Search

Introduction HIV‐associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in sub‐Saharan Africa (SSA). We performed a systematic review and meta‐analysis with the primary aim of estimating mortality from major causes of adult meningitis in routine care settings, and to contrast this with outcomes from clinical trial settings. Methods We searched PubMed, EMBASE and the Cochrane Library for published clinical trials (defined as randomized‐controlled trials (RCTs) or investigator‐managed prospective cohorts) and observational studies that evaluated outcomes of adult meningitis in SSA from 1 January 1990 through 15 September 2019. We performed random effects modelling to estimate pooled mortality, both in clinical trial and routine care settings. Outcomes were stratified as short‐term (in‐hospital or two weeks), medium‐term (up to 10 weeks) and long‐term (up to six months). Results and discussion Seventy‐nine studies met inclusion criteria. In routine care settings, pooled short‐term mortality from cryptococcal meningitis was 44% (95% confidence interval (95% CI):39% to 49%, 40 studies), which did not differ between amphotericin (either alone or with fluconazole) and fluconazole‐based induction regimens, and was twofold higher than pooled mortality in clinical trials using amphotericin based treatment (21% (95% CI:17% to 25%), 17 studies). Pooled short‐term mortality of TB meningitis was 46% (95% CI: 33% to 59%, 11 studies, all routine care). For pneumococcal meningitis, pooled short‐term mortality was 54% in routine care settings (95% CI:44% to 64%, nine studies), with similar mortality reported in two included randomized‐controlled trials. Few studies evaluated long‐term outcomes. Conclusions Mortality rates from HIV‐associated meningitis in SSA are very high under routine care conditions. Better strategies are needed to reduce mortality from HIV‐associated meningitis in the region.

BACKGROUND Many public health departments use record linkage between surveillance data and external data sources to inform public health interventions. However, little guidance is available to inform these activities, and many health departments rely on deterministic algorithms that may miss many true matches. In the context of public health action, these missed matches lead to missed opportunities to deliver interventions and may exacerbate existing health inequities. OBJECTIVE This study aimed to compare the performance of record linkage algorithms commonly used in public health practice. METHODS We compared five deterministic (exact, Stenger, Ocampo 1, Ocampo 2, and Bosh) and two probabilistic record linkage algorithms (fastLink and beta record linkage [BRL]) using simulations and a real-world scenario. We simulated pairs of datasets with varying numbers of errors per record and the number of matching records between the two datasets (ie, overlap). We matched the datasets using each algorithm and calculated their recall (ie, sensitivity, the proportion of true matches identified by the algorithm) and precision (ie, positive predictive value, the proportion of matches identified by the algorithm that were true matches). We estimated the average computation time by performing a match with each algorithm 20 times while varying the size of the datasets being matched. In a real-world scenario, HIV and sexually transmitted disease surveillance data from King County, Washington, were matched to identify people living with HIV who had a syphilis diagnosis in 2017. We calculated the recall and precision of each algorithm compared with a composite standard based on the agreement in matching decisions across all the algorithms and manual review. RESULTS In simulations, BRL and fastLink maintained a high recall at nearly all data quality levels, while being comparable with deterministic algorithms in terms of precision. Deterministic algorithms typically failed to identify matches in scenarios with low data quality. All the deterministic algorithms had a shorter average computation time than the probabilistic algorithms. BRL had the slowest overall computation time (14 min when both datasets contained 2000 records). In the real-world scenario, BRL had the lowest trade-off between recall (309/309, 100.0%) and precision (309/312, 99.0%). CONCLUSIONS Probabilistic record linkage algorithms maximize the number of true matches identified, reducing gaps in the coverage of interventions and maximizing the reach of public health action.

Background Tuberculosis (TB)-related stigma presents a major barrier to care of persons with TB through its impact on treatment initiation and retention in care. This is particularly challenging in settings with high prevalence of both TB and HIV where fear of HIV/AIDS can amplify stigma surrounding TB. The purpose of this study was to validate a TB stigma scale for use among persons presenting for outpatient HIV screening in the Umlazi township of South Africa and evaluate factors associated with TB-related stigma in this high HIV burden setting. Methods In this cross-sectional study, we measured TB-related stigma in adults prior to HIV testing using a 12-item scale designed to assess experienced and felt TB-related stigma. Results Among 848 adults, mean age was 32 years, 54% were male, and the median TB stigma score was 19 of 36 (interquartile range 15–23). We identified two factors in the stigma scale which had excellent reliability (Cronbach’s alpha 0.85, 0.89). Persons with high TB stigma were more likely to be male (adjusted relative risk ratio [aRRR] 1.56, 95% confidence interval [CI] 1.11–2.28) and have accurate knowledge of TB transmission (aRRR 1.90, 95% CI 1.16–3.10) as compared to those with low stigma. Variables not significantly associated with stigma in the multivariate model included education, income, prior TB or HIV diagnoses, and depression. Conclusions Male sex and TB knowledge were associated with higher TB stigma in an outpatient HIV clinic in a South African township. Identifying risk factors associated with stigma will be important to guide stigma reduction interventions.

SafeBoda is a transportation company that provides road safety training and helmets to its motorcycle taxi drivers in Kampala. We sought to determine whether risk of road traffic crash (RTC) was lower in SafeBoda compared to regular (non-SafeBoda) motorcycle taxi drivers during a 6-month follow-up period. We collected participant demographic and behavioural data at baseline using computer-assisted personal interview, and occurrence of RTC every 2 months using text messaging and telephone interview from a cohort of 342 drivers. There were 85 crashes (31 in SafeBoda and 54 in regular drivers) during follow-up. Over the 6-month follow-up period, SafeBoda drivers were 39% less likely to be involved in a RTC than regular drivers after adjusting for age, possession of a driver’s license, and education (RR: 0.61, 95% CI: 0.39–0.97, p = .04). These findings suggest that the SafeBoda programme results in safer driving and fewer RTCs among motorcycle taxi drivers in Kampala.

Women at high risk of HIV infection, including sex workers and those with active genital inflammation, have molecular signatures of immune activation and epithelial barrier remodeling in samples of their genital mucosa. These alterations in the local immunological milieu are likely to impact HIV susceptibility. We here analyze host genital protein signatures in HIV uninfected women, with high frequency of condom use, living in HIV-serodiscordant relationships. Cervicovaginal secretions from women living in HIV-serodiscordant relationships (n = 62) were collected at three time points over 12 months. Women living in HIV-negative seroconcordant relationships (controls, n = 25) were sampled at one time point. All study subjects were examined for demographic parameters associated with susceptibility to HIV infection. The cervicovaginal samples were analyzed using a high-throughput bead-based affinity assay. Proteins involved in epithelial barrier function and inflammation were increased in HIV-serodiscordant women. By combining several methods of analysis, a total of five proteins (CAPG, KLK10, SPRR3, elafin/PI3, CSTB) were consistently associated with this study group. Proteins analyzed using the affinity set-up were further validated by label-free tandem mass spectrometry in a partially overlapping cohort with concordant results. Women living in HIV-serodiscordant relationships thus had elevated levels of proteins involved in epithelial barrier function and inflammation despite low prevalence of sexually transmitted infections and a high frequency of safe sex practices. The identified proteins are important markers to follow during assessment of mucosal HIV susceptibility factors and a high-throughput bead-based affinity set-up could be a suitable method for such evaluation.

Introduction Spontaneous interferon‐γ (IFNγ) released detected by enzyme‐linked immunospot (ELISpot) assays may be a biological phenomenon. Markers of immune activation levels were assessed as correlates of high background among individuals in Kenya. Methods Couples concordantly seronegative for HIV‐1 were enrolled. IFN‐γ ELISpot assays were conducted and negative control wells were categorized as having either high or low background (≥50 and

Background World Health Organization (WHO) guidelines recommend dual contraceptive method use with condoms and another contraceptive to reduce both incidence of HIV/sexually transmitted infection transmission and unintended pregnancies. This qualitative study assessed the barriers to and motivations for dual contraceptive use in Kenyan HIV-serodiscordant couples. Methods HIV-serodiscordant couples in Nairobi, Kenya, were recruited from two longitudinal cohorts. Qualitative semistructured interviews were conducted using a semistructured questionnaire. Twelve male and 12 female members of serodiscordant couples and 10 women with incident pregnancies during the cohort studies were included. Results Few couples reported using dual contraceptive methods, with men reporting more condom use than women. No HIV-seropositive men or HIV-seronegative women reported using non-condom contraception. Men and women agreed that men play a dominant role in decisions to use both condoms and contraception in HIV-serodiscordant couples. Participants reported that perceptions of side effects, male partner preference, and reproductive desire were critical factors in contraceptive decisions. Both men and women saw dual contraceptive method use as redundant and a sign of possible unfaithfulness. Many participants actively desired pregnancy, but few were able to accurately define monthly fertility windows. Conclusions Dual contraceptive method use was low in these HIV-serodiscordant couples, with some couples finding it unnecessary while using condoms, and others being more focused on conceiving a child. Biomedical HIV prevention, including male circumcision, pre-exposure prophylaxis or antiretroviral therapy to reduce HIV transmission, may be more acceptable strategies to promote safer sexual relations among HIV-serodiscordant couples and safer conception when desired.

ObjectiveThe effects of sex hormones on the immune defenses of the female genital mucosa and its susceptibility to infections are poorly understood. The injectable hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may increase the risk for HIV-1 acquisition. We assessed the local concentration in the female genital mucosa of cationic polypeptides with reported antiviral activity in relation to DMPA use.MethodsHIV-1-uninfected women were recruited from among couples testing for HIV in Nairobi, Kenya. Cervicovaginal secretion samples were collected, and the concentrations of HNP1-3, LL-37, lactoferrin, HBD-2, and SLPI were measured by enzyme-linked immunosorbent assays. Levels of cationic polypeptides in cervicovaginal secretions were compared between women who were not using hormonal contraception and those using DMPA, oral, or implantable contraception.ResultsAmong 228 women, 165 (72%) reported not using hormonal contraception at enrollment, 41 (18%) used DMPA, 16 (7%) used an oral contraceptive, and 6 (3%) used a contraceptive implant. Compared with nonusers of hormonal contraception, DMPA users had significantly higher mean levels of HNP1-3 (2.38 vs. 2.04 log₁₀ ng/mL; P = 0.024), LL-37 (0.81 vs. 0.40 log10 ng/mL; P = 0.027), and lactoferrin (3.03 vs. 2.60 log₁₀ ng/mL; P = 0.002), whereas SLPI and HBD-2 were similar.ConclusionsAlthough all analyzed cationic polypeptides have intrinsic antiviral capacity, their interaction and cumulative effect on female genital mucosa susceptibility to infections in vivo has yet to be unraveled. This study suggests a potential mechanism underlying the effect of DMPA on the innate immune defenses, providing a rationale to investigate its effect on HIV-1 acquisition risk.

Individual and sexual partner characteristics may increase the risk of abnormal cervical cytology among women in human immunodeficiency virus (HIV)-discordant relationships. Papanicolaou smears were obtained in a prospective cohort of Kenyan HIV-discordant couples. Of 441 women, 283 (64%) were HIV-infected and 158 (36%) were HIV-uninfected with HIV-infected partners. Overall, 79 (18%) had low-grade and 25 (6%) high-grade cervical abnormalities. Male herpes simplex virus type 2 (HSV-2) seropositivity and lower couple socioeconomic status were associated with cervical abnormalities ( p 350 cells/µL) had the lowest prevalence of high-grade cervical lesions. HIV-infected women (CD4 > 350 cells/µL) and HIV-uninfected women with HIV-infected partners (CD4 ≤ 350 cells/µL) were at similar intermediate risk ( p > 0.05), and HIV-infected women (CD4 ≤ 350 cells/µL) had significantly higher risk of high-grade cervical abnormalities ( p = 0.05). Women in HIV-discordant relationships have high rates of cervical lesions and this may be influenced by couple-level factors, including HIV status and CD4 count of the infected partner.

Herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcer disease in the world, and sub-Saharan Africa bears a heavy burden of infections [1, 2]. Manifestations of HSV-2 infection range from asymptomatic or nonulcerative symptoms to periodic outbreaks of painful ulcers [3, 4]. There is a strong synergistic relationship between HSV-2 and human immunodeficiency virus type 1 (HIV-1), resulting in greater shedding and elevated infectiousness of both viruses [5–10]. HSV-2 can be managed with episodic antiviral medication (eg, acyclovir, valacyclovir, or famciclovir) to abort or reduce the duration of outbreaks or with daily suppressive treatment to prevent outbreaks and reduce asymptomatic viral shedding [11]. Although suppressive HSV-2 treatment reduces plasma HIV-1 viral load, a recent randomized trial failed to show a benefit of suppressive acyclovir therapy in reducing HIV-1 transmission [12]. However, daily suppressive therapy with valacyclovir decreases herpes transmission to sexual partners [13]. Prevention of new HSV-2 infections may be an effective HIV-1 prevention strategy, particularly among HIV-1-discordant couples in which either member of the couple is HSV-2 seronegative. While estimates vary due to population characteristics, 10%–25% of new HIV-1 infections in sub-Saharan Africa occur in HIV-1-discordant couples [14–17]. In this region, HSV-2 prevalence in one or both members of HIV-1-discordant couples is as high as 80% [18]. Yet there is limited knowledge about the timing and risk factors for HSV-2 acquisition in this high-risk population. Given the importance of HSV-2 in mediating HIV-1 transmission, we sought to better understand HSV-2 transmission in HIV-1-discordant couples by investigating its prevalence and incidence among stable HIV-1-discordant heterosexual couples in Nairobi, Kenya.

HIV-1 serodiscordant couples may experience increased risks of relationship dissolution; however, longitudinal stability of these relationships is poorly understood. We determined rates and correlates of separation among 469 serodiscordant couples in Nairobi and found that 113 (24 %) separated during 2 years of follow-up. Couples with a female HIV-1 infected partner (F+M–) and no income were more likely to separate than M+F– couples without income (HR = 5.0; 95 % CI 1.1–25.0), and F+M– and M+F– couples with income (HR = 2.4; 95 % CI 1.3–4.5 and HR = 2.3; 95 % CI 1.2–4.8, respectively). High separation rates may be important for couple support services and for conducting discordant couple studies.

A number of studies of highly exposed HIV-1-seronegative individuals (HESN) have found HIV-1-specific cellular responses. However, there is limited evidence that responses prevent infection or are linked to HIV-1 exposure. Peripheral blood mononuclear cells (PBMC) were isolated from HESN in HIV-1-discordant relationships and low-risk controls in Nairobi, Kenya. HIV-1-specific responses were detected using gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assays stimulated by peptide pools spanning the subtype A HIV-1 genome. The HIV-1 incidence in this HESN cohort was 1.5 per 100 person years. Positive ELISpot responses were found in 34 (10%) of 331 HESN and 14 (13%) of 107 low-risk controls (odds ratio [OR] = 0.76;P= 0.476). The median immunodominant response was 18.9 spot-forming units (SFU)/106peripheral blood mononuclear cells (PBMC). Among HESN, increasing age (OR = 1.24 per 5 years;P= 0.026) and longer cohabitation with the HIV-1-infected partner (OR = 5.88 per 5 years;P= 0.003) were associated with responses. These factors were not associated with responses in controls. Other exposure indicators, including the partner's HIV-1 load (OR = 0.99 per log10copy/ml;P= 0.974) and CD4 count (OR = 1.09 per 100 cells/μl;P= 0.238), were not associated with responses in HESN. HIV-1-specific cellular responses may be less relevant to resistance to infection among HESN who are using risk reduction strategies that decrease their direct viral exposure.

BACKGROUND: In Kenya and much of sub-Saharan Africa nearly half of all couples affected by HIV are discordant. Antiretroviral therapy (ART) slows disease progression in HIV-1-infected individuals and reduces transmission to uninfected partners. We examined time to ART initiation and factors associated with delayed initiation in HIV-1-discordant couples in Nairobi. METHODS: HIV-1-discordant couples were enrolled and followed quarterly for up to 2 years. Clinical staff administered questionnaires and conducted viral loads and CD4 counts. Participants with a CD4 count meeting ART criteria were referred to a nearby US Presidents Emergency Plan for AIDS Relief-funded treatment center. Barriers to ART initiation among participants with a CD4 count eligible for ART were assessed by Cox regression. RESULTS: Of 439 HIV-1-infected participants (63.6% females and 36.4% males) 146 met CD4 count criteria for ART during follow-up. Median time from meeting CD4 criteria until ART initiation was 8.9 months with 42.0% of eligible participants on ART by 6 months and 63.4% on ART by 1 year. The CD4 count at the time of eligibility was inversely associated with time to ART initiation (hazard ratio = 0.49 P < 0.001). Compared with homeowners those paying higher rents started ART 48% more slowly (P = 0.062) and those paying lower rents started 71% more slowly (P = 0.002). CONCLUSIONS: Despite access to regular health care referrals to treatment centers and free access to ART over one-third of participants with an eligible CD4 count had not started ART within 1 year. Factors of lower socioeconomic status may slow ART initiation and targeted approaches are needed to avoid delays in treatment initiation.

BackgroundHIV-1-discordant couples that remain discordant despite repeated exposure may differ from the general population in their distribution of transmission risk factors, including low plasma viral load (PVL) in the infected partner even in the absence of antiretroviral therapy (ART).MethodsWe followed two cohorts of HIV-1-infected Kenyan women: females in discordant couples (FDC) and female sex workers (FSW). We compared the distribution of undetectable (ResultsWe evaluated 296 FDC and 220 FSW. At baseline, FDC were more likely to have undetectable (RR = 6.94, bootstrap 95% CI: 3.47, 20.81) and low PVL (RR = 3.53, bootstrap 95% CI: 2.57, 5.65) than FSW. Similarly, both repeat undetectable PVL (RR = 9.36, bootstrap 95% CI: 6.04, 10.97) and repeat low (RR = 4.99, bootstrap 95% CI: 2.33, 14.04) PVL were more likely among FDC than FSW during follow-up.DiscussionWe observed higher prevalence of viral control in FDC compared to FSW in the absence of ART, suggesting potentially higher prevalence of biological HIV resistance factors among discordant couples.

Breastmilk chemokines have been associated with increased HIV-1 RNA levels in breastmilk and altered risk of mother-to-child HIV-1 transmission. To characterize CC and CXC chemokines in breastmilk postpartum, we collected breastmilk specimens at regular intervals for 6 months after delivery from women with and without HIV-1 infection and used commercial ELISA kits to measure breastmilk concentrations of MIP-1alpha, MIP-1beta, RANTES, and SDF-1alpha. Among 54 HIV-1-infected and 26 uninfected women, mean chemokine levels were compared cross-sectionally and longitudinally at days 5 and 10, and months 1 and 3 postpartum. For both HIV-1-infected and uninfected women, breastmilk chemokine levels were highest at day 5 for MIP-1alpha, MIP-1beta, and SDF-1alpha, and subsequently decreased. RANTES levels remained constant over the follow-up period among HIV-1-uninfected women, and increased moderately among HIV-1-infected women. For MIP-1beta and RANTES, breastmilk levels were significantly higher among HIV-1-infected women compared to uninfected women early postpartum. In addition, HIV-1-infected women transmitting HIV-1 to their infant had consistently higher breastmilk RANTES levels than those who did not transmit, with the greatest difference observed at 1 month (2.68 vs. 2.21 log10 pg/mL, respectively; p = 0.007). In summary, all four chemokines were most elevated within the first month postpartum, a period of high transmission risk via breastmilk. MIP-1beta and RANTES levels in breastmilk were higher among HIV-1-infected women than among uninfected women, and breastmilk RANTES was positively associated with vertical transmission in this study, consistent with results from our earlier cohort.

Despite the widespread availability of oral rehydration therapy, diarrheal illness remains a major cause of morbidity and mortality around the world. Previous studies have shown individualized homeopathic therapy to be effective in treating childhood diarrhea, but this approach requires specialized training.A homeopathic combination medicine, if effective, could be used by health personnel on a widespread basis.A double-blind randomized controlled trial was conducted in Honduras to evaluate the effectiveness of a homeopathic combination therapy to treat acute diarrhea in children. A total of 292 children with acute diarrhea was recruited; 145 were randomized to the experimental group and 147 to the placebo group. Tablets containing a combined preparation of the five most common single homeopathic remedies used to treat diarrhea or placebo were administered by a parent after each unformed stool. Children were followed up daily for 7 days or until symptoms resolved, whichever occurred first. Time until resolution of symptoms, daily rate of unformed stools, and total number of unformed stools were compared between the two groups.There was no significant difference in the likelihood of resolution of diarrheal symptoms between the treatment and placebo groups (hazard ratio = 1.02, 95% confidence interval: 0.79-1.32), with a median time until resolution of 3 days for both groups. Children in the treatment group had an average of 2.6 unformed stools per day compared to 2.8 among those in the placebo group; this difference was not significant (p = 0.43). The median number of unformed stools was 7 among children in the treatment group and 8 among those in the placebo group (p = 0.41).The homeopathic combination therapy tested in this study did not significantly reduce the duration or severity of acute diarrhea in Honduran children. Further study is needed to develop affordable and effective methods of using homeopathy to reduce the global burden of childhood diarrhea.

The major histocompatibility complex (MHC) is comprised of the class I, class II, and class III regions, including the MHC class I and class II genes that play a primary role in the immune response and serve as an important model in studies of primate evolution. Although nonhuman primates contribute significantly to comparative human studies, relatively little is known about the genetic diversity and genomics underlying nonhuman primate immunity. To address this issue, we sequenced a complete rhesus macaque MHC spanning over 5.3 Mb, and obtained an additional 2.3 Mb from a second haplotype, including class II and portions of class I and class III. A major expansion of from six class I genes in humans to as many as 22 active MHC class I genes in rhesus and levels of sequence divergence some 10-fold higher than a similar human comparison were found, averaging from 2% to 6% throughout extended portions of class I and class II. These data pose new interpretations of the evolutionary constraints operating between MHC diversity and T-cell selection by contrasting with models predicting an optimal number of antigen presenting genes. For the clinical model, these data and derivative genetic tools can be implemented in ongoing genetic and disease studies that involve the rhesus macaque.

BACKGROUND: Increasing evidence suggests that depot medroxyprogesterone acetate (DMPA) and intravaginal practices may be associated with an increased risk of HIV infection; however the mechanisms are not fully understood. This study evaluated the effect of DMPA and intravaginal practices on the genital mucosal proteome and microbiome to gain mechanistic insights. METHODS: Cervicovaginal secretions from 86 Kenyan women including self-reported DMPA (n=23) and non-hormonal contraceptive users (n=63) and women who practice vaginal drying (n=46) were analyzed using tandem-mass spectrometry in a cross sectional manner. RESULTS: We identified 473 human and 486 bacterial proteins from 18 different genera. DMPA use associated with increased hemoglobin and immune activation (HBD HBB ALAD IL36G) and decreased epithelial repair proteins (TFF3 F11R). Vaginal drying associated with increased hemoglobin and decreased phagocytosis factors (AZU1 MYH9 PLAUR PADI4). Injury signatures were exacerbated in DMPA users who also practiced vaginal drying. Vaginal drying associated with more diverse (H-index: 0.71 vs 0.45 p=0.0089) bacterial communities containing Gardnerella vaginalis whereas DMPA showed no significant changes in community composition or diversity. CONCLUSIONS: These findings provide new insights into the impact of DMPA and vaginal drying on mucosal barriers and future investigations are needed to confirm their relationship with HIV risk in women. (c) The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

OBJECTIVE Cervicovaginal HIV-1-neutralizing immunoglobulin A (IgA) was associated with reduced HIV-1 acquisition in a cohort of commercial sex workers. We aimed to define the prevalence and correlates of HIV-1-neutralizing IgA from HIV-1-exposed seronegative (HESN) women in HIV-1-serodiscordant relationships. METHODS HIV-1-serodiscordant couples in Nairobi were enrolled and followed quarterly up to 2 years, and women in concordant HIV-1-negative relationships were enrolled as controls. Cervicovaginal, seminal, and blood samples were collected at enrollment and follow-up. Cervicovaginal IgA was assessed for HIV-1-neutralizing activity by a peripheral blood mononuclear cell-based assay using an HIV-1 clade A primary isolate. RESULTS HESN women in discordant relationships had significantly more HIV-1-neutralizing IgA detected in genital secretions compared with control women [36 of 155 (23%) vs. four of 70 (6%), respectively; odds ratio (OR) 5.0; 95% confidence interval (CI) 1.70-14.64; P = 0.003]. These responses persisted over time in all available follow-up cervicovaginal samples from women with detectable HIV-1-neutralizing IgA at baseline. Partner median HIV-1 plasma viral load was lower among women who had HIV-1-neutralizing IgA compared with women without detectable activity (4.3 vs. 4.8 log(10) copies/ml, respectively; OR 0.70; 95% CI 0.51-0.94; P = 0.02). A similar trend was found with partner seminal viral load (OR 0.57; 95% CI 0.32-1.02; P = 0.06). CONCLUSION HESN women were five times more likely to have neutralizing IgA in cervicovaginal secretions than low-risk control women, and these responses were inversely associated with partner viral load. These observations support the existence of antiviral activity in the mucosal IgA fraction following sexual HIV-1 exposure.

Timely initiation of antiretroviral therapy (ART) is particularly important for HIV-discordant couples because viral suppression greatly reduces the risk of transmission to the uninfected partner. To identify issues and concerns related to ART initiation among HIV-discordant couples, we recruited a subset of discordant couples participating in a longitudinal study in Nairobi to participate in in-depth interviews and focus group discussions about ART. Our results suggest that partners in HIV-discordant relationships discuss starting ART, yet most are not aware that ART can decrease the risk of HIV transmission. Additionally, their concerns about ART initiation include side effects, sustaining an appropriate level of drug treatment, HIV/AIDS related stigma, medical/biological issues, psychological barriers, misconceptions about the medications, the inconvenience of being on therapy, and lack of social support. Understanding and addressing these barriers to ART initiation among discordant couples is critical to advancing the HIV “treatment as prevention” agenda.

Background Longitudinal studies of HIV-1-infected individuals or those at risk of infection are subject to missed study visits that may have negative consequences on the care of participants and can jeopardize study validity due to bias and loss of statistical power. Distance between participant residence and study clinic, as well as other socioeconomic and demographic factors, may contribute to interruptions in patient follow-up. Methods HIV-1-serodiscordant couples were enrolled between May 2007 and October 2009 and followed for two years in Nairobi, Kenya. At baseline, demographic and home location information was collected and linear distance from each participant’s home to the study clinic was determined. Participants were asked to return to the study clinic for quarterly visits, with follow-up interruptions (FUI) defined as missing two consecutive visits. Cox proportional hazards regression was used to assess crude and adjusted associations between FUI and home-to-clinic distance, and other baseline characteristics. Results Of 469 enrolled couples, 64% had a female HIV-1-infected partner. Overall incidence of FUI was 13.4 per 100 person-years (PY), with lower incidence of FUI in HIV-1-infected (10.8 per 100 PY) versus -uninfected individuals (16.1 per 100 PY) (hazard ratio [HR] = 0.66; 95% confidence interval [CI]: 0.50, 0.88). Among HIV-1-infected participants, those living between 5 and 10 kilometers (km) from the study clinic had a two-fold increased rate of FUI compared to those living

Objectives Our study aimed to assess adult women’s knowledge of human papillomavirus (HPV) and cervical cancer, and characterize their attitudes towards potential screening and prevention strategies. Methods Women were participants of an HIV-discordant couples cohort in Nairobi, Kenya. An interviewer-administered questionnaire was used to obtain information on sociodemographic status, and sexual and medical history at baseline and on knowledge and attitudes towards Pap smears, self-sampling, and HPV vaccination at study exit. Results Only 14% of the 409 women (67% HIV-positive; median age 29 years) had ever had a Pap smear prior to study enrollment and very few women had ever heard of HPV (18%). Although most women knew that Pap smears detect cervical cancer (69%), very few knew that routine Pap screening is the main way to prevent ICC (18%). Most women reported a high level of cultural acceptability for Pap smear screening and a low level of physical discomfort during Pap smear collection. In addition, over 80% of women reported that they would feel comfortable using a self-sampling device (82%) and would prefer at-home sample collection (84%). Nearly all women (94%) reported willingness to be vaccinated to prevent cervical cancer if offered at no or low cost. Conclusions These findings highlight the need to educate women on routine use of Pap smears in the prevention of cervical cancer and demonstrate that vaccination and self-sampling would be acceptable modalities for cervical cancer prevention and screening.

Background HIV exposed seronegative (HESN) women represent the population most in need of a prophylactic antiviral strategy. Mucosal cationic polypeptides can potentially be regulated for this purpose and we here aimed to determine their endogenous expression and HIV neutralizing activity in genital secretions of women at risk of HIV infection. Methodology/Principal Findings Cervicovaginal secretions (CVS) of Kenyan women in HIV-serodiscordant relationships (HESN, n = 164; HIV seropositive, n = 60) and low-risk controls (n = 72) were assessed for the cationic polypeptides HNP1–3, LL-37 and SLPI by ELISA and for HIV neutralizing activity by a PBMC-based assay using an HIV primary isolate. Median levels of HNP1–3 and LL-37 in CVS were similar across study groups. Neither HSV-2 serostatus, nor presence of bacterial vaginosis, correlated with levels of HNP1–3 or LL-37 in the HESN women. However, an association with their partner's viral load was observed. High viral load (>10,000 HIV RNA copies/ml plasma) correlated with higher levels of HNP1–3 and LL-37 (p = 0.04 and 0.03, respectively). SLPI was most abundant in the low-risk group and did not correlate with male partner's viral load in the HESN women. HIV neutralizing activity was found in CVS of all study groups. In experimental studies, selective depletion of cationic polypeptides from CVS rendered the remaining CVS fraction non-neutralizing, whereas the cationic polypeptide fraction retained the activity. Furthermore, recombinant HNP1–3 and LL-37 could induce neutralizing activity when added to CVS lacking intrinsic activity. Conclusions/Significance These findings show that CVS from HESN, low-risk, and HIV seropositive women contain HIV neutralizing activity. Although several innate immune proteins, including HNP1–3 and LL-37, contribute to this activity these molecules can also have inflammatory properties. This balance is influenced by hormonal and environmental factors and in the present HIV serodiscordant couple cohort study we show that a partner's viral load is associated with levels of such molecules.

This study examines the incidence and predictors of pregnancy in HIV-1-discordant couples from Nairobi, Kenya. Women from 454 discordant couples were followed for up to 2 years. One-year cumulative incidence of pregnancy was 9.7%. Pregnancy rates did not differ significantly between HIV-1-infected and uninfected women (HR = 1.46). The majority of pregnancies occurred among women < 30 years old reporting a desire for future children (1-year incidence 22.2%). Pregnancy rates may be high among discordant couples, indicating desire for children may override concerns of HIV-1 transmission and increase unprotected sex, and highlighting the need to make conception safer.

To evaluate the effectiveness of "First Steps", Washington State's expanded Medicaid prenatal and post-partum care program, we conducted a retrospective population-based cohort study using birth and hospital discharge records from Washington State for 1999-2002.Birth outcomes of 19,668 First Steps participants receiving Medicaid were compared to those of 56,728 non-participating mothers receiving Medicaid. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the association between First Steps participation and low birth weight (2500g), preterm birth (37 weeks gestation), small for gestational age (10th percentile in birth weight for Washington State infants of same gestational age and sex), and infant mortality (death prior to 12 months).Adjusted for potential confounders of maternal age, race/ethnicity, education, marital status, parity, place of residence, foreign birth, and participation in other benefit programs, infants of women participating in First Steps were less likely to be of low birth weight (OR=0.92, 95% CI: 0.84-1.00). Among Hispanic women, compared to non-participants, participants had a reduced odds of low birth weight (OR=0.79, 95% CI: 0.67-0.94) and preterm birth (OR=0.85, 95% CI: 0.74-0.98).These results suggest that participation in First Steps among Medicaid recipients may be particularly effective among Hispanic mothers.

In sub-Saharan Africa, approximately 1 in 2 HIV-1-infected persons living in a couple have a serodiscordant partner. Recent data suggest a large proportion of new HIV-1 infections in mature epidemics occur within discordant couples, making discordancy a major contributor to the spread of HIV/AIDS in Africa. What accounts for high rates of HIV-1 discordance and why some individuals remain uninfected despite repeated sexual exposure to HIV-1 is unknown. Studying HIV-1-discordant couples may contribute to understanding correlates of HIV-1 immunity and acute infection. Additionally, HIV-1-discordant couples are an important population for prevention efforts. Consequently, HIV-1-discordant couples are increasingly viewed as a valuable source of participants for HIV vaccine and prevention trials. This review summarizes and critiques existing data on HIV-1-discordant couples in developing countries, including an analysis of transmission rates within discordant couples, description of biological and behavioral characteristics important in planning HIV-1 vaccine and prevention trials, and challenges faced when carrying out such studies.

Background To describe HSV-2 prevalence, incidence and their correlates among stable HIV-1 discordant heterosexual couples enrolled in an HIV-1 prevention cohort study in Nairobi, Kenya. Methods Between 2007 and 2009, 469 HIV-1 discordant couples were recruited from VCT centers, and were followed up quarterly for up to 2 years. Clinical staff administered a questionnaire assessing socio-demographics, behaviour, and biological characteristics. HSV-2 status was assessed using Focus Herpe-Select2 HSV IgG ELISA. Correlates of HSV-2 infection at enrolment, and during follow-up were identified by logistic regression and Cox proportional hazards analysis respectively. Results Of the couples, 189 (40%) were HSV-2 concordant positive, 114 (24%) were HSV-2 discordant, and 85 (18%) were concordant negative. The incidence of HSV-2 infection was 8.7 cases/100 person-years. 19 (17%) individuals in an initially HSV-2 discordant partnership and 11 (13%) in an initially HSV-2 concordant negative partnership acquired HSV-2 during follow-up. Of these 11 individuals, 9(81%) were the HIV-1 positive index case in the HIV-1 discordant relationship. In a multivariate analysis, HSV-2 prevalence at baseline was significantly associated with female gender (OR 4.4; (95% CI 2.9 to 6.7)), having an HSV-2 positive partner (OR 7.6; (95% CI 5.1 to 11.2)), being HIV positive (OR 2.2; (95% CI 1.5 to 3.1)), increasing age (OR 1.08; (95% CI 1.05 to 1.1)), and older age at sexual debut was protective (OR 0.87; (95% CI 0.83 to 0.93)). HSV-2 incidence during follow-up was significantly associated with female gender (HR 3.5; (95% CI 1.6 to 8.0)), having an HSV-2 positive partner (HR 4.9; (95% CI, 2.0 to 9.9)), and history of any other STI (HR 2.6; (95% CI 1.3 to 5.8)). Conclusions This is the first large study to report the prevalence and incidence of HSV-2 among sexual partners who are in a stable HIV-1 discordant relationship. Female gender, a history of any other STI, and having an HSV-2 positive partner were associated with an increased risk of acquiring HSV-2. 11 individuals a majority of them with HIV acquired HSV-2 during follow-up despite being in HSV-2 concordant negative relationship at enrolment. The high incidence of HSV-2 in couples who were initially HSV-2 concordant negative or HSV-2 discordant highlights the dire need for continuing comprehensive STD prevention programs particularly among high risk population Sub-Saharan Africa.

INTRODUCTION:More new HIV-1 infections occur within stable HIV-1-discordant couples than in any other group in Africa, and sexually transmitted infections (STIs) may increase transmission risk among discordant couples, accounting for a large proportion of new HIV-1 infections. Understanding correlates of STIs among discordant couples will aid in optimizing interventions to prevent HIV-1 transmission in these couples. METHODS:HIV-1-discordant couples in which HIV-1-infected partners were HSV-2-seropositive were tested for syphilis, chlamydia, gonorrhea, and trichomoniasis, and HIV-1-uninfected partners were tested for HSV-2. We assessed sociodemographic, behavioral, and biological correlates of a current STI. RESULTS:Of 416 couples enrolled, 16% were affected by a treatable STI, and among these both partners were infected in 17% of couples. A treatable STI was found in 46 (11%) females and 30 (7%) males. The most prevalent infections were trichomoniasis (5.9%) and syphilis (2.6%). Participants were 5.9-fold more likely to have an STI if their partner had an STI (P