Costs and economies of scale in the accelerated program for prevention of mother-to-child transmission of HIV in Zimbabwe.

BACKGROUND: Despite a growing body of literature on HIV service costs in sub-Saharan Africa, only a few studies have estimated the facility-level cost of prevention of Mother-to-Child Transmission (PMTCT) services, and even fewer provide insights into the variation of PMTCT costs across facilities. In this study, we present the first empirical costs estimation of the accelerated program for the prevention of mother-to-child transmission of HIV in Zimbabwe and investigate the determinants of heterogeneity of the facility-level average cost per service. To understand such variation, we explored the association between average costs per service and supply-and demand-side characteristics, and quality of services. One aspect of the supply-side we explore carefully is the scale of production-which we define as the annual number of women tested or the yearly number of HIV-positive women on prophylaxis. METHODS: We collected rich data on the costs and PMTCT services provided by 157 health facilities out of 699 catchment areas in five provinces in Zimbabwe for 2013. In each health facility, we measured total costs and the number of women covered with PMTCT services and estimated the average cost per woman tested and the average cost per woman on either ARV prophylaxis or ART. We refer to these facility-level average costs per service as unitary costs. We also collected information on potential determinants of the variation of unitary costs. On the supply-side, we gathered data on the scale of production, staff composition and on the types of antenatal and family planning services provided. On the demand side, we measured the total population at the catchment area and surveyed eligible pairs of mothers and infants about previous use of HIV testing and prenatal care, and on the HIV status of both mothers and infants. We explored the determinants of unitary cost variation using a two-stage linear regression strategy. RESULTS: The average annual total cost of the PMTCT program per facility was US$16,821 (median US$8,920). The average cost per pregnant woman tested was US$80 (median US$47), and the average cost per HIV-positive pregnant woman initiated on ARV prophylaxis or treatment was US$786 annually (median US$420). We found substantial heterogeneity of unitary costs across facilities regardless of facility type. The scale of production was a strong predictor of unitary costs variation across facilities, with a negative and statistically significant correlation between the two variables (p<0.01). CONCLUSIONS: These findings are the first empirical estimations of PMTCT costs in Zimbabwe. Unitary costs were found to be heterogeneous across health facilities, with evidence consistent with economies of scale.

Discrepancies in diagnosis of incident HIV infection between antibody- and DNA-based tests in a phase III prevention trial in southern Africa.

Dried blood spots (DBS) are widely used to test for HIV in a variety of research and service delivery settings; however, uniform guidelines regarding collection, storage and DNA extraction processes have neither been developed nor evaluated. Previously published reports suggested DBS may be stored at room temperature for up to 60 days, and intensive stability tests have shown that DBS can withstand high temperatures, humidity and freeze-thawing. During the implementation of a large randomized controlled trial (RCT) in southern Africa, with HIV acquisition as the primary endpoint, we observed 65 instances when DBS samples collected from the same day as a positive HIV antibody test yielded negative DNA polymerase chain reaction (PCR) results. The source of this discrepancy may have been due to inadequate specimen volume, filter paper or DNA extraction procedures, but were most likely due to storage conditions that have been reported as acceptable in other settings.

The relative contribution of viral and bacterial sexually transmitted infections on HIV acquisition in southern African women in the Methods for Improving Reproductive Health in Africa study.

We assess the relative contribution of viral and bacterial sexually transmitted infections (STIs) on HIV acquisition among southern African women in a nested case-control study within the Methods for Improving Reproductive Health in Africa (MIRA) trial. Cases were women with incident HIV infection; controls were HIV-uninfected at the time of case seroconversion selected in a 1 to 3 case to control ratio (risk-set sampling), matched on study site and time of follow-up. Conditional logistic regression models were used to calculate adjusted odds ratios (AORs) and population-attributable fractions (PAF). Among 4948 enrolled women, we analysed 309 cases and 927 controls. The overall HIV incidence rate was 4.0 per 100 women-years. The incidence of HIV infection was markedly higher in women who had prevalent Herpes simplex virus type 2 (HSV-2) (AOR: 2.14; 95% confidence interval [CI]: 1.55-2.96), incident HSV-2 (AOR: 4.43; 95% CI: 1.77-11.05) and incident Neisseria gonorrhoeae (AOR: 6.92; 95% CI: 3.01-15.90). The adjusted PAF of HIV incidence for prevalent HSV-2 was 29.0% (95% CI: 16.8-39.3), for incident HSV-2 2.1% (95% CI: 0.6-3.6) and for incident N. gonorrhoeae 4.1% (95% CI: 2.5-5.8). Women's greatest risk factors for HIV acquisition were incident bacterial and viral STIs. Women-centred interventions aimed at decreasing HIV incidence in young African women need to address these common co-morbid conditions.

Immigration and sexual partner risk among Latino adolescents in San Francisco.

Sexual partner characteristics increase risk for adverse reproductive health outcomes. Evidence is limited regarding whether choice of sexual partners among Latino adolescents changes with U.S. acculturation/adaptation. We used generalized estimating equations to assess the associations between immigrant generation (recent immigrant, 1.5 [immigrated prior to adolescence], 2nd and 3rd) and sexual partner risk in a prospective cohort study of 411 Latino adolescents aged 14-19. We examined three measures of partner risk and mediating effects of family influence (familism and parental monitoring). The odds of reporting a partner with frequent substance use increased with increasing immigrant generation (odds ratios (OR) [reference = recent immigrants]: 2.3, 3.4, and 5.6) as did having a partner who was in a gang/incarcerated (OR [reference = recent immigrants]: 2.4, 3.6, and 5.7). Though the odds of having high-risk partners decreased with higher parental monitoring, neither family influence measure mediated these relationships. Findings underscore the need for a prevention focus on partner choice with attention to increased risk with increasing U.S. generation.

Sexual network position and risk of sexually transmitted infections.

OBJECTIVES: A population-based sexual network study was used to identify sexual network structures associated with sexually transmitted infection (STI) risk, and to evaluate the degree to which the use of network-level data furthers the understanding of STI risk. METHODS: Participants (n = 655) were from the baseline and 12-month follow-up waves of a 2001-2 population-based longitudinal study of sexual networks among urban African-American adolescents. Sexual network position was characterised as the interaction between degree (number of partners) and two-reach centrality (number of partners' partners), resulting in the following five positions: confirmed dyad, unconfirmed dyad, periphery of non-dyadic component, centre of star-like component and interior of non-star component. STI risk was measured as laboratory-confirmed infection with gonorrhoea and/or chlamydia. RESULTS: Results of logistic regression models with generalised estimating equations showed that being in the centre of a sexual network component increased the odds of infection at least sixfold compared with being in a confirmed dyad. Individuals on the periphery of non-dyadic components were nearly five times more likely to be infected than individuals in confirmed dyads, despite having only one partner. Measuring network position using only individual-based information led to twofold underestimates of the associations between STI risk and network position. CONCLUSIONS: These results demonstrate the importance of measuring sexual network structure using network data to fully capture the probability of exposure to an infected partner.

Gang exposure and pregnancy incidence among female adolescents in San Francisco: evidence for the need to integrate reproductive health with violence prevention efforts.

Among a cohort of 237 sexually active females aged 14-19 years recruited from community venues in a predominantly Latino neighborhood in San Francisco, California, the authors examined the relation between gang exposure and pregnancy incidence over 2 years of follow-up between 2001 and 2004. Using discrete-time survival analysis, they investigated whether gang membership by individuals and partners was associated with pregnancy incidence and determined whether partnership characteristics, contraceptive behaviors, and pregnancy intentions mediated the relation between gang membership and pregnancy. Pregnancy incidence was determined by urine-based testing and self-report. Latinas represented 77% of participants, with one in five born outside the United States. One quarter (27.4%) became pregnant over follow-up. Participants' gang membership had no significant effect on pregnancy incidence (hazard ratio = 1.25, 95% confidence interval: 0.54, 3.45); however, having partners who were in gangs was associated with pregnancy (hazard ratio = 1.90, 95% confidence interval: 1.09, 3.32). The male partner's perceived pregnancy intentions and having a partner in detention each mediated the effect of partner's gang membership on pregnancy risk. Increased pregnancy incidence among young women with gang-involved partners highlights the importance of integrating reproductive health prevention into programs for gang-involved youth. In addition, high pregnancy rates indicate a heightened risk for sexually transmitted infections.

A common pathway toward women's health.

This paper calls for an alternate approach to studying the aetiology of women's health conditions. Instead of the long-established disease-specific, compartmentalized approach, it recommends focusing on risk exposures that allows for the identification of multiple disease conditions that stem from the same risk factors. Identifying common risk factors and the related pathways to adverse health outcomes can lead to the development of interventions that would favourably affect more than one disease condition. The utility of such an approach is illustrated by a review of literature from across the globe on the association between gender inequity-related exposures and women's health (namely, three health conditions: sexually transmitted infections [STIs], including Human Immunodeficiency Virus [HIV], blindness, and depression; as well as two risk behaviours: eating disorders and tobacco use). The review demonstrates how women's health cannot be viewed independently from the larger social, economic, and political context in which women are situated. Promoting women's health necessitates more comprehensive approaches, such as gender-sensitization of other family members, and the development of more creative and flexible mechanisms of healthcare delivery, that acknowledge the gender inequity-related constraints that women face in their daily lives.

Effectiveness of female controlled barrier methods in preventing sexually transmitted infections and HIV: current evidence and future research directions.

OBJECTIVES: To evaluate evidence for the effectiveness of female controlled physical and chemical barrier methods in preventing STI/HIV transmission, to examine recent reviews on microbicide development, and to highlight promising research directions. To discuss challenges in conducting effectiveness research and in translating results to public health intervention. METHODS: Systematic review of articles that examined the disease prevention effectiveness of at least one female controlled barrier method. Review of conference abstracts that presented clinical and preclinical microbicide data. RESULTS: Randomised controlled trials provide evidence that female condoms confer as much protection from STIs as male condoms. Observational studies suggest that the diaphragm protects against STI pathogens. Several microbicide effectiveness studies are under way and new directions, such as adaptation of therapeutic agents as preventive products, are being examined. Substantial attention is now given to product formulation and novel delivery strategies. Combining microbicide products with different mechanisms of action as well as combining chemical and physical barriers will be necessary to maximise prevention effectiveness. CONCLUSIONS: Increased investment in the development and identification of female controlled barrier methods offers promise that additional products will be available in the years ahead. Generalizing trial results to a community setting, promoting products that may be less effective than male condoms, and bringing an effective product to scale introduce public health challenges that warrant attention. The need for female controlled barrier methods that provide women with the opportunity to take an active role in reducing their STI/HIV risk are urgently needed and constitute an essential tool to prevent continued spread of these infections.

Reliability of adolescents' self-reported sexual behavior: a comparison of two diary methodologies.

PURPOSE: To evaluate techniques for measuring high-risk sexual behaviors by comparing the reliability and acceptability of two daily sexual behavior diary modes: a written calendar and an automated telephone interview. METHODS: This randomized controlled study included 105 sexually active female adolescents aged 15-19 years recruited from among teens seeking reproductive health care services at a family planning clinic in the San Francisco Bay Area. Participants completed a standardized sexual behavior questionnaire each day for 4 weeks. Contraceptive use by method type was recorded. Reporting differences between the two diary modes were assessed using generalized estimating equations, concordance of diary and retrospective interview responses was evaluated using kappa statistics, and contingency table analysis and Poisson regression models were constructed to examine mode acceptability. RESULTS: Respondents randomized to the telephone diary cohort reported less frequent use of barrier contraceptive methods, specifically less spermicide use (odds ratio 0.27, 95% confidence interval 0.08, 0.95), and decreasing male condom use over time, whereas reports of male condom use increased for written diary respondents (p = .007). Participant characteristics associated with diary acceptability, defined as the frequency of diary completion, were assessed and teens classified as higher risk provided fewer diary reports (p < .01). Regardless of mode completed, 65% of respondents believed the telephone diary would be preferable to the written diary for most teens. CONCLUSIONS: The automated telephone diary offered an acceptable, even preferred, methodologic alternative to the written diary calendar and elicited more accurate reporting of selected contraceptive behavior.

Choice of female-controlled barrier methods among young women and their male sexual partners.

CONTEXT: Little is known about the factors associated with the choice of female-controlled, over-the-counter barrier contraceptive methods among women and their male sexual partners. METHODS: Predictors of method choice were assessed following an educational presentation on contraceptive use and risk reduction among 510 sexually active females aged 15-30 who were recruited in the San Francisco Bay Area. In addition, the primary partners of 160 of these women participated in the survey RESULTS: Twenty-two percent of women who enrolled in the study alone, 25% of those who enrolled with their main partner and 18% of these male partners chose female-controlled, over-the-counter barrier methods alone. The strongest predictor of this choice was current use of a hormonal contraceptive both for women who participated in the study on their own (odds ratio, 2.1) and for those who enrolled their partner in the study (odds ratio, 6.3). Female-controlled methods were also chosen significantly more often by teenagers than by older women; for example, among those who enrolled with a male partner, the odds ratio for selection of a female-controlled barrier method by women younger than 18 was 6.0. Among women who enrolled without a partner, those who had had multiple partners in the previous six months and those who were current users of male condoms were less likely to choose female-controlled methods (odds ratios, 0.7 and 0.5, respectively). CONCLUSIONS: Although the majority of participants did not choose female-controlled, over-the-counter barrier methods without also choosing male condoms, such female-controlled methods appear to offer an acceptable alternative for prevention of sexually transmitted infections. They may be a particularly attractive option for individuals using hormonal contraceptives and for teenage women.

HIV-specific IgG in cervicovaginal secretions of exposed HIV-uninfected female sexual partners of HIV-infected men.

The presence of human immunodeficiency virus (HIV)-specific antibodies was examined in plasma and cervicovaginal (mucosal) samples of 24 HIV-exposed uninfected (EU) female sexual partners of HIV-infected men, and compared with findings in 18 HIV-infected and 15 low-risk HIV-uninfected women. Only HIV-infected women had detectable HIV-specific immunoglobulin G (IgG) (18 of 18) or HIV-IgA (6 of 18) in cervicovaginal samples by enzyme immunoassay (EIA). However, 3 of 24 EU women had positive Western blot (WB) for HIV-IgG in cervicovaginal secretions, while 2 of 24 EU women and 1 of 15 low-risk controls had indeterminate IgG-WB. EU women with positive or indeterminate IgG-WB in the cervicovaginal samples were similar in risk to the remaining EU women. None of the HIV-uninfected women had mucosal HIV-IgA. The findings suggest that some sexually or parenterally exposed HIV-uninfected women might develop low-level mucosal IgG responses. However, it appears unlikely that HIV-specific cervicovaginal antibodies play a major role in protection from HIV infection in this EU population.

Reproductive health differences among Latin American- and US-born young women.

Investigations of reproductive health within Latinos living in the United States suggest that sexual behaviors and contraception use practices vary by ethnicity and between foreign- and US-born adolescents. This article compares high-risk sexual behaviors and reproductive health among foreign-born Latinas, US-born Latinas, and US-born non-Latinas aged 15-24 years. We recruited 361 females from reproductive health clinics in the San Francisco Bay Area of California between 1995 and 1998; these women completed an interview that assessed sexual risk behaviors and history of pregnancy, abortion, and sexually transmitted infections. Current chlamydial and gonococcal infections were detected through biological testing. Among participants aged 15-18 years, US-born Latinas were more likely to have been pregnant (odds ratio [OR] comparing US-born Latinas and US-born non-Latinas = 3.9, 95% confidence interval [CI] 1.3, 11.4), whereas among respondents aged 19-24 years, foreign-born Latinas were more likely to have been pregnant than US-born Latinas (OR = 11.3, 95% CI 1.0, 130.8) and US-born non-Latinas (OR = 64.2, 95% CI 9.9, 416.3). US-born Latinas were most likely to have had an abortion (OR comparing US-born Latinas and US-born non-Latinas = 2.0, 95% CI 0.9, 4.7). They were also most likely to have chlamydial infection at study enrollment (8.2% prevalence compared to 2.2% and 1.0%for foreign-born Latinas and US-born non-Latinas, respectively; P =.009). Reproductive health differences between foreign and US-born females and within the US-born population warrant further examination and highlight the need for targeted prevention.

Effect of intravaginal practices on the vaginal and cervical mucosa of Zimbabwean women.

OBJECTIVES: Lesions on the vaginal and cervical mucosa may facilitate transmission of HIV and other sexually transmitted diseases (STDs). We evaluated the relationship between intravaginal practices and the presence of colposcopic lesions in Zimbabwean women. METHODS: Users and nonusers of intravaginal practices were seen at enrollment, and at 1 and 6 months. Interviewing, counseling, and pelvic and colposcopic examinations were performed at each study visit. Specimens were collected at enrollment and 6 months. RESULTS: Colposcopic lesions were found at least once in 83% of the participants (n = 162), and in 66% of all exams (n = 430). Most lesions were classified as related to infection with human Papillomavirus (HPV) (58%) or another pathogen (20%), but 11% of lesions could have been caused by intravaginal practices (signal lesions). Intravaginal practices were not associated with an increased incidence in signal lesions (95 and 124 lesions per 100 person-years of follow-up for users and nonusers respectively; p = .290), nor with the presence of signal lesions in multivariate baseline (odds ratio [OR], 1.32; 95% confidence interval [CI], 0.37-4.72; p = .666) and six month transition models (OR, 1.67; 95% CI, 0.59-4.70; p = .333). CONCLUSIONS: No associations between intravaginal practices and colposcopic lesions were found in this study. However, the potential effect of intravaginal practices on the cervical and vaginal mucosa, and on subsequent HIV and STD transmission, warrants further study. The usefulness of colposcopy as a research tool in areas with high prevalences of HIV and HPV is questioned.

Intravaginal practices, vaginal flora disturbances, and acquisition of sexually transmitted diseases in Zimbabwean women.

One hundred sixty-nine Zimbabwean women were studied to determine whether the use of intravaginal practices (cleaning with the fingers, wiping the vagina, and inserting traditional substances) are associated with disturbances of vaginal flora and acquisition of sexually transmitted diseases (STDs). Subjects were interviewed and received counseling and a pelvic examination at enrollment, 1 month, and 6 months, and vaginal specimens were collected at enrollment and at 6 months. Users were more likely than nonusers to have vaginal flora disturbances but were not more likely to acquire an STD (relative risk [RR], 2.15; P=.188). Certain vaginal flora disturbances were associated with increased STD incidence and HIV prevalence. The absence of lactobacilli from the vaginal flora was associated with being positive for human immunodeficiency virus in baseline (odds ratio [OR], 0.24; P=.001) and 6-month transition multivariate models (OR, 0.39; P=.025). The presence of clue cells at baseline was associated with a higher incidence of STDs (RR, 1. 94; P=.025).

Epidemiologic evidence for time variation in HIV infectivity.

Data from three epidemiologic studies of heterosexual transmission of HIV among monogamous couples are used to assess evidence for time variation in HIV infectivity, possibly related to varying levels of infectiousness following infection in the primary infected partner. Analyses are based on statistical techniques that account for the inherent incompleteness of exposure information from such studies, and that allow direct assessment of the hypotheses that infectivity varies with time since infection and across partnerships. Data include findings from 302 couples from the California Partners' Study and 51 and 31 couples, respectively, from two U.S. Center for Disease Control and Prevention (CDC)-sponsored studies of infection in partners of transfusion recipients. Results indicate weak evidence for higher infectivity following infection of the primary partner, decreasing to relatively lower levels from 2 to 10 years after. Although these findings are consistent with biologic observations of time variation in viral levels, other explanations of the observed pattern (e.g., heterogeneity of infectivity) are equally plausible, pointing out some inherent limitations of data from such studies.

Managing HIV among serodiscordant heterosexual couples: serostatus, stigma and sex.

A qualitative study was conducted with 28 men and women in HIV-serodiscordant couples to explore the management of HIV in their relationship. Content analysis of the interviews revealed the role of serostatus and stigma in shaping partners' experience of HIV, sex and risk. Partners' differing serostatus often created feelings of alienation within the relationship. Compounding this interpersonal dynamic, the HIV service community was experienced as segregating because they were not funded or prepared to work with seronegative partners. Thus many, particularly seronegative women, felt invisible both within and outside of the relationship. Yet, the uninfected partners shared the burden of a stigmatizing illness because of the serodiscordant relationship. Stigma hindered communication about HIV and sex, disclosure to others and access to services. Many experienced HIV as a loss of their sexuality. Seronegative partners spoke about 'keeping sex alive' and often had to push to continue having sex. Couples used multiple strategies to manage HIV, including developing strict behavioural guidelines, connecting with other couples, accessing scientific information and becoming educators and activists. These altruistic activities, which also included participation in research, helped to transcend external and internalized stigma. Implications for developing interventions for HIV-serodiscordant couples are discussed.

Risk factors for plasma cell endometritis among women with cervical Neisseria gonorrhoeae, cervical Chlamydia trachomatis, or bacterial vaginosis.

OBJECTIVE: We sought to determine potential risk factors for upper genital tract inflammation in women with cervical Neisseria gonorrhoeae, Chlamydia trachomatis, or bacterial vaginosis. STUDY DESIGN: In a case-controlled study we compared 111 women with cervical Neisseria gonorrhoeae, Chlamydia trachomatis, or bacterial vaginosis (the study group) with 24 women who had negative tests for each of these infections (the control group). We evaluated potential risk factors for upper genital tract inflammation by use of bivariate and then logistic regression analysis. RESULTS: We found plasma cell endometritis in 53 of 111 women in the study group and 3 of 24 controls (odds ratio = 6.4, 95% confidence interval 1.7 to 35.0). On logistic regression, the study group women who were in the proliferative phase had increased likelihood of plasma cell endometritis (odds ratio = 4.5, 95% confidence interval 1.6 to 12.4). CONCLUSION: The proliferative phase of the menstrual cycle seems to be the primary risk factor for ascending infection by organisms associated with pelvic inflammatory disease. This may be due to a hormonal effect or to the loss of the cervical barrier during menstruation.

Genetic and immunological host factors associated with susceptibility to HIV-1 infection.

The probability of HIV transmission depends on the interplay of many different factors related to infectiousness of the HIV-infected partner, susceptibility of the HIV-uninfected partner, and biological characteristics of HIV strains. Here, we review recent studies of host immunological and genetic factors which may affect susceptibility to HIV-1 infection. These factors are summarized in Table 1. We propose how to explore biological correlates of susceptibility to HIV-1 infection in epidemiological studies, discuss the strengths and limitations of this research, and address the implications for public health.