A Longitudinal Analysis of the Impact of Health Behavior Campaigns on HIV-Risk Behaviors and HIV Incidence in Eswatini.

Between 2010 and 2015, Eswatini conducted mass media health behavior campaigns (HBCs) designed to avert new HIV infections. Using longitudinal data from the nationally representative Swaziland HIV Incidence Measurement Survey of 2011, we describe the impact of exposure to HBCs on selected HIV risk behaviors and HIV incidence among sexually active, HIV-negative adults (n = 11,232). Exposure to partner reduction HBCs was significantly associated with reporting fewer (i.e., 1 versus 2, or 2 versus ≥ 3) sexual partners in the prior 6 months at baseline among women (aOR = 3.02; 95% CI 1.38, 6.62); and at both baseline and at 6-months follow-up for men (aOR = 2.26; 95% CI 1.49, 3.44; aOR = 1.95, 95% CI [1.26-3.00], respectively). Despite these reported partner reductions, there was no association between HBC exposure and prospectively observed HIV seroconversions (n = 121). This analysis strengthens the evidence that HIV prevention at the population level requires integrated strategies.

Evidence on the effectiveness of community-based primary health care in improving HIV/AIDS outcomes for mothers and children in low- and middle-income countries: Findings from a systematic review.

BACKGROUND: The effectiveness of community-based primary health care (CBPHC) interventions in low- and middle-income countries (LMICs), especially for maternal, neonatal and child health, is well established. However, there has not been a systematic review of the literature on the effectiveness of CBPHC on HIV outcomes derived from rigorous assessments of primary studies. Using peer-reviewed studies of randomized interventions or those containing a specified control group and directly measuring clinical HIV outcomes, we provide evidence for the effectiveness of CBPHC on HIV outcomes for mothers and children in low- and middle-income countries (LMICs). METHODS: Eligibility criteria included studies assessing the effectiveness of community-based HIV interventions with or without a facility-based component, or multiple integrated projects, with outcome measures defining an aspect of HIV health status such as the utilization of prevention or health care services, nutritional status, serious morbidity (including clinical measures of HIV progression) or mortality of children aged five or younger and pregnant women. Articles published through June 3, 2020 were identified by searching four databases. The type of community-based projects implemented, the implementors, and the implementation strategies of each program were identified and the impact on HIV-related outcomes assessed. RESULTS: The search yielded 10 537 articles; 4881 underwent title and abstract screening after removing duplicates. Of these, 117 studies qualified for full-text screening; only 22 were included in the final analysis. Most studies showed that community-based interventions improved HIV prevention and treatment outcomes compared to facility-based approaches alone. Each study had at least one statistically significant HIV-related outcome; the non-significant outcomes found in six of the 22 studies were mostly not related to HIV programming. Most interventions were implemented by community health workers; other implementers were government workers, community members, or research staff. Strategies used included peer-to-peer education, psychosocial support, training of community champions, community-based follow-up care, home-based care, and integrated care. CONCLUSIONS: CBPHC strategies are effective in improving population-based, HIV-related health outcomes for mothers and children, especially in combination with facility-based approaches. However, there is a need to assess the scalability of such interventions and integrate them into existing health systems to assess their impact on the HIV pandemic in more routine settings.

Optimizing PMTCT efforts by repeat HIV testing during antenatal and perinatal care in resource-limited settings: A longitudinal assessment of HIV seroconversion.

BACKGROUND: Mother to child transmission (MTCT) of HIV remains a challenge in resource-limited settings. Central to elimination of MTCT is effective Provider Initiated HIV Counseling and Testing (PICT). Research has shown that conducting PICT only at the initial antenatal care (ANC) visit fails to benefit pregnant women who seroconvert later in their pregnancy. This study aimed to determine the most cost effective time to perform repeat HIV testing during ANC and perinatal care (PNC). METHODS: We studied the repeat HIV testing results of pregnant women ≥ 18 and adolescent girls aged 15-17 in the Sauri, Kenya Millennium Villages Project (MVP) site. Nurses provided HIV screening to 1,403 expectant women and 256 adolescent girls following the 1st, 2nd, 3rd and 4th ANC visits, at birth and 6 and 14 weeks postpartum. RESULTS: Five women seroconverted during the study period (incidence proportion 0.41%). One woman seroconverted at the 2nd ANC visit, another one at the 3rd, two at the 4th and one at 6 weeks post-partum. Of all the women who seroconverted, four reported an HIV negative primary partner, while one reported an unknown partner status. None of the participants reported condom use during pregnancy. Two of the seroconverters vertically transmitted HIV to their babies. The results did not suggest a clear pattern of seroconversion during ANC and PNC. CONCLUSIONS: The low rates of seroconversion suggest that testing pregnant women multiple times during ANC and PNC may not be cost effective, but a follow-up test during birth may be protective of the newborn.

The impact of "male clinics" on health-seeking behaviors of adult men in rural Kenya.

BACKGROUND: In most parts of the world, men access health services less frequently than women, and this trend is unrelated to differences in need for services. While male involvement in healthcare as partners or fathers has been extensively studied, less is known about the health-seeking behavior of men as clients themselves. This interventional research study aimed to determine how the introduction of male-friendly clinics impacted male care-seeking behavior and to describe the reasons for accessing services among men in rural Kenya. METHODS AND FINDINGS: We questioned men to assess utilization and perceptions of existing health clinics, then designed and evaluated a "male clinics" intervention where dedicated male health workers were hired for one year to offer routine, free services exclusively to men within existing healthcare facilities. Results were compared between data from Male Clinics in specific health facilities, the same facilities concurrently, nearby control facilities concurrently, and intervention facilities historically. Costs of services, distance to facilities, and quality of care were the main barriers to healthcare access reported. The number of total visits was significantly higher than control groups (p<0·0001). In the intervention group, 18·6% of visits were for a checkup compared to almost none in control groups. The most common diagnoses overall were upper respiratory tract infections, malaria and injury. A major limitation of this study is the non-comparability in information captured using the Male Clinic registers compared to control registers. CONCLUSIONS: Costs and quality of services deter men from seeking healthcare. The introduction of male-friendly health services could encourage men to seek preventive care and increase service uptake.

Pharmacokinetics and Pharmacodynamics of Tenofovir Reduced-Glycerin 1% Gel in the Rectal and Vaginal Compartments in Women: A Cross-Compartmental Study With Directly Observed Dosing.

BACKGROUND: Evidence is lacking regarding whether vaginal pre-exposure prophylaxis with topical tenofovir (TFV) reduces the risk of rectal HIV acquisition. SETTING: Bronx, NY. METHODS: MTN-014 was a phase 1, cross-over, randomized sequence trial comparing the cross-compartment pharmacokinetics and pharmacodynamics of daily TFV reduced-glycerin 1% gel after 14 days each of rectal and vaginal application, with directly observed dosing and a 6-week washout period between phases. RESULTS: Fourteen HIV-uninfected women enrolled; 91% of doses were observed and 13 women completed all study procedures. TFV and TFV diphosphate (TFV-DP) were detected in most samples collected from the dosing compartment. After vaginal dosing, TFV was detected in 10/14 samples of rectal fluid (RF) (median 4.4 ng/sponge) and 1/13 rectal tissue samples (0.2 ng/mg); TFV-DP was detected in 2/13 rectal tissue samples at 59.8 and 76.5 fmol/mg. After rectal dosing, TFV was detected in 9/14 samples of vaginal fluid (median 1.1 ng/swab) and in 6/14 vaginal tissue samples (median below limit of quantification); TFV-DP was detected in 3/14 vaginal tissue samples at 17.3, 87.6, and 77.1 fmol/mg. Neither cervicovaginal lavage fluid nor RF collected 24 hours after rectal or vaginal dosing resulted in a statistically significant suppression of viral replication. CONCLUSIONS: In this study of 14 days each of vaginal and rectal application of TFV reduced-glycerin 1% gel, we found only a small degree of cross-compartment distribution of TFV in RF and vaginal fluids and no pharmacodynamic activity in ex vivo testing. Although high TFV concentrations in the dosing compartment may be protective, low cross-compartment tissue concentrations are not likely to be protective.

Evaluation of the impact of a mobile health system on adherence to antenatal and postnatal care and prevention of mother-to-child transmission of HIV programs in Kenya.

BACKGROUND: The Millennium Villages Project (MVP) implemented in Western Kenya a mobile Health tool that uses text messages to coordinate Community Health Worker (CHW) activities around antenatal care (ANC) and Prevention of Mother-to-Child Transmission of HIV (PMTCT), named the ANC/PMTCT Adherence System (APAS). METHODS: End-user changes in health-seeking behavior in ANC and postnatal care (PNC) were investigated following registration of 800 women into APAS. These investigations employed interviews of pregnant women or new mothers (n = 67) and CHWs (n = 20). Ordinal logistic regressions and exact binomial tests were used in the routine data analyses (n = 650, health registers). RESULTS: All CHWs interviewed agreed that APAS helped them track pregnant woman efficiently, compared to paper-based tracking forms. Women registered in APAS reported that CHWs reminded them of appointments more regularly than before its inception. The routine data analysis showed that among women who had their 1(st) ANC visit in the 2(nd) trimester, women who resided in the MVP cluster and were in APAS had: 3 times the odds of going for more ANC visits compared to women who were not registered (but resided in the cluster), after adjusting for the mother's HIV status in the multivariate model (Adjusted OR = 2.58, 95% CI [1.10-6.01]); twice the odds of going for more ANC visits compared to women who were not registered and resided outside the cluster (Adjusted OR = 2.37, 95% CI [0.99-5.67]) Among women not registered, residence inside or outside the cluster did not affect the number of ANC visits made (Adjusted OR = 0.86, 95% CI [0.45-1.69]). The APAS also greatly increased the likelihood of women making the 6 recommended post-delivery baby follow-ups. For women registered in APAS, the MTCT rate at 18 months was significantly different from that of women not registered, and from the global rate of 30%. Women not registered had a 9% MTCT rate at 18 months regardless of residence, while women registered had a 0% transmission rate at both 9 and 18 months. CONCLUSIONS: The incorporation of mHealth tools in CHW programs can improve adherence to ANC and PNC and enhance PMTCT efforts.

Diverse secreted effectors are required for Salmonella persistence in a mouse infection model.

Salmonella enterica serovar Typhimurium causes typhoid-like disease in mice and is a model of typhoid fever in humans. One of the hallmarks of typhoid is persistence, the ability of the bacteria to survive in the host weeks after infection. Virulence factors called effectors facilitate this process by direct transfer to the cytoplasm of infected cells thereby subverting cellular processes. Secretion of effectors to the cell cytoplasm takes place through multiple routes, including two separate type III secretion (T3SS) apparati as well as outer membrane vesicles. The two T3SS are encoded on separate pathogenicity islands, SPI-1 and -2, with SPI-1 more strongly associated with the intestinal phase of infection, and SPI-2 with the systemic phase. Both T3SS are required for persistence, but the effectors required have not been systematically evaluated. In this study, mutations in 48 described effectors were tested for persistence. We replaced each effector with a specific DNA barcode sequence by allelic exchange and co-infected with a wild-type reference to calculate the ratio of wild-type parent to mutant at different times after infection. The competitive index (CI) was determined by quantitative PCR in which primers that correspond to the barcode were used for amplification. Mutations in all but seven effectors reduced persistence demonstrating that most effectors were required. One exception was CigR, a recently discovered effector that is widely conserved throughout enteric bacteria. Deletion of cigR increased lethality, suggesting that it may be an anti-virulence factor. The fact that almost all Salmonella effectors are required for persistence argues against redundant functions. This is different from effector repertoires in other intracellular pathogens such as Legionella.

RNA type III secretion signals that require Hfq.

Salmonella virulence is largely mediated by two type III secretion systems (T3SS) that deliver effector proteins from the bacterium to a host cell; however, the secretion signal is poorly defined. Effector N termini are thought to contain the signal, but they lack homology, possess no identifiable motif, and adopt intrinsically disordered structures. Alternative studies suggest that RNA-encoded signals may also be recognized and that they can be located in the 5' untranslated leader sequence. We began our study by establishing the minimum sequence required for reporter translocation. Untranslated leader sequences predicted from 42 different Salmonella effector proteins were fused to the adenylate cyclase reporter (CyaA'), and each of them was tested for protein injection into J774 macrophages. RNA sequences derived from five effectors, gtgA, cigR, gogB, sseL, and steD, were sufficient for CyaA' translocation into host cells. To determine the mechanism of signal recognition, we identified proteins that bound specifically to the gtgA RNA. One of the unique proteins identified was Hfq. Hfq had no effect upon the translocation of full-length CigR and SteD, but injection of intact GtgA, GogB, and SseL was abolished in an hfq mutant, confirming the importance of Hfq. Our results demonstrated that the Salmonella pathogenicity island 2 (SPI-2) T3SS assembled into a functional apparatus independently of Hfq. Since particular effectors required Hfq for translocation, Hfq-RNA complexes may participate in signal recognition.