Alcohol use among people who inject drugs living with HIV in Kenya is associated with needle sharing, more new sex partners, and lower engagement in HIV care.

We assessed the prevalence and correlates of alcohol use among 870 people who inject drugs living with HIV in Kenya, with attention toward (1) sexual and injecting risk behaviors for HIV transmission and (2) HIV care engagement. We defined heavy alcohol use as > 14 drinks/week for men and > 7 drinks/week for women, moderate alcohol use as any lesser but non-zero amount, and any alcohol use as either moderate or heavy use. Approximately 39% of participants reported any alcohol use and 15% heavy use. In multivariate analysis, any alcohol use compared to no use was associated with needle sharing, > 3 new sex partners in the past 3 months, being unaware of HIV status, never enrolling in HIV care, and not being on ART (all p < 0.05). Heavy alcohol use as compared to no use was associated with needle sharing (aOR = 2.72; 95% CI 1.43, 5.13), injection equipment sharing (aOR = 1.80; 95% CI 1.00, 3.16), > 3 new sex partners in the past 3 months (aOR = 1.99; 95% CI 1.12, 3.49), and being unaware of HIV status (aOR = 2.77; 95% CI 1.46, 5.19). There was no association between any measure of alcohol use and unsuppressed viral load. Alcohol use among people who inject drugs living with HIV may carry elevated risk of HIV transmission mediated by sexual and injecting practices and is associated with lower engagement in multiple stages of the HIV care cascade.

External validation of models to predict the outcome of pregnancies of unknown location: a multicentre cohort study.

OBJECTIVE: To validate externally five approaches to predict ectopic pregnancy (EP) in pregnancies of unknown location (PUL): the M6P and M6NP risk models, the two-step triage strategy (2ST, which incorporates M6P), the M4 risk model, and beta human chorionic gonadotropin ratio cut-offs (BhCG-RC). DESIGN: Secondary analysis of a prospective cohort study. SETTING: Eight UK early pregnancy assessment units. POPULATION: Women presenting with a PUL and BhCG >25 IU/l. METHODS: Women were managed using the 2ST protocol: PUL were classified as low risk of EP if presenting progesterone ≤2 nmol/l; the remaining cases returned 2 days later for triage based on M6P. EP risk ≥5% was used to classify PUL as high risk. Missing values were imputed, and predictions for the five approaches were calculated post hoc. We meta-analysed centre-specific results. MAIN OUTCOME MEASURES: Discrimination, calibration and clinical utility (decision curve analysis) for predicting EP. RESULTS: Of 2899 eligible women, the primary analysis excluded 297 (10%) women who were lost to follow up. The area under the ROC curve for EP was 0.89 (95% CI 0.86-0.91) for M6P, 0.88 (0.86-0.90) for 2ST, 0.86 (0.83-0.88) for M6NP and 0.82 (0.78-0.85) for M4. Sensitivities for EP were 96% (M6P), 94% (2ST), 92% (N6NP), 80% (M4) and 58% (BhCG-RC); false-positive rates were 35%, 33%, 39%, 24% and 13%. M6P and 2ST had the best clinical utility and good overall calibration, with modest variability between centres. CONCLUSIONS: 2ST and M6P performed best for prediction and triage in PUL. TWEETABLE ABSTRACT: The M6 model, as part of a two-step triage strategy, is the best approach to characterise and triage PULs.

Triaging women with pregnancy of unknown location using two-step protocol including M6 model: clinical implementation study.

OBJECTIVE: The M6 risk-prediction model was published as part of a two-step protocol using an initial progesterone level of ≤ 2 nmol/L to identify probable failing pregnancies (Step 1) followed by the M6 model (Step 2). The M6 model has been shown to have good triage performance for stratifying women with a pregnancy of unknown location (PUL) as being at low or high risk of harboring an ectopic pregnancy (EP). This study validated the triage performance of the two-step protocol in clinical practice by evaluating the number of protocol-related adverse events and how effectively patients were triaged. METHODS: This was a prospective multicenter interventional study of 3272 women with a PUL, carried out between January 2015 and January 2017 in four district general hospitals and four university teaching hospitals in the UK. The final pregnancy outcome was defined as: a failed PUL (FPUL), an intrauterine pregnancy (IUP) or an EP (including persistent PUL (PPUL)). FPUL and IUP were grouped as low-risk and EP/PPUL as high-risk PUL. Serum progesterone and human chorionic gonadotropin (hCG) levels were measured at presentation in all patients. If the initial progesterone level was ≤ 2 nmol/L, patients were discharged and were asked to have a follow-up urine pregnancy test in 2 weeks to confirm a negative result. If the progesterone level was > 2 nmol/L or a measurement had not been taken, hCG level was measured again at 48 h and results were entered into the M6 model. Patients were managed according to the outcome predicted by the protocol. Those classified as 'low risk, probable FPUL' were advised to perform a urine pregnancy test in 2 weeks and those classified as 'low risk, probable IUP' were invited for a scan a week later. When a woman with a PUL was classified as high risk (i.e. risk of EP ≥ 5%) she was reviewed clinically within 48 h. One center used a progesterone cut-off of ≤ 10 nmol/L and its data were analyzed separately. If the recommended management protocol was not adhered to, this was recorded as a protocol deviation and classified as: unscheduled visit for clinician reason, unscheduled visit for patient reason or incorrect timing of blood test or ultrasound scan. The classifications outlined in the UK Good Clinical Practice (GCP) guidelines were used to evaluate the incidence of adverse events. Data were analyzed using descriptive statistics. RESULTS: Of the 3272 women with a PUL, 2625 were included in the final analysis (317 met the exclusion criteria or were lost to follow-up, while 330 were evaluated using a progesterone cut-off of ≤ 10 nmol/L). Initial progesterone results were available for 2392 (91.1%) patients. In Step 1, 407 (15.5%) patients were classified as low risk (progesterone ≤ 2 nmol/L), of whom seven (1.7%) were ultimately diagnosed with an EP. In 279 of the remaining 2218 women with a PUL, the M6 model was not applied owing to protocol deviation or because the outcome was already known (usually on the basis of an ultrasound scan) before a second hCG reading was taken; of these patients, 30 were diagnosed with an EP. In Step 2, 1038 women with a PUL were classified as low risk, of whom eight (0.8%) had a final outcome of EP. Of 901 women classified as high risk at Step 2, 275 (30.5%) had an EP. Therefore, 275/320 (85.9%) EPs were correctly classified as high risk. Overall, 1445/2625 PUL (55.0%) were classified as low risk, of which 15 (1.0%) were EP. None of these cases resulted in a ruptured EP or significant clinical harm. Sixty-two women participating in the study had an adverse event, but no woman had a serious adverse event as defined in the UK GCP guidelines. CONCLUSIONS: This study has shown that the two-step protocol incorporating the M6 model effectively triaged the majority of women with a PUL as being at low risk of an EP, minimizing the follow-up required for these patients after just two visits. There were few misclassified EPs and none of these women came to significant clinical harm or suffered a serious adverse clinical event. The two-step protocol incorporating the M6 model is an effective and clinically safe way of rationalizing the management of women with a PUL. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

T cell anergy and activation are associated with suboptimal humoral responses to measles revaccination in HIV-infected children on anti-retroviral therapy in Nairobi, Kenya.

HIV-infected children are less capable of mounting and maintaining protective humoral responses to vaccination against measles compared to HIV-uninfected children. This poses a public health challenge in countries with high HIV burdens. Administration of anti-retroviral therapy (ART) and revaccinating children against measles is one approach to increase measles immunity in HIV-infected children, yet it is not effective in all cases. Immune anergy and activation during HIV infection are factors that could influence responses to measles revaccination. We utilized a flow cytometry-based approach to examine whether T cell anergy and activation were associated with the maintenance of measles-specific immunoglobulin (Ig)G antibodies generated in response to measles revaccination in a cohort of HIV-infected children on ART in Nairobi, Kenya. Children who sustained measles-specific IgG for at least 1 year after revaccination displayed significantly lower programmed cell death 1 (PD-1) surface expression on CD8(+) T cells on a per-cell basis and exhibited less activated CD4(+) T cells compared to those unable to maintain detectable measles-specific antibodies. Children in both groups were similar in age and sex, CD4(+) T cell frequency, duration of ART treatment and HIV viral load at enrolment. These data suggest that aberrant T cell anergy and activation are associated with the impaired ability to sustain an antibody response to measles revaccination in HIV-infected children on ART.

Decreased incidence of sexually transmitted diseases among trucking company workers in Kenya: results of a behavioural risk-reduction programme.

OBJECTIVE: To establish a cohort of high-risk individuals suitable for HIV-prevention trials, and to measure changes in sexual behaviour and sexually transmitted disease (STD) incidence after a behavioural intervention. DESIGN: Prospective cohort study in trucking company depots in Mombasa, Kenya. PARTICIPANTS: A total of 556 male HIV-seronegative employees of trucking companies. INTERVENTIONS: HIV serological testing, individual counselling, condom promotion, STD diagnosis and management. MAIN OUTCOME MEASURES: Sexual risk behaviour and symptomatic STD incidence. RESULTS: Using time-trend modelling, significant declines in self-reported high-risk sexual behaviour were demonstrated during a 1-year follow-up. The percentage of men reporting any extramarital sex during the 3-month period prior to a follow-up visit decreased from 49% durig the first quarter of follow-up to 36% during the last quarter (P < 0.001). The decline in reported female sex worker contact was from 12% to 6% (P = 0.001). Approximately 30% of men reported consistent condom use during extramarital sex and this percentage remained unchanged during the study period. The incidence of STD declined from 34 per 100 person years (PY) during the first quarter to 10 per 100 PY during the last quarter (P = 0.001). Significant reductions in gonorrhoea (15 to five cases per 100 PY, P = 0.04), non-gonococcal urethritis (10 to two cases per 100 PY, P = 0.05), and genital ulcer disease (nine to two cases per 100 PY, P = 0.02) were observed. CONCLUSIONS: Among truck company workers who participated in a cohort study in Mombasa, Kenya, there was a significant decrease in sex with high-risk partners, but no change in condom use. The change in heterosexual risk behaviour was accompanied by a significant decrease in incidence of gonorrhoea, non-gonococcal urethritis, and genital ulcer disease.

PIP: 556 male HIV-seronegative male employees of trucking companies in Mombasa, Kenya, were exposed to HIV serological testing, individual counseling, condom promotion, and sexually transmitted disease (STD) diagnosis and management, and returned for at least one follow-up visit in a prospective study to measure changes in sexual behavior and STD incidence after the intervention. There was a significant decrease in sex with high-risk partners over the 1-year period of follow-up, but no change in condom use among study participants; 30% of men reported consistent condom use during extramarital sex throughout the study period. The change in heterosexual risk behavior was accompanied by a significant decrease in the incidence of gonorrhea, nongonococcal urethritis, and genital ulcer disease. The percentage of men reporting extramarital sex decreased from 49% to 36%, while contact with female prostitutes declined from 12% to 6%.

CRB1 mutations may result in retinitis pigmentosa without para-arteriolar RPE preservation.

PURPOSE: To report a new phenotype in retinitis pigmentosa (RP) patients with CRB1 mutations at the RP12 locus. PATIENTS: Thirty-seven patients from two Pakistani families with severe retinitis pigmentosa. METHODS: Samples were screened with single-strand conformation polymorphism analysis followed by DNA sequencing of the coding sequence of the CRB1 gene. RESULTS: Two novel CRB1 mutations were discovered. No patients had evidence of preservation of the para-arteriolar retinal pigment epithelium (PPRPE) that has been previously reported in all cases of RP associated with CRB1 mutations. CONCLUSIONS: Patients with severe autosomal recessive (or simplex) RP who lack the finding of PPRPE should not be excluded from molecular analysis of CRB1 purely because they lack the clinical feature of PPRPE. This report illustrates that RP at the RP12 locus is not clinically uniform. The absence of PPRPE cannot be used to exclude CRB1 as a potential molecular explanation for RP.

Evaluation of a GP practice based homeopathy service.

This study aimed to evaluate the effect of a GP-led practice-based homeopathy service on symptoms, activity, wellbeing, general practice consultation rate and the use of conventional medications. Data were collected for 97 consecutive patients referred to a homeopathy service between 1 July 2002 and 23 January 2003. Self-rated symptom severity, activity limitation and wellbeing were scored on a seven-point scale at initial homeopathic consultation and via postal questionnaire at a mean follow-up time of 134 days. Primary symptoms improved by a mean of 2.49 points (95% confidence interval (CI) 2.08-2.90; P < 0.0001); secondary symptoms by 2.49 points (95% CI 2.00-2.98; P < 0.0001); ability to undertake activity by 2.43 points (95% CI 1.95-2.91; P < 0.0001) and wellbeing by 1.41 points (95% CI 1.02-1.80; P < 0.0001). Following use of the homeopathy service the mean 6-month general practice consultation rate decreased by 1.18 consultations per patient (95% CI 0.40-1.99; P = 0.004). Fifty-seven per cent of patients reduced or stopped taking their conventional medication, saving 2,807.30 Pounds per year. The main limitation of this study is the absence of a control group. The findings warrant further research including controlled studies and economic analysis.

Diversity in virus populations from genital secretions and peripheral blood from women recently infected with human immunodeficiency virus type 1.

In order to develop a human immunodeficiency virus type 1 vaccine with global efficacy, it is important to evaluate the virus populations that are transmitted to individuals living in high-incidence areas. To determine the nature of the human immunodeficiency virus type 1 population transmitted to women during heterosexual contact, we examined the diversity of the proviral envelope gene in infected cells in both genital secretions and peripheral blood from six recently seroconverted Kenyan women. Heterogeneous virus populations were present in cervical secretions and/or peripheral blood shortly after seroconversion for five of six infected individuals, and tissue-specific variants were identified in several cases.

PIP: The HIV-1 population in an infected individual often includes a diverse mix of variants distinguished mainly by differences in the extracellular envelope glycoprotein. Some variants may be favored for cell- and tissue-specific replication. In order to develop a HIV-1 vaccine which will be effective worldwide, researchers need to evaluate the virus populations which are transmitted to individuals living in high-incidence areas. The authors examined the diversity of the proviral envelope gene in infected cells in the genital secretions and peripheral blood of six recently seroconverted Kenyan female prostitutes in the attempt to determine the nature of the HIV-1 population transmitted to women during heterosexual contact. Heterogeneous virus populations were present in cervical secretions and/or peripheral blood shortly after seroconversion for five of the six women, and tissue-specific variants were identified in several cases. Study findings suggest that virus heterogeneity in the cohort was due to the transmission of multiple HIV-1 genotypes.

Aetiology, outcome, and risk factors for mortality among adults with acute pneumonia in Kenya.

BACKGROUND: Despite a substantial disease burden, there is little descriptive epidemiology of acute pneumonia in sub-Saharan Africa. We did this study to define the aetiology of acute pneumonia, to estimate mortality at convalescence, and to analyse mortality risk-factors. METHODS: We studied 281 Kenyan adults who presented to two public hospitals (one urban and one rural) with acute radiologically confirmed pneumonia during 1994-96. We did blood and lung-aspirate cultures, mycobacterial cultures, serotype-specific pneumococcal antigen detection, and serology for viral and atypical agents. FINDINGS: Aetiology was defined in 182 (65%) patients. Streptococcus pneumoniae was the most common causative agent, being found in 129 (46%) cases; Mycobacterium tuberculosis was found in 26 (9%). Of 255 patients followed up for at least 3 weeks, 25 (10%) died at a median age of 33 years. In multivariate analyses, risk or protective factors for mortality were age (odds ratio 1.51 per decade [95% CI 1.04-2.19]), unemployment (4.42 [1.21-16.1]), visiting a traditional healer (5.26 [1.67-16.5]), visiting a pharmacy (0.30 [0.10-0.91]), heart rate (1.64 per 10 beats [1.24-2.16]), and herpes labialis (15.4 [2.22-107]). HIV-1 seropositivity, found in 52%, was not associated with mortality. Death or failure to recover after 3 weeks was more common in patients with pneumococci of intermediate resistance to benzylpenicillin, which comprised 28% of pneumococcal isolates, than in those infected with susceptible pneumococci (5.60 [1.33-23.6]). INTERPRETATION: We suggest that tuberculosis is a sufficiently common cause of acute pneumonia in Kenyan adults to justify routine sputum culture, and that treatment with benzylpenicillin remains appropriate for clinical failure due to M. tuberculosis, intermediate-resistant pneumococci, and other bacterial pathogens. However, interventions restricted to hospital management will fail to decrease mortality associated with socioeconomic, educational, and behavioural factors.

Cervical shedding of herpes simplex virus in human immunodeficiency virus-infected women: effects of hormonal contraception, pregnancy, and vitamin A deficiency.

Genital shedding of herpes simplex virus (HSV) results in frequent transmission of infection to sexual partners and neonates. In a cross-sectional study, cervical shedding of HSV DNA was detected in 43 (17%) cervical swab samples from 273 women seropositive for HSV-1, HSV-2, and human immunodeficiency virus type 1 (HIV-1). Cervical shedding of HSV was significantly associated with oral contraception (adjusted odds ratio [aOR], 4.5; 95% confidence interval [CI], 1.7-12.2), use of depo-medroxyprogesterone acetate (aOR, 3.2; 95% CI, 1.3-7.7), and pregnancy (aOR, 7.9; 95% CI, 2.0-31.7). In the subgroup of women who were not pregnant and not using hormonal contraception (n=178), serum vitamin A was highly predictive of cervical HSV shedding: concentrations indicating severe deficiency, moderate deficiency, low-normal, and high-normal status were associated with 29%, 18%, 8%, and 2% prevalences of cervical HSV shedding, respectively (linear trend, P=.0002). Several factors appear to influence HSV reactivation in HIV-1 seropositive women.

Cervical shedding of herpes simplex virus and cytomegalovirus throughout the menstrual cycle in women infected with human immunodeficiency virus type 1.

OBJECTIVE: Our purpose was to evaluate the frequency and patterns of the shedding of herpes simplex virus and cytomegalovirus in the female genital tract throughout the menstrual cycle. STUDY DESIGN: Seventeen women, all seropositive for herpes simplex virus types 1 and 2, cytomegalovirus, and human immunodeficiency virus type 1, underwent daily evaluation of cervical viral shedding for the duration of 1 menstrual cycle (21-31 visits per woman). Serum estradiol and progesterone levels were monitored 3 times weekly. RESULTS: Overall, herpes simplex virus deoxyribonucleic acid was detected in 43 (10%) of 450 cervical swabs, and cytomegalovirus deoxyribonucleic acid was detected in 232 (52%) of 450 cervical swabs. For individual women there was considerable variability in the percentage of days on which virus was detected, ranging from 0% to 33% for herpes simplex virus and from 20% to 97% for cytomegalovirus. Shedding of herpes simplex virus did not vary significantly with menstrual cycle; however, shedding of cytomegalovirus was significantly more frequent in the luteal phase (odds ratio, 1.9; 95% confidence interval, 1.1-3.4). A CD4(+) lymphocyte count <200/microL was associated with increased frequency of the detection of herpes simplex virus (odds ratio, 5.7; 95% confidence interval, 1.1-29.4). CONCLUSIONS: Asymptomatic cervical shedding of both herpes simplex virus and cytomegalovirus occurs very frequently in women infected with human immunodeficiency virus type 1. The risk of transmitting these viruses to sexual partners and neonates may be higher than previously recognized.

Cervical and vaginal shedding of human immunodeficiency virus type 1-infected cells throughout the menstrual cycle.

Cervical and vaginal secretions from 17 women infected with human immunodeficiency virus type 1 (HIV-1) were evaluated daily through the course of one menstrual cycle for HIV-1 DNA (21-31 visits per woman). HIV-1-infected cells were detected in 207 (46%) of 450 endocervical swabs and 74 (16%) of 449 vaginal swabs. There was considerable variability in the percentage of positive swabs from each woman, ranging from 4% to 100% of endocervical swabs and from 0 to 71% of vaginal swabs. In multivariate analyses, plasma HIV-1 RNA was significantly associated with shedding of HIV-1-infected cells; each 1-unit increase in the log of plasma virus load was associated with a 5.6-fold increase in the odds of cervical shedding (95% confidence interval [CI], 2.1-14.8) and a 3.9-fold increase in the odds of vaginal shedding (95% CI, 2.1-7.2). There was no discernible pattern of genital tract shedding with phase of the menstrual cycle and no significant association with serum estradiol or progesterone levels.