Access to ART has increased dramatically in resource-limited settings since its introduction a decade ago. However, ART coverage remains low in countries with the highest disease burden, which may be partially explained by poor testing to care linkages. HIV testing service may impact early attrition in the HIV treatment cascade.
A retrospective cohort study was conducted in 18 clinics in central Mozambique using routine patient data and monthly reports. Patients referred from voluntary counseling and testing (VCT) were compared to patients referred from prevention of mother-to-child transmission (PMTCT) for three outcomes: 1) enrollment at an HIV clinic ≤ 30 days after testing HIV-positive, 2) CD4 test ≤ 30 days after enrollment, and 3) ART initiation ≤ 90 days after first CD4 test.
Patient retention in the HIV care system dropped at each step from HIV testing to ART initiation. Enrollment in HIV care was not significantly different between PMTCT and VCT (RR=0.84, 0.72
Poor linkages between HIV testing and care hamper efforts to improve coverage for HIV care and treatment services. Increased loss to follow-up among women diagnosed in PMTCT relative to VCT is worrisome, and merits further qualitative research and programmatic attention.
Linkages; HIV testing; Antiretroviral Therapy; Mozambique; HIV testing to care; Operations Research
Individual and sexual partner characteristics may increase risk of abnormal cervical cytology among women in 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. Lack of male circumcision, male HSV-2 seropositivity and lower couple socioeconomic status were associated with cervical abnormalities (p<0.05). HIV-uninfected women with HIV-infected male sex partners (CD4>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.
Cancer; cervical; cytology; discordant couples; HIV
Over the past decade, the University of Nairobi (UoN) has increased the number of enrolled medical students three-fold in response to the growing need for more doctors. This has resulted in a congested clinical training environment and limited opportunities for students to practice clinical skills at the tertiary teaching facility. To enhance the clinical experience, the UoN Medical Education Partnership Initiative Program undertook to train medical students in non-tertiary hospitals around the country under the mentorship of consultant preceptors at these hospitals. This study focused on the evaluation of the pilot decentralised training rotation.
The decentralised training program was piloted in October 2011 with 29 fourth-year medical students at four public hospitals for a seven-week rotation. We evaluated student and consultant experiences using a series of focus group discussions. A three-person team developed the codes for the focus groups and then individually and anonymously coded the transcripts. The teams’ findings were triangulated to confirm major themes.
Before the rotation, the students expressed the motivation to gain more clinical experience as they felt they lacked adequate opportunity to exercise clinical skills at the tertiary referral hospital. By the end of the rotation, the students felt they had been actively involved in patient care, had gained clinical skills and had learned to navigate socio-cultural challenges in patient care. They further expressed the wish to return to those hospitals for future practice. The consultants expressed their motivation to teach and mentor students and acknowledged that the academic interaction had positively impacted on patient care.
The decentralised training enhanced students’ learning by providing opportunities for clinical and community experiences and has demonstrated how practicing medical consultants can be engaged as preceptors in students learning. This training may also increase students’ ability and willingness to work in rural and underserved areas.
Decentralised training; clinical experience; medical students; clinical mentorship; consultant preceptors
Strategies to transfer international health research training programs to sub-Saharan African institutions focus on developing cadres of local investigators who will lead such programs. Using a critical leadership theory framework, we conducted a qualitative study of one program to understand how collaborative training and research can support early career investigators in Kenya toward the program transfer goal.
We used purposive sampling methods and a semi-structured protocol to conduct in-depth interviews with US (N = 5) and Kenyan (N = 5) independent investigators. Transcripts were coded using a two-step process, and then compared with each other to identify major themes.
A limited local research environment, funding needs and research career mentorship were identified as major influences on early career researchers. Institutional demands on Kenyan faculty to teach rather than complete research restricted investigators’ ability to develop research careers. This was coupled with lack of local funding to support research. Sustainable collaborations between Kenyan, US and other international investigators were perceived to mitigate these challenges and support early career investigators who would help build a robust local research environment for training.
Mutually beneficial collaborations between Kenyan and US investigators developed during training mitigate these challenges and build a supportive research environment for training. In these collaborations, early career investigators learn how to navigate the complex international research environment to build local HIV research capacity. Shared and mutually beneficial resources within international research collaborations are required to support early career investigators and plans to transfer health research training to African institutions.
Research capacity building; HIV; Early career investigators
In 2010, the World Health Organization shifted its malaria guidelines from recommending the empiric treatment of all febrile children to treating only those with laboratory-confirmed malaria. This study evaluated the frequency and predictors of malaria over-treatment among febrile malaria-negative children in Kenya.
Between 2012 and 2013, 1,362 children presenting consecutively with temperature ≥37.5°C to Kisii and Homa Bay hospitals were enrolled in a cross-sectional study evaluating causes of fever. Children were screened for malaria using smear microscopy and rapid diagnostic tests and managed according to standard of care at the hospitals. The frequency of anti-malarial prescriptions among children with laboratory-confirmed malaria negative children (malaria over-treatment) was determined; and clinical and demographic correlates of overtreatment evaluated using logistic regression. Because of differences in malaria endemicity, analyses were stratified and compared by site.
Among 1,362 children enrolled, 46 (7%) of 685 children in Kisii, and 310 (45.8%) of 677 in Homa Bay had laboratory-confirmed malaria; p < 0.001. Among malaria-negative children; 210 (57.2%) in Homa Bay and 45 (7.0%) in Kisii received anti-malarials; p < 0.001. Predictors of over-treatment in Homa Bay included ≥ one integrated management of childhood illness (IMCI) danger sign (aOR = 8.47; 95% CI: 4.81-14.89), fever lasting ≥ seven days (aOR = 4.94; 95% CI: 1.90-12.86), and fever ≥39°C (aOR = 3.07; 95% CI: 1.58-5.96). In Kisii, only fever ≥39°C predicted over-treatment (aOR = 2.13; 95% CI: 1.02-4.45).
Malaria over-treatment was common, particularly in Homa Bay, where the prevalence of malaria was extremely high. Severe illness and high or prolonged fever were associated with overtreatment. Overtreatment may result in failure to treat other serious causes of fever, drug resistance, and unnecessarily treatment costs.
Malaria; Laboratory testing; Over-treatment
There are limited data on prognostic utility of interferon-gamma (IFN-γ) release assays (IGRAs) for active tuberculosis (TB) among HIV-1 infected individuals.
Samples from a perinatal cohort of HIV-1 infected women in Kenya, obtained during pregnancy were tested using T-SPOT.TB IGRAs to detect Mycobacterium tuberculosis (MTB)-specific IFN-γ responses. IFN-γ (cut-off values>0, ≥6 and ≥10 spot forming cells/well (SFCs/well)) and CD4 cell count (cut-off values<250 and <350 cells/μL) were evaluated for sensitivity and specificity using a time dependent receiver operating characteristic (ROC) curve and positive predictive value (PPV) using Kaplan Meier method for future TB within one year postpartum.
Of 327 women, 9 developed TB within one year postpartum (Incidence rate (IR): 3.5/100 person-years of follow-up (pyfu); 95% confidence interval: 1.6–6.7/100 pyfu). IFN-γ≥6 SFCs/well was associated with an optimal trade-off between sensitivity (78%) and specificity (55%) and PPV of 5.9%. In women with CD4<250 cells/μL, sensitivity and specificity of IFN-γ≥6 SFCs/well were 89% and 63%, respectively and PPV was 19.2%.
Among HIV-1 infected women, IFN-γ response (≥6 SFCs/well) during pregnancy lacked high positive predictive value for postpartum TB but had higher sensitivity and positive predictive value among immunosuppressed women (CD4<250 cells/μL).
TB IGRA; Predictive value; Sensitivity; Specificity; HIV-infected women
HIV testing male partners of pregnant women may decrease HIV transmission to women and promote uptake of prevention of mother-to-child HIV transmission (PMTCT) interventions. However, it has been difficult to access male partners in antenatal care (ANC) clinics. We hypothesized that home visits to offer HIV testing to partners of women attending ANC would increase partner HIV testing.
Women attending their first ANC were enrolled, interviewed using smartphone audio-computer assisted self-interviews and randomized to home visits or written invitations for male partners to come to clinic, if they were married or cohabiting, unaccompanied by partners and had no prior couple HIV counseling and testing (CHCT). Enrolled men were offered CHCT (HIV testing and mutual disclosure). Prevalence of CHCT, male HIV seropositivity, couple serodiscordance, and intimate partner violence, reported as physical threat from partner, were compared at 6 weeks.
Among 495 women screened, 312 were eligible, and 300 randomized to clinic-based or home-based CHCT. Median age was 22 years (interquartile range 20, 26), and 87% were monogamous. CHCT was significantly higher in home-visit than clinic-invitation arm (n=128, 85% vs n=54, 36%; p<0.001). Home-arm identified more HIV-seropositive men (12.0 % vs 8.0 %; p= 0.248) and more HIV-discordant couples (14.7% vs 4.7%; p=0.003). There was no difference in intimate partner violence.
Home visits of pregnant women were safe and resulted in more male partner testing and mutual disclosure of HIV status. This strategy could facilitate prevention of maternal HIV acquisition, improve PMTCT uptake, and increase male HIV diagnosis.
male partner; couple HIV testing; pregnancy
In human immunodeficiency virus–infected women, cervical cytomegalovirus (CMV) reactivation during pregnancy was correlated with higher CMV levels in breast milk. Low maternal CD4 count and high CMV levels in breast milk were independently associated with infant CMV infection.
Background. Cytomegalovirus (CMV) infection is associated with adverse outcomes in human immunodeficiency virus (HIV)–exposed infants. Determinants of vertical CMV transmission in the setting of maternal HIV-1 infection are not well-defined.
Methods. CMV and HIV-1 levels were measured in plasma, cervical secretions, and breast milk of 147 HIV-1–infected women to define correlates of maternal CMV replication and infant CMV acquisition.
Results. Although few women had detectable CMV in plasma (4.8%), the majority had detectable CMV DNA in cervical secretions (66%) and breast milk (99%). There was a strong association between cervical CMV detection during pregnancy and later breast milk levels (β = 0.47; P = .005). Plasma HIV-1 level and CD4 counts were associated with CMV in the cervix and breast milk. However HIV-1 levels within the cervix and breast milk were not associated with CMV within these compartments. Maternal breast milk CMV levels (hazard ratio [HR], 1.4; P = .003) and maternal CD4 < 450 cells/mm3 (HR, 1.8; P = .008) were independently associated with infant CMV acquisition; each log10 increase in breast milk CMV was associated with a 40% increase in infant infection. The breast milk CMV level required to attain a 50% probability of CMV transmission increased with higher maternal CD4 counts, increasing from 3.55 log10 CMV DNA copies/mL at a CD4 count of 350 cells/mm3 to 5.50 log10 CMV DNA copies/mL at a CD4 count of 1000 cells/mm3.
Conclusions. Breast milk CMV levels and maternal CD4 count are major determinants of CMV transmission in the setting of maternal HIV-1. Maternal immune reconstitution or lowering breast milk CMV levels may reduce vertical CMV transmission.
cytomegalovirus; human immunodeficiency virus; neonates; opportunistic infection; compartmentalization
HIV case-finding and linkage to care are critical for control of HIV transmission. In Kenya, >50% of seropositive individuals are unaware of their status. Assisted partner notification is a public health strategy that provides HIV testing to individuals with sexual exposure to HIV and are at risk of infection and disease. This parallel, cluster-randomized controlled trial will evaluate the effectiveness, cost-effectiveness, and feasibility of implementing HIV assisted partner notification services at HIV testing sites (clusters) in Kenya.
Eighteen sites were selected among health facilities in Kenya with well-established, high-volume HIV testing programs, to reflect diverse communities and health-care settings. Restricted randomization was used to balance site characteristics between study arms (n = 9 per arm). Sixty individuals testing HIV positive (‘index partners’) will be enrolled per site (inclusion criteria: ≥18 years, positive HIV test at a study site, willing to disclose sexual partners, and never enrolled for HIV care; exclusion criteria: pregnancy or high risk of intimate partner violence). Index partners provide names and contact information for all sexual partners in the past 3 years. At intervention sites, study staff immediately contact sexual partners to notify them of exposure, offer HIV testing, and link to care if HIV seropositive. At control sites, passive partner referral is performed according to national guidelines, and assisted partner notification is delayed by 6 weeks. Primary outcomes, assessed 6 weeks after index partner enrollment and analyzed at the cluster level, are the number of partners accepting HIV testing and number of HIV infections diagnosed and linked to care per index partner. Secondary outcomes are the incremental cost-effectiveness of partner notification and the costs of identifying >1 partner per index case. Participants are closely monitored for adverse outcomes, particularly intimate partner violence. The study is unblinded due to practical limitations.
This rigorously designed trial will inform policy decisions regarding implementation of HIV partner notification services in Kenya, with possible application to other parts of sub-Saharan Africa. Examination of effectiveness and cost-effectiveness in diverse settings will enable targeted application and define best practices.
HIV; Assisted partner notification; Contact tracing; Linkage to care; HIV testing and counselling; Health advisors; Sub-Saharan Africa; 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.
HIV-1 serodiscordant couples; Relationship dissolution; Separation; HIV-1 transmission; Poverty; Women
Despite evidence that international clinical electives can be educationally and professionally beneficial to both visiting and in-country trainees, these opportunities remain challenging for American residents to participate in abroad. Additionally, even when logistically possible, they are often poorly structured. The Universities of Washington (UW) and Nairobi (UoN) have enjoyed a long-standing research collaboration, which recently expanded into the UoN Medical Education Partnership Initiative (MEPI). Based on MEPI in Kenya, the Clinical Education Partnership Initiative (CEPI) is a new educational exchange program between UoN and UW. CEPI allows UW residents to partner with Kenyan trainees in clinical care and teaching activities at Naivasha District Hospital (NDH), one of UoN’s MEPI training sites in Kenya.
UW and UoN faculty collaborated to create a curriculum and structure for the program. A Chief Resident from the UW Department of Medicine coordinated the program at NDH. From August 2012 through April 2014, 32 UW participants from 5 medical specialties spent between 4 and 12 weeks working in NDH. In addition to clinical duties, all took part in formal and informal educational activities. Before and after their rotations, UW residents completed surveys evaluating clinical competencies and cross-cultural educational and research skills. Kenyan trainees also completed surveys after working with UW residents for three months.
UW trainees reported a significant increase in exposure to various tropical and other diseases, an increased sense of self-reliance, particularly in a resource-limited setting, and an improved understanding of how social and cultural factors can affect health. Kenyan trainees reported both an increase in clinical skills and confidence, and an appreciation for learning a different approach to patient care and professionalism.
After participating in CEPI, both Kenyan and US trainees noted improvement in their clinical knowledge and skills and a broader understanding of what it means to be clinicians. Through structured partnerships between institutions, educational exchange that benefits both parties is possible.
Electronic supplementary material
The online version of this article (doi:10.1186/s12909-014-0246-5) contains supplementary material, which is available to authorized users.
International; Clinical rotation; Medical education; Residents; Kenya
Background. Daily suppressive therapy with valacyclovir reduces risk of sexual transmission of herpes simplex virus type 2 (HSV-2) in HSV-2–serodiscordant heterosexual couples by 48%. Whether suppressive therapy reduces HSV-2 transmission from persons coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) is unknown.
Methods. Within a randomized trial of daily acyclovir 400 mg twice daily in African HIV-1 serodiscordant couples, in which the HIV-1–infected partner was HSV-2 seropositive, we identified partnerships in which HIV-1–susceptible partners were HSV-2 seronegative to estimate the effect of acyclovir on risk of HSV-2 transmission.
Results. We randomly assigned 911 HSV-2/HIV-1–serodiscordant couples to daily receipt of acyclovir or placebo. We observed 68 HSV-2 seroconversions, 40 and 28 in acyclovir and placebo groups, respectively (HSV-2 incidence, 5.1 cases per 100 person-years; hazard ratio [HR], 1.35 [95% confidence interval, .83–2.20]; P = .22). Among HSV-2–susceptible women, vaginal drying practices (adjusted HR, 44.35; P = .004) and unprotected sex (adjusted HR, 9.91; P = .002) were significant risk factors for HSV-2 acquisition; having more children was protective (adjusted HR, 0.47 per additional child; P = .012). Among HSV-2–susceptible men, only age ≤30 years was associated with increased risk of HSV-2 acquisition (P = .016).
Conclusions. Treatment of African HSV-2/HIV-1–infected persons with daily suppressive acyclovir did not decrease risk of HSV-2 transmission to susceptible partners. More-effective prevention strategies to reduce HSV-2 transmission from HIV-1–infected persons are needed.
HSV-2; HIV-1; acyclovir; transmission; serodiscordant couples; Africa
A 34-y-old man presented to Naivasha District Hospital (NDH) in Naivasha Town, Kenya, with near-complete below-knee amputation and hemorrhage after a hippopotamus attack. Residents from the University of Washington (UW), Departments of Surgery, Anesthesia, and Medicine, were rotating at NDH with the Clinical Education Partnership Initiative, a joint venture of UW and University of Nairobi. These providers met the patient in the operating theater. The leg was mangled with severely traumatized soft tissues and tibia–fibula fractures. The visiting UW Surgery resident (R3) and an NDH medical officer (second-year house officer) performed emergency below-knee completion amputation—the first time either had performed this operation. The three major vessel groups were identified and ligated. Sufficient gastrocnemius and soleus were preserved for future stump construction. The wound was washed out, packed with betadine-soaked gauze, and wrapped in an elasticized bandage. Broad-spectrum antibiotics were initiated. Unfortunately, the patient suffered infection and was revised above the knee. After a prolonged course, the patient recovered well and was discharged home. NDH house officers and UW trainees collaborated successfully in an emergency and conducted the postoperative care of a patient with a serious and challenging injury. Their experience highlights the importance of preparedness, command of surgical basics, humility, learning from mistakes, the expertise of others, a digitally connected surgical community, and the role of surgery in global health. These lessons will be increasingly pertinent as surgical training programs create opportunities for their residents to work in developing countries; many of these lessons are equally applicable to surgical practice in the developed world.
Surgical education; Global health; Traumatic amputation; Surgical training; Preparedness
Background. The synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) is well known, but lack of knowledge about the epidemiology of HSV-2 acquisition in HIV-1-discordant couples hampers development of HSV-2 prevention interventions that could reduce HIV-1 transmission.
Methods. HIV-1-discordant couples were enrolled in Nairobi, Kenya, and followed for up to 2 years. HSV-2 status was determined using HerpeSelect HSV-2 ELISA. Correlates of prevalence and incidence were assessed.
Results. Of 469 HIV-1-discordant couples, at baseline, 353 (75.3%) were affected by HSV-2, of which 189 (53.5%) were concordantly HSV-2 seropositive and 164 (46.5%) were HSV-2-discordant. Prevalence was lowest among HIV-1-uninfected men (39.9%) compared to HIV-1-infected women (64.8%), HIV-1-infected men (66.7%), and HIV-1-uninfected women (68.5%). During follow-up, HSV-2 seroincidence was 14.9 per 100 person-years. Incidence was 1.6-fold higher among females compared to males (95% confidence interval [CI], 1.00–2.48) and 2.5-fold higher in HIV-1-infected compared to uninfected women (95% CI, 1.12–5.74). At least 30% of incident HSV-2 infections originated from an outside partner.
Conclusions. The high HSV-2 prevalence and incidence in HIV-1-discordant couples in sub-Saharan Africa suggest HSV-2 treatment and prevention could be an effective targeted strategy to reduce HSV-2 and HIV-1 transmission in this high-risk population.
HSV-2; herpes; HIV; discordant; serodiscordant; couples; genital ulcer disease; Kenya; incidence; prevalence; transmission; prevention; Africa; antiviral; seroconvert; ELISA
Disclosure to HIV-infected children regarding their diagnosis is important as expanding numbers of HIV-infected children attain adolescence and may become sexually active. In order to define correlates of pediatric disclosure and facilitate development of models for disclosure, we conducted a cross-sectional survey of primary caregivers of HIV-1 infected children aged 6 to 16 years attending a pediatric HIV treatment program in Nairobi, Kenya. We conducted focus group discussions with a subset of caregivers to further refine perceptions of disclosure.
Among 271 caregiver/child dyads in the cross-sectional survey, median child age was 9 years (IQR: 7, 12 years). Although 79% of caregivers believed children should know their HIV status, the prevalence of disclosure to the child was only 19%. Disclosure had been done primarily by health workers (52%) and caregivers (33%). Caregivers reported that 5 of the 52 (10%) who knew their status were accidentally disclosed to. Caregivers of older children (13 vs. 8 years; p<0.001), who were HIV-infected and had disclosed their own HIV status to the child (36% vs. 4%; p=0.003), or who traveled frequently (29% vs. 16%, p=0.03) were more likely to have disclosed. Children who had been recently hospitalized (25% vs. 44%, p=0.03) were less likely to know their status and caregivers with HIV were less likely to have disclosed (p=0.03). Reasons for disclosure included medication adherence, curiosity or illness while reasons for non-disclosure included age and fear of inadvertent disclosure.
Our study found that disclosure rates in this Kenyan setting are lower than observed rates in the United States and Europe but consistent with rates from other resource-limited settings. Given these low rates of disclosure and the potential benefits of disclosure, strategies promoting health worker trainings and caregiver support systems for disclosure may benefit children with HIV.
disclosure; pediatric; HIV; stigma; adherence
There are limited data on the impact of cesarean section delivery on HIV-1 infected women in Sub-Saharan Africa. The purpose of this study was to assess the effect of mode of delivery on HIV-1 disease progression and postpartum mortality in a Kenyan cohort.
A prospective cohort study was conducted in Nairobi, Kenya from 2000–2005. We determined changes in CD4+ counts, HIV-1 RNA levels and mortality during the first year postpartum between HIV-1 infected women who underwent vaginal delivery (VD), non-scheduled cesarean section (NSCS) and scheduled cesarean section (SCS) and received short-course zidovudine. Loess curves and multivariate linear mixed effects models were used to compare longitudinal changes in maternal HIV-1 RNA and CD4+ counts by mode of delivery. Kaplan Meier curves, the log rank test, and Cox proportional hazards regression were used to assess difference in mortality.
Of 501 women, 405 delivered by VD, 74 delivered by NSCS and 22 by SCS. Baseline characteristics were similar between the VD and NSCS groups. Baseline antenatal CD4+ counts were lowest and HIV-1 RNA levels highest in the NSCS group but HIV-1 RNA levels were similar between groups at delivery. The rate of decline in CD4+ cells and rate of increase in HIV-1 RNA did not differ between groups. After adjusting for confounders, women who underwent NSCS had a 3.39-fold (95% CI 1.11, 10.35, P = 0.03) higher risk of mortality in the first year postpartum compared to women with VD.
Non-scheduled cesarean section was an independent risk factor for postpartum mortality in HIV-1 positive Kenyan women. The cause of death was predominantly due to HIV-1 related infections, and not direct maternal deaths, however, this was not mirrored by differential changes in HIV-1 progression markers between the groups.
HIV; Mode of delivery; Cesarean section; HIV-1 disease progression; Maternal mortality
Early infant HIV-1 diagnosis and treatment substantially improve survival. Where virologic HIV-1 testing is unavailable, Integrated Management of Childhood Illness (IMCI) clinical algorithms may be used for infant HIV-1 screening. We evaluated the performance of the 2008 WHO IMCI HIV algorithm in a cohort of HIV-exposed Kenyan infants.
From 1999–2003, 444 infants had monthly clinical assessments and quarterly virologic HIV-1 testing. Using archived clinical data, IMCI sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using virologic testing as a gold standard. Linear regression and survival analyses were used to determine the effect of age on IMCI performance and timing of diagnosis.
Overall IMCI sensitivity, specificity, PPV, and NPV value were 58%, 87%, 52%, and 90%, respectively. Sensitivity (1.4%) and PPV (14%) were lowest at 1 month of age, when 81% of HIV-infections already had occurred. Sensitivity increased with age (p<0.0001), but remained low throughout infancy (range=1.4–35%). Specificity (range=97–100%) was high at each time point and was not associated with age. Fifty-eight percent of HIV-1 infected infants (50/86) were eventually diagnosed by IMCI, and use of IMCI was estimated to delay diagnosis in HIV-infected infants by a median of 5.9 months (p<0.0001).
IMCI had low sensitivity during the first month of life, when the majority of HIV-1 infections had already occurred, and initiation of treatment is most critical. Although sensitivity increased with age, the substantial delay in HIV-1 diagnosis using IMCI limits its utility in early infant HIV-1 diagnosis.
IMCI; HIV; infant; Africa; clinical algorithm; pediatric
This analysis compared the frequency of persistent Trichomonas vaginalis (TV) among HIV-seropositive and HIV-seronegative women.
Data were obtained from women enrolled in an open cohort study of sex workers in Kenya. Participants were examined monthly, and those diagnosed with TV by saline microscopy were treated with single-dose 2g oral metronidazole. All women on antiretroviral therapy (ART) used nevirapine-based regimens. Generalized estimating equations with a logit link were used to compare the frequency of persistent TV (defined as the presence of motile trichomonads by saline microscopy at the next exam visit within 60 days) by HIV status.
Three-hundred and sixty participants contributed 570 infections to the analysis (282 HIV-seropositive and 288 HIV-seronegative). There were 42 (15%) persistent infections among HIV-seropositive participants versus 35 (12%) among HIV-seronegative participants (adjusted odds ratio [aOR]=1.14; 95% confidence interval [CI] (0.70, 1.87)). Persistent TV was highest among HIV-seropositive women using ART (21/64 [33%]) compared to HIV-seropositive women not using ART (21/217 [10%]). Concurrent bacterial vaginosis (BV) at TV diagnosis was associated with an increased likelihood of persistent TV (aOR=1.90; 95% CI 1.16, 3.09).
The frequency of persistent TV infection following treatment with single-dose 2g oral metronidazole was similar by HIV status. Alternative regimens, including multi-day antibiotic treatment, may be necessary to improve cure rates for women using nevirapine-based ART and women with TV and concurrent BV.
Trichomonas vaginalis; metronidazole; efficacy; persistence; HIV infection; nevirapine; antiretroviral therapy
Despite significant increases in global health investment and the availability of low-cost, efficacious interventions to prevent mother-to-child HIV transmission (pMTCT) in low- and middle-income countries with high HIV burden, the translation of scientific advances into effective delivery strategies has been slow, uneven and incomplete. As a result, pediatric HIV infection remains largely uncontrolled. A five-step, facility-level systems analysis and improvement intervention (SAIA) was designed to maximize effectiveness of pMTCT service provision by improving understanding of inefficiencies (step one: cascade analysis), guiding identification and prioritization of low-cost workflow modifications (step two: value stream mapping), and iteratively testing and redesigning these modifications (steps three through five). This protocol describes the SAIA intervention and methods to evaluate the intervention’s impact on reducing drop-offs along the pMTCT cascade.
This study employs a two-arm, longitudinal cluster randomized trial design. The unit of randomization is the health facility. A total of 90 facilities were identified in Côte d’Ivoire, Kenya and Mozambique (30 per country). A subset was randomly selected and assigned to intervention and comparison arms, stratified by country and service volume, resulting in 18 intervention and 18 comparison facilities across all three countries, with six intervention and six comparison facilities per country. The SAIA intervention will be implemented for six months in the 18 intervention facilities. Primary trial outcomes are designed to assess improvements in the pMTCT service cascade, and include the percentage of pregnant women being tested for HIV at the first antenatal care visit, the percentage of HIV-infected pregnant women receiving adequate prophylaxis or combination antiretroviral therapy in pregnancy, and the percentage of newborns exposed to HIV in pregnancy receiving an HIV diagnosis eight weeks postpartum. The Consolidated Framework for Implementation Research (CFIR) will guide collection and analysis of qualitative data on implementation process.
This study is a pragmatic trial that has the potential benefit of improving maternal and infant outcomes by reducing drop-offs along the pMTCT cascade. The SAIA intervention is designed to provide simple tools to guide decision-making for pMTCT program staff at the facility level, and to identify low cost, contextually appropriate pMTCT improvement strategies.
Systems analysis; Quality improvement; pmtct; Value stream mapping; Cascade analysis; Cluster randomized trial; Industrial engineering; Implementation science; Mozambique; Kenya; Côte d’Ivoire
Recent data suggest that infection with human immunodeficiency virus type 1 (HIV-1) subtype C results in prolonged high-level viremia (>5 log10 copies/mL) during early infection. We examined the relationship between HIV-1 subtype and plasma viremia among 153 African seroconverters. Mean setpoint viral loads were similar for C and non-C subtypes: 4.36 vs 4.42 log10 copies/mL (P = .61). The proportion of subtype C–infected participants with viral loads >5 log10 copies/mL was not greater than the proportion for those with non-C infection. Our data do not support the hypothesis that higher early viral load accounts for the rapid spread of HIV-1 subtype C in southern Africa.
HIV-1; group M subtype; plasma viral load; early infection; Africa