Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1–Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda

BackgroundAntiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.ConclusionsIntegrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.     

Prevalence and Factors Associated with Sexually Transmitted Infections among HIV Positive Women Opting for Intrauterine Contraception

Background

Women living with HIV/AIDS (WLHA) are a high risk group for sexually transmitted infections (STIs). However, the majority of women with STIs are asymptomatic. Data on prevalence of STIs among WLHA in Uganda are limited. The objective of the study was to determine prevalence and factors associated with STIs among WLHA opting for intrauterine contraceptive device (IUD).

Methods

Three hundred fifty one WLHA deemed free of STIs using a syndromic logarithm were enrolled into the study. Endo-cervical swabs were taken before IUD insertion and PCR test for Nisseria gonorrhea (NG), Trichomonas vaginalis (TV) and Chlamydia trachomatis (CT) infections conducted.

Results

Participants’ mean age was 29.4 ± 6.2 years, 83% were under 35years, 50% had secondary education and 73% were married. The majority (69%) had disclosed their HIV sero status to their spouses, 82% used Cotrimoxazole prophylaxis, 70% were on antiretroviral therapy, 90% had CD4 count greater than 350, about 60% reported condoms use and 70% were of parity 2-4. Over 50% of the participants’ spouses were older than 35 years and 72% had attained secondary education. STIs prevalence was 11.1%, (95% CI 7.8-14.4) and individual prevalence for TV, NG, and CT was 5.9%, 5.4% and 0.9% respectively. Factors independently associated with STI were having primary or less education (OR= 2.3, 95% CI: 1.09 - 4.85) having a spouse of primary or less education (OR= 3.3, 95% CI: 1.6 - 6.78) and muslim faith (OR= 0.2, 95% CI: 0.04 - 0.78).

Conclusion

STI prevalence was 11.1%. TV and NG were the commonest STIs in this population. Having primary or less education for both participant and spouse was associated with increased risk while being of muslim faith was associated with reduced risk of STI.     

Artemether-lumefantrine to treat malaria in pregnancy is associated with reduced placental haemozoin deposition compared to quinine in a randomized controlled trial

ABSTRACT: BACKGROUND: Data on efficacy of artemisinin-based combination therapy (ACT) to treat Plasmodium falciparum during pregnancy in sub-Saharan Africa is scarce. A recent open label, randomized controlled trial in Mbarara, Uganda demonstrated that artemether-lumefantrine (AL) is not inferior to quinine to treat uncomplicated malaria in pregnancy. Haemozoin can persist in the placenta following clearance of parasites, however there is no data whether ACT can influence the amount of haemozoin or the dynamics of haemozoin clearance. METHODS: Women attending antenatal clinics with weekly screening and positive blood smears by microscopy were eligible to participate in the trial and were followed to delivery. Placental haemozoin deposition and inflammation were assessed by histology. To determine whether AL was associated with increased haemozoin clearance, population haemozoin clearance curves were calculated based on the longitudinal data. RESULTS: Of 152 women enrolled in each arm, there were 97 and 98 placental biopsies obtained in the AL and quinine arms, respectively. AL was associated with decreased rates of moderate to high grade haemozoin deposition (13.3% versus 25.8%), which remained significant after correcting for gravidity, time of infection, re-infection, and parasitaemia. The amount of haemozoin proportionately decreased with the duration of time between treatment and delivery and this decline was greater in the AL arm. Haemozoin was not detected in one third of biopsies and the prevalence of inflammation was low, reflecting the efficacy of antenatal care with early detection and prompt treatment of malaria. CONCLUSIONS: Placental haemozoin deposition was decreased in the AL arm demonstrating a relationship between pharmacological properties of drug to treat antenatal malaria and placental pathology at delivery. Histology may be considered an informative outcome for clinical trials to evaluate malaria control in pregnancy. Trial registration REGISTRY: http://clinicaltrials.gov/ct2/show/NCT00495508.     

Stratified Whole Genome Linkage Analysis of Chiari Type I Malformation Implicates Known Klippel-Feil Syndrome Genes as Putative Disease Candidates

Chiari Type I Malformation (CMI) is characterized by displacement of the cerebellar tonsils below the base of the skull, resulting in significant neurologic morbidity. Although multiple lines of evidence support a genetic contribution to disease, no genes have been identified. We therefore conducted the largest whole genome linkage screen to date using 367 individuals from 66 families with at least two individuals presenting with nonsyndromic CMI with or without syringomyelia. Initial findings across all 66 families showed minimal evidence for linkage due to suspected genetic heterogeneity. In order to improve power to localize susceptibility genes, stratified linkage analyses were performed using clinical criteria to differentiate families based on etiologic factors. Families were stratified on the presence or absence of clinical features associated with connective tissue disorders (CTDs) since CMI and CTDs frequently co-occur and it has been proposed that CMI patients with CTDs represent a distinct class of patients with a different underlying disease mechanism. Stratified linkage analyses resulted in a marked increase in evidence of linkage to multiple genomic regions consistent with reduced genetic heterogeneity. Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of “CTD-negative” families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS). Interestingly, roughly 3–5% of CMI patients are diagnosed with KFS. In order to investigate the possibility that CMI and KFS are allelic, GDF3 and GDF6 were sequenced leading to the identification of a previously known KFS missense mutation and potential regulatory variants in GDF6. This study has demonstrated the value of reducing genetic heterogeneity by clinical stratification implicating several convincing biological candidates and further supporting the hypothesis that multiple, distinct mechanisms are responsible for CMI.     

Studies of Hypervalent Iron

The iron (IV), (V) and (VI) oxidation states are of great interest because of their role in catalytic oxidation/ hydroxylation reactions. This report summarizes the information currently available on the kinetic and chemical properties of the water-soluble ions of FeO²₄-, FeO^3-₄ and FeO^4-₄, their prorogated forms. and/or simple complex derivatives. The discussion includes their radiation-induced formation, decay kinetics, reactivity with other compounds, determination of their respective pK_a, values as well as spectral properties.     

Kinetics of some electron-transfer reactions in biological Photosystems II. Study of intramolecular electron-transfer rates between ferredoxin-NADP reductase, NADP radical and oxidized ferredoxin

It has been shown by the pulse radiolysis technique that radiation-generated NADP free radicals (NADP·) first combine with ferredoxin-NADP reductase and then transfer the odd electron by a fast intramolecular process to the enzyme flavin moiety yielding the semiquinone (ferredoxin-NADP reductase, FNR-FADH·). The corresponding first-order rate constant k₁₅ varies with ionic strength from 2.6·10³ s⁻¹ at I = 0.66 M to 2.3·10⁴ s⁻¹ at I = 0.005 M In the presence of ferredoxin-NADP reductase-bound oxidized ferredoxin, the electron cascades, thus further reducing the ferredoxin. The transfer of the electron from the flavin semiquinone (ferredoxin-NADP reductase, FNR-FADH·) to the bound oxidized ferredoxin proceeds at a rate of k₁₈ = 2.36 s⁻¹. This process approaches an equilibrium condition which is in favor of the reverse reaction suggesting that k₋₁₈ > k₁₈.     

Use of Modern Family Planning Methods in Fishing Communities of Lake Victoria,Uganda

Introduction

Fishing communities (FCs) in Uganda have high HIV infection rates but poor access to health services including family planning (FP). Although FP is a cost-effective public health intervention, there is a paucity of data on knowledge and use of modern FP in FCs. This study determined knowledge and use of modern FP methods in FCs of Uganda.

Methods

Data were accrued from a 12-month follow up of 1,688 HIV-uninfected individuals, 18–49 years from 8 FCs along Lake Victoria, between September 2011 and March 2013. Data on knowledge and use of modern FP were collected through a semi-structured questionnaire. Prevalence Risk Ratios with corresponding 95% CIs were used to determine factors associated with Modern FP knowledge and use.

Results

The mean age was 31.4 years, with nearly half (48.8%) being females while more than half (58.6%) had attained up to primary education level. Knowledge of modern FP was high, 87.5% (1477/1688); significantly higher among females [adj. PRR = 4.84 (95% CI; 3.08, 7.61)], among older respondents (25–29 years) [adj. PRR = 1.83 (95% CI; 1.12, 2.99)] compared to younger ones (18–24 years) and among those conducting business [adj. PRR = 2.42(95% CI; 1.02, 5.74)] relative to those primarily in fishing. Just over a third (35.2%, 595/1688) reported use of at least one modern FP method. Use of modern FP methods was significantly higher among females [adj. PRR = 2.04 (95% CI; 1.56, 2.65, and among those reporting multiple sexual partnerships [adj. PRR = 2.12, 95% CI; 1.63, 2.76)]. Nonuse of modern methods was mostly due to desire for more children (30.6%), fear of side effects (12.2%) and partner refusal (5.2%).

Conclusion

Despite their high knowledge of FP, FCs have low use of modern FP methods. Key barriers to use of modern FP methods were high fertility desires, fear of perceived side effects and partner refusal of methods.     

High Levels of Adherence and Viral Suppression in a Nationally Representative Sample of HIV-Infected Adults on Antiretroviral Therapy for 6, 12 and 18 Months in Rwanda

Background

Generalizable data are needed on the magnitude and determinants of adherence and virological suppression among patients on antiretroviral therapy (ART) in Africa.

Methods

We conducted a cross-sectional survey with chart abstraction, patient interviews and site assessments in a nationally representative sample of adults on ART for 6, 12 and 18 months at 20 sites in Rwanda. Adherence was assessed using 3- and 30-day patient recall. A systematically selected sub-sample had viral load (VL) measurements. Multivariable logistic regression examined predictors of non-perfect (<100%) 30-day adherence and detectable VL (>40 copies/ml).

Results

Overall, 1,417 adults were interviewed and 837 had VL measures. Ninety-four percent and 78% reported perfect adherence for the last 3 and 30 days, respectively. Eighty-three percent had undetectable VL. In adjusted models, characteristics independently associated with higher odds of non-perfect 30-day adherence were: being on ART for 18 months (vs. 6 months); younger age; reporting severe (vs. no or few) side effects in the prior 30 days; having no documentation of CD4 cell count at ART initiation (vs. having a CD4 cell count of <200 cells/µL); alcohol use; and attending sites which initiated ART services in 2003–2004 and 2005 (vs. 2006–2007); sites with ≥600 (vs. <600 patients) on ART; or sites with peer educators. Participation in an association for people living with HIV/AIDS; and receiving care at sites which regularly conduct home-visits were independently associated with lower odds of non-adherence. Higher odds of having a detectable VL were observed among patients at sites with peer educators. Being female; participating in an association for PLWHA; and using a reminder tool were independently associated with lower odds of having detectable VL.

Conclusions

High levels of adherence and viral suppression were observed in the Rwandan national ART program, and associated with potentially modifiable factors.