partners both of HIV-unknown status [HR = 4.42(1.59–12.29)]. Women with 2 more of these risk factors: marijuana use, heavy drinking, or use of either during sex, had increased pregnancy incidence [HR = 2.66 (1.24–5.72)]. Conclusions: It is possible to screen South African women for pregnancy risk at trial entry. Providing injectable contraception for free on-site and supporting consistent condom use may reduce incident pregnancy. Screening should determine the substance use, partnering, and HIV status of both members of the couple for both pregnancy and HIV prevention

Pregnancy Incidence and Correlates during the HVTN 503 Phambili HIV Vaccine Trial Conducted among South African Women

HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/"Phambili" vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy.To enrol in the trial, women agreed and were supported to avoid pregnancy until 1 month after their third and final vaccination ("vaccination period"), corresponding to the first 7 months of follow-up. Unsterilized women, pooled across study arms, were analyzed. Poisson regression compared pregnancy rates during and after the vaccination period. Cox proportional hazards regression identified associations with first pregnancy.Among 352 women (median age 23 yrs; median follow-up 1.5 yrs), pregnancy incidence was 9.6/100 women-years overall and 6.8/100 w-yrs and 11.3/100 w-yrs during and after the vaccination period, respectively [Rate Ratio = 0.60 (0.32-1.14), p = 0.10]. In multivariable analysis, pregnancy was reduced among women who: enrolled at sites providing contraception on-site [HR = 0.43, 95% CI (0.22-0.86)]; entered the trial as injectable contraceptive users [HR = 0.37 (0.21-0.67)] or as consistent condom users (trend) [HR = 0.54 (0.28-1.04)]. Compared with women with a single partner of HIV-unknown status, pregnancy rates were increased among women with: a single partner whose status was HIV-negative [HR = 2.34(1.16-4.73)] and; 2 partners both of HIV-unknown status [HR = 4.42(1.59-12.29)]. Women with 2 more of these risk factors: marijuana use, heavy drinking, or use of either during sex, had increased pregnancy incidence [HR = 2.66 (1.24-5.72)].It is possible to screen South African women for pregnancy risk at trial entry. Providing injectable contraception for free on-site and supporting consistent condom use may reduce incident pregnancy. Screening should determine the substance use, partnering, and HIV status of both members of the couple for both pregnancy and HIV prevention.SA National Health Research Database DOH-27-0207-1539; Clinicaltrials.gov NCT00413725