HIV-exposed uninfected (HEU) infants are a growing population in sub-Saharan Africa, with higher morbidity and mortality than HIV-unexposed infants. HEU infants may experience increased morbidity due to breastfeeding avoidance.
We sought to describe the burden and identify predictors of hospitalization among HEU infants in the first year of life.
Using a retrospective cohort of HIV-infected mothers and their HEU infants in Nairobi, Kenya, we identified infants who were HIV-uninfected at birth and were followed monthly until last negative HIV test, death, loss to follow-up or study exit at one year of age. Incidence, timing and reason for hospitalization was assessed overall as well as stratified by feeding method. Predictors of first infectious disease hospitalization were identified using competing risk regression, with HIV acquisition and death as competing risks.
Among 388 infants, 113 hospitalizations were reported [35/100 infant-years, 95% confidence interval (CI) 29–42]. Ninety hospitalizations were due to one or more infectious diseases [26/100 infant-years, 95%CI 21–32], primarily pneumonia (n=40), gastroenteritis (n=17) and sepsis (n=14). Breastfeeding was associated with decreased risk of infectious disease hospitalization [SHR=0.39 (95%CI 0.24–0.64)], as was time-updated nutritional status [SHR=0.73 (95%CI 0.61–0.89)]. Incidence of infectious disease hospitalization among formula-fed infants was 51/100 child-years (95%CI 37–70) compared to 19/100 child-years (95%CI 14–25) among breastfed infants.
Among HEU infants, breastfeeding and nutritional status were associated with reduced hospitalization during the first year of life.
Despite advances in treatment of people living with HIV, morbidity and mortality remains unacceptably high in sub-Saharan Africa, largely due to parallel epidemics of poverty and food insecurity.
We conducted a pilot cluster randomized controlled trial (RCT) of a multisectoral agricultural and microfinance intervention (entitled Shamba Maisha) designed to improve food security, household wealth, HIV clinical outcomes and women’s empowerment. The intervention was carried out at two HIV clinics in Kenya, one randomized to the intervention arm and one to the control arm. HIV-infected patients >18 years, on antiretroviral therapy, with moderate/severe food insecurity and/or body mass index (BMI) <18.5, and access to land and surface water were eligible for enrollment. The intervention included: 1) a microfinance loan (~$150) to purchase the farming commodities, 2) a micro-irrigation pump, seeds, and fertilizer, and 3) trainings in sustainable agricultural practices and financial literacy. Enrollment of 140 participants took four months, and the screening-to-enrollment ratio was similar between arms. We followed participants for 12 months and conducted structured questionnaires. We also conducted a process evaluation with participants and stakeholders 3–5 months after study start and at study end.
Baseline results revealed that participants at the two sites were similar in age, gender and marital status. A greater proportion of participants at the intervention site had a low BMI in comparison to participants at the control site (18% vs. 7%, p = 0.054). While median CD4 count was similar between arms, a greater proportion of participants enrolled at the intervention arm had a detectable HIV viral load compared with control participants (49% vs. 28%, respectively, p < 0.010). Process evaluation findings suggested that Shamba Maisha had high acceptability in recruitment, delivered strong agricultural and financial training, and led to labor saving due to use of the water pump. Implementation challenges included participant concerns about repaying loans, agricultural challenges due to weather patterns, and a challenging partnership with the microfinance institution. We expect the results from this pilot study to provide useful data on the impacts of livelihood interventions and will help in the design of a definitive cluster RCT.
This trial is registered at ClinicalTrials.gov, NCT01548599.
Electronic supplementary material
The online version of this article (doi:10.1186/s40064-015-0886-x) contains supplementary material, which is available to authorized users.
HIV; Food insecurity; Microfinance; Agriculture; Livelihoods; Intervention
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
Humoral immune responses play a pivotal role in naturally acquired immunity to malaria. Understanding which humoral responses are impaired among individuals at higher risk for malaria may improve our understanding of malaria immune control and contribute to vaccine development.
We compared humoral responses with 483 Plasmodium falciparum antigens between adults in, Kisumu (high, year-long malaria transmission leading to partial immunity), and adults in Kisii (low, seasonal malaria transmission). Then within each site, we compared malaria-specific humoral responses between those at higher risk for malaria (CD4+ ≤ 500) and those at lower risk for malaria (CD4+>500). A protein microarray chip containing 483 P. falciparum antigens and 71 HIV antigens was used. Benjamini–Hochberg adjustments were made to control for multiple comparisons.
Fifty-seven antigens including CSP, MSP1, LSA1 and AMA1 were identified as significantly more reactive in Kisumu than in Kisii. Ten of these antigens had been identified as protective in an earlier study. CD4+ T-cell count did not significantly impact humoral responses.
Protein microarrays are a useful method to screen multiple humoral responses simultaneously. This study provides useful clues for potential vaccine candidates. Modest decreases in CD4 counts may not significantly impact malaria-specific humoral immunity.
HIV-1; Humoral Immunity; Malaria; Vaccine
There is conflicting evidence regarding the effects of breast-feeding on maternal mortality from human immunodeficiency virus type 1 (HIV-1) infection, and little is known about the effects of breast-feeding on markers of HIV-1 disease progression.
HIV-1–seropositive women were enrolled during pregnancy and received short-course zidovudine. HIV-1 RNA levels and CD4 cell counts were determined at baseline and at months 1, 3, 6, 12, 18, and 24 postpartum and were compared between breast-feeding and formula-feeding mothers.
Of 296 women, 98 formula fed and 198 breast-fed. At baseline, formula-feeding women had a higher education level and prevalence of HIV-1–related illness than did breast-feeding women; however, the groups did not differ with respect to CD4 cell counts and HIV-1 RNA levels. Between months 1 and 24 postpartum, CD4 cell counts decreased 3.9 cells/µL/month (P< .001), HIV-1 RNA levels increased 0.005 log10 copies/mL/month (P = .03), and body mass index (BMI) decreased 0.03 kg/m2/month (P< .001). The rate of CD4 cell count decline was higher in breast-feeding mothers (7.2 cells/µL/month) than in mothers who never breast-fed (4.0 cells/µL/month) (P = .01). BMI decreased more rapidly in breast-feeding women (P = .04), whereas HIV-1 RNA levels and mortality did not differ significantly between breast-feeding and formula-feeding women.
Breast-feeding was associated with significant decreases in CD4 cell counts and BMI. HIV-1 RNA levels and mortality were not increased, suggesting a limited adverse impact of breast-feeding in mothers receiving extended care for HIV-1 infection.
Pediatric human immunodeficiency virus type 1 (HIV-1) infection follows a bimodal clinical course with rapid progression in 10 – 45% of children before the age of 2 years and slower progression in the remainder. A prospective observational study was undertaken to determine predictors of mortality in HIV-1-infected African infants during the first 2 years of life.
Infants in a perinatal cohort identified to be HIV-1-infected by DNA PCR were followed monthly to 1 year, then quarterly to 2 years or death.
Among 62 HIV-1-infected infants, infection occurred by the age of 1 month in 56 (90%) infants, and 32 (52%) died at median age of 6.2 months. All infant deaths were caused by infectious diseases, most frequently pneumonia (75%) and diarrhea (41%). Univariate predictors of infant mortality included maternal CD4 count <200 cells/μl [hazard ratio (HR), 3.4; P = 0.008], maternal anemia (HR = 3.7; P = 0.005), delivery complications (HR = 2.7; P = 0.01), low birth weight (HR = 4.1; P = 0.001), weight, length and head circumference ≤5th percentile at age 1 month (HR = 3.7, P = 0.003; HR = 5.8, P < 0.001; and HR = 10.4, P < 0.001, respectively), formula-feeding (HR = 4.0; P = 0.01), infant CD4% ≤15% (HR = 5.5; P = 0.01), infant CD4 count <750 (HR = 9.7; P = 0.006) and maternal death (HR = 2.9, P = 0.05). In multivariate analysis, maternal CD4 count <200 (HR = 2.7; P = 0.03) and delivery complications (HR = 3.4; P = 0.005) were independently associated with infant mortality.
Advanced maternal HIV disease, maternal anemia, delivery complications, early growth faltering, formula-feeding and low infant CD4 were predictors of early mortality in African HIV-1-infected infants. In resource-poor settings, these predictors may be useful for early identification and treatment of high risk infants.
Human immunodeficiency virus type 1; disease progression; mortality; predictors
To assess the immediate and longer-term effects of the use of hormonal contraception on the progression of HIV-1 disease in postpartum women.
A prospective cohort study.
Information on contraceptive use, breastfeeding and intercurrent illnesses was obtained from HIV-infected postpartum Kenyan women monthly in the first year postpartum and quarterly in the second year. Blood was collected for T-cell subset analyses and HIV-1-RNA levels at months 1, 3, 6, 9, 12, 18, and 24 postpartum. The immediate effect of the initiation of oral contraceptive pills (OCP) and depot medroxyprogesterone acetate (DMPA) was assessed by comparing the change in the HIV-1-RNA plasma viral load and CD4 T-cell counts among women remaining off these contraceptive methods with those initiating them. The longer-term effects of OCP and DMPA on disease progression were assessed using Loess curves and linear mixed effects models to compare changes over the first 24 months postpartum in these same disease progression markers.
There were no significant immediate or longer-term effects of the use of OCP or DMPA on HIV-1-RNA plasma viral loads and CD4 T-cell counts in this cohort of HIV-infected postpartum Kenyan women.
Comprehensive contraceptive counselling for HIV-1-infected women requires an understanding of the effects of various contraceptive methods on HIV-1 disease progression. In this study, hormonal contraception reassuringly had no immediate or longer-term effects on the rate of disease progression in chronically HIV-1-infected postpartum women. This highly effective family planning method may provide a useful and safe option for the prevention of mother-to-child transmission of HIV-1.
Contraception; depot medroxyprogesterone acetate; HIV-1; oral contraceptive pill; postpartum; progression
Human leukocyte antigen (HLA) molecules regulate the cellular immune system and may be determinants of infant susceptibility to human immunodeficiency virus type 1 (HIV-1) infection. Molecular HLA typing for class I alleles was performed on infants followed in a Kenyan perinatal cohort. Early HIV-1 infection status was defined as infection occurring at birth or month 1, while late infection via breast milk was defined as first detection of HIV-1 after 1 month of age. Likelihood ratio tests based on a proportional hazards model adjusting for maternal CD4 T cell count and HIV-1 viral load at 32 weeks of gestation were used to test associations between infant allelic variation and incident HIV-1 infection. Among 433 infants, 76 (18%) were HIV-1 infected during 12 months of follow-up. HLA B*18 was associated with a significantly lower risk of early HIV-1 transmission [relative risk (RR) = 0.26; 95% confidence interval (CI) 0.04–0.82], and none of the 24 breastfeeding infants expressing HLA B*18 who were uninfected at month 1 acquired HIV-1 late via breast milk. We observed a trend toward increased early HIV-1 acquisition for infants presenting HLA A*29 (RR = 2.0; 95% CI 1.0–3.8) and increased late HIV-1 acquisition via breast milk for both Cw*07 and Cw*08 (RR = 4.0; 95% CI 1.0–17.8 and RR = 7.2; 95% CI 1.2–37.3, respectively). HLA B*18 may protect breast-feeding infants against both early and late HIV-1 acquisition, a finding that could have implications for the design and monitoring of HIV-1 vaccines targeting cellular immune responses against HIV-1.
Much of the burden of morbidity affecting women of childbearing age in sub-Saharan Africa occurs in the context of HIV-1 infection. Understanding patterns of illness and determinants of disease in HIV-1–infected mothers may guide effective interventions to improve maternal health in this setting.
We describe the incidence and cofactors of comorbidities affecting peripartum and postpartum HIV-1–infected women in Kenya. Women were evaluated by clinical examination and standardized questionnaires during pregnancy and for up to 2 years after delivery.
Five hundred thirty-five women were enrolled in the cohort (median CD4 count of 433 cells/mm3) and accrued 7736 person-months of follow-up. During 1-year follow-up, the incidence of upper respiratory tract infections was 161 per 100 person-years, incidence of pneumonia was 33 per 100 person-years, incidence of tuberculosis (TB) was 11 per 100 person-years, and incidence of diarrhea was 63 per 100 person-years. Immunosuppression and HIV-1 RNA levels were predictive for pneumonia, oral thrush, and TB but not for diarrhea; CD4 counts <200 cells/mm3 were associated with pneumonia (relative risk [RR] = 2.87, 95% confidence interval [CI]: 1.71 to 4.83), TB (RR = 7.14, 95% CI: 2.93 to 17.40) and thrush. The risk of diarrhea was significantly associated with crowding (RR = 1.86, 95% CI: 1.19 to 2.92) and breast-feeding (RR = 1.71, 95% CI: 1.19 to 2.44). Less than 10% of women reported hospitalization during 2-year follow-up; mortality risk in the cohort was 1.9% and 4.8% for 1 and 2 years, respectively.
Mothers with HIV-1, although generally healthy, have substantial morbidity as a result of common infections, some of which are predicted by immune status or by socioeconomic factors. Enhanced attention to maternal health is increasingly important as HIV-1–infected mothers transition from programs targeting the prevention of mother-to-child transmission to HIV care clinics.
HIV/AIDS; HIV-1 progression; maternal health; morbidity; postpartum; pregnancy; prevention of mother-to-child transmission; women
We evaluated the prognostic utility of interferon-gamma release assays (IGRAs) for active tuberculosis (TB) and mortality in Kenyan HIV-1 infected women and their infants.
Prevalence and correlates of Mycobacterium tuberculosis-specific T-SPOT.TB IGRA positivity were determined during pregnancy in a historical cohort of HIV-1 infected women. Hazard ratios, adjusted for baseline maternal CD4 count (aHRCD4) were calculated for associations between IGRA positivity and risk of active TB and mortality over 2-year postpartum follow-up in women and their infants.
Of 333 women tested, 52 (15.6%) had indeterminate IGRAs. Of the remaining 281 women, 120 (42.7%) had positive IGRAs, which were associated with a 4.5-fold increased risk of active TB [aHRCD4: 4.5; 95% confidence interval (CI): 1.1–18.0; p=0.03]. Among immunosuppresed women (CD4<250 cell/mm3), positive IGRAs were associated with increased risk of maternal mortality (aHRCD4: 3.5; 95% CI: 1.02–12.1; p=0.045), maternal active TB or mortality (aHRCD4: 5.2; 95% CI: 1.7–15.6; p=0.004) and infant active TB or mortality, overall (aHRCD4: 3.0; 95% CI: 1.0–8.9; p= 0.05) and in HIV-1 exposed uninfected infants (aHRCD4: 7.3; 95% CI: 1.6–33.5; p =0.01).
Positive IGRAs in HIV-1 infected pregnant women were associated with postpartum active TB and mortality in mothers and their infants.
Latent tuberculosis infection; HIV-1; women; infants; T-SPOT.TB; IGRA
Background. We evaluated the prognostic usefulness of interferon γ release assays (IGRAs) for active tuberculosis and mortality in Kenyan human immunodeficiency virus type 1 (HIV-1)-infected women and their infants.
Methods. Prevalence and correlates of Mycobacterium tuberculosis-specific T-SPOT.TB IGRA positivity were determined during pregnancy in a historical cohort of HIV-1-infected women. Hazard ratios, adjusted for baseline maternal CD4 cell count (aHRCD4), were calculated for associations between IGRA positivity and risk of active tuberculosis and mortality over 2-year postpartum follow-up among women and their infants.
Results. Of 333 women tested, 52 (15.6%) had indeterminate IGRA results. Of the remaining 281 women, 120 (42.7%) had positive IGRA results, which were associated with a 4.5-fold increased risk of active tuberculosis (aHRCD4, 4.5; 95% confidence interval [CI], 1.1–18.0; P = .030). For immunosuppressed women (CD4 cell count, <250 cells/µL), positive IGRA results were associated with increased risk of maternal mortality (aHRCD4, 3.5; 95% CI, 1.02–12.1; ), maternal active tuberculosis or mortality (aHRCD4
P = .045 , 5.2; 95% CI, 1.7–15.6; P = .004), and infant active tuberculosis or mortality overall (aHRCD4, 3.0; 95% CI, 1.0–8.9; P = .05) and among HIV-1-exposed uninfected infants (aHRCD4, 7.3; 95% CI, 1.6–33.5; P = .01).
Conclusions. Positive IGRA results for HIV-1-infected pregnant women were associated with postpartum active tuberculosis and mortality among mothers and their infants.
As prevention of mother-to-child transmission of HIV (PMTCT) programs and HIV treatment programs rapidly expand in parallel, it is important to determine factors that influence the transition of HIV-infected women from maternal to continuing care.
This study aimed to determine rates and co-factors of accessing HIV care by HIV-infected women exiting maternal care. A cross-sectional survey of women who had participated in a PMTCT research study and were referred to care programs in Nairobi, Kenya was conducted.
A median of 17 months following referral, women were located by peer counselors and interviewed to determine whether they accessed HIV care and what influenced their care decisions. Fisher’s exact test was used to assess the association between client characteristics and access to care.
Peer counselors traced 195 (82%) residences, where they located 116 (59%) participants who provided information on care. Since exit, 50% of participants had changed residence, and 74% reported going to the referral HIV program. Reasons for not accessing care included lack of money, confidentiality, and dislike of the facility. Women who did not access care were less likely to have informed their partner of the referral (p=0.001), and were less likely believe that highly active antiretroviral therapy (HAART) is effective (p<0.01). Among those who accessed care, 33% subsequently discontinued care, most because they did not qualify for HAART. Factors cited as barriers to access included stigma, denial, poor services, and lack of money. Factors that were cited as making care attractive included health education, counseling, free services, and compassion.
A substantial number of women exiting maternal care do not transit to HIV care programs. Partner involvement, a standardized referral process and more comprehensive HIV education for mothers diagnosed with HIV during pregnancy may facilitate successful transitions between PMTCT and HIV care programs.
PMTCT; access; HIV
To determine the prevalence and correlates of neonatal conjunctivitis in infants born to human immunodeficiency virus type 1 (HIV-1) infected mothers.
This was a nested case-control study within a perinatal HIV-1 cohort. HIV-1 seropositive mothers were enrolled during pregnancy and mother-infant pairs followed after delivery with assessment for neonatal conjunctivitis at 48 hours and up to 4 weeks after birth. Genital infections (chlamydia, gonorrhea, syphilis, trichomonas, bacterial vaginosis, and candida) were screened for at 32 weeks gestation. Mothers received treatment for genital infections diagnosed during pregnancy and short-course zidovudine. Newborns did not receive ocular prophylaxis at hospital deliveries. Multivariate logistic regression models were used to determine cofactors for neonatal conjunctivitis overall and stratified for infant HIV-1 status.
Four hundred and fifty-two infants were assessed and 101 (22.3%) had neonatal conjunctivitis during the first month postpartum. In multivariate analyses using odds ratios (OR) and confidence intervals (CI), neonatal conjunctivitis was associated with neonatal sepsis (adjusted OR 21.95, 95% CI 1.76, 274.61), birth before arrival to hospital (adjusted OR 13.91, 95% CI 1.39, 138.78) and birth weight (median 3.4 versus 3.3 kilograms, p=0.016, OR 1.79, 95% CI 1.01, 3.15). Infant HIV-1 infection was not associated with conjunctivitis.
Despite detection and treatment of genital infections during pregnancy, neonatal conjunctivitis was frequently diagnosed in infants born to HIV-1 infected mothers suggesting a need for increased vigilance and prophylaxis for conjunctivitis in these infants. Neonatal sepsis, birth before arrival to hospital, and higher birthweight are factors that may predict higher risk of neonatal conjunctivitis in this population.
Case-control; HIV; Maternal; Neonatal conjunctivitis; Risk factors
Co-infection with herpes simplex virus type 2 (HSV-2) has been associated with increased HIV-1 RNA levels and immune activation, two predictors of HIV-1 progression. The impact of HSV-2 on clinical outcomes among HIV-1 infected pregnant women is unclear.
HIV-1 infected pregnant women in Nairobi were enrolled antenatally and HSV-2 serology was obtained. HIV-1 RNA and CD4 count were serially measured for 12–24 months postpartum. Survival analysis using endpoints of death, opportunistic infection (OI), and CD4<200 cells µL, and linear mixed models estimating rate of change of HIV-1 RNA and CD4, were used to determine associations between HSV-2 serostatus and HIV-1 progression.
Among 296 women, 254 (86%) were HSV-2-seropositive. Only 30 (10%) women had prior or current genital ulcer disease (GUD); median baseline CD4 count was 422 cells µL. Adjusting for baseline CD4, women with GUD were significantly more likely to have incident OIs (adjusted hazard ratio (aHR) 2.79, 95% CI: 1.33–5.85), and there was a trend for association between HSV-2-seropositivity and incident OIs (aHR 3.83, 95% CI: 0.93–15.83). Rate of change in CD4 count and HIV-1 RNA did not differ by HSV-2 status or GUD, despite a trend toward higher baseline HIV-1 RNA in HSV-2-seropositive women (4.73 log10 copies/ml vs. 4.47 log10 copies/ml, P = 0.07).
HSV-2 was highly prevalent and pregnant HIV-1 infected women with GUD were significantly more likely to have incident OIs than women without GUD, suggesting that clinically evident HSV-2 is a more important predictor of HIV-1 disease progression than asymptomatic HSV-2.
Breast-feeding by infants exposed to human immunodeficiency virus type 1 (HIV-1) provides an opportunity to assess the role played by repeated HIV-1 exposure in eliciting HIV-1–specific immunity and in defining whether immune responses correlate with protection from infection.
Breast-feeding infants born to HIV-1–seropositive women were assessed for HLA-selected HIV-1 peptide–specific cytotoxic T lymphocyte interferon (IFN)–γ responses by means of enzyme-linked immunospot (ELISpot) assays at 1, 3, 6, 9, and 12 months of age. Responses were deemed to be positive when they reached ⩾50 HIV-1–specific sfu/1 × 106 peripheral blood mononuclear cells (PBMCs) and were at least twice those of negative controls.
A total of 807 ELISpot assays were performed for 217 infants who remained uninfected with HIV-1 at ∼12 months of age; 101 infants (47%) had at least 1 positive ELISpot result (median, 78–170 sfu/1 × 106 PBMCs). The prevalence and magnitude of responses increased with age (P = .01 and P = .007, respectively); the median log10 value for HIV-1–specific IFN-γ responses increased by 1.0 sfu/1 × 106 PBMCs/month (P < .001) between 1 and 12 months of age. Of 141 HIV-1–uninfected infants with 1-month ELISpot results, 10 (7%) acquired HIV-1 infection (0/16 with positive vs. 10/125 [8%] with negative ELISpot results; P = .6). Higher values for log10 HIV-1–specific spot-forming units at 1 month of age were associated with a decreased risk of HIV-1 infection, adjusted for maternal HIV-1 RNA level (adjusted hazard ratio, 0.09 [95% confidence interval, 0.01–0.72]).
Breast-feeding HIV-1–exposed uninfected infants frequently had HIV-1–specific IFN-γ responses. Greater early HIV-1–specific IFN-γ responses were associated with decreased HIV-1 acquisition.
There is limited information regarding the pattern and correlates of viral replication in vertically HIV-1–infected children and its role on their outcomes in resource-limited settings.
HIV-1–infected infants were followed from birth to 24 months. Serial HIV-1 RNA levels were compared in infants infected in utero (<48 hours), peripartum (48 hours–1 month), and late postnatal (after 1 month). Cofactors for viral peak [highest viral load (VL) within 6 months of infection] and set point and mortality were determined.
Among 85 HIV-1–infected infants, 24 were infected in utero, 41 peripartum, 13 late postnatal; 7 had no 48-hour assay. HIV-1 VL set point was significantly lower in infants infected >1 month vs. ≤1 month (5.59 vs. 6.24 log10 copies per milliliter, P = 0.01). Maternal VL correlated with peak infant VL (P < 0.001). Univariately, infant peak and set point VL and 6-month CD4% <15% predicted mortality; and 6-month CD4% <15% remained independently predictive in multivariate analyses (hazard ratio = 4.85, 95% confidence interval: 1.90 to 12.36).
Infants infected after the age of 1 month contained virus better than infants infected before 1 month of age. Maternal VL predicted infant VL, which, in turn was associated with early mortality.
HIV-1; mortality; pathogenesis; pediatric; timing of HIV-1 infection; viral load
There are limited data regarding the relative merits of biomarkers as predictors of mortality or time to initiation of antiretroviral therapy (ART).
We evaluated the usefulness of the CD4 cell count, CD4 cell percentage (CD4%), human immunodeficiency virus type 1 (HIV-1) load, total lymphocyte count (TLC), body mass index (BMI), and hemoglobin measured at 32 weeks’ gestation as predictors of mortality in a cohort of HIV-1–infected women in Nairobi, Kenya. Sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic (ROC) curve (AUC) were determined for each biomarker separately, as well as for the CD4 cell count and the HIV-1 load combined.
Among 489 women with 10,150 person-months of follow-up, mortality rates at 1 and 2 years postpartum were 2.1% (95% confidence interval [CI], 0.7%–3.4%) and 5.5% (95% CI, 3.0%–8.0%), respectively. CD4 cell count and CD4% had the highest AUC value (>0.9). BMI, TLC, and hemoglobin were each associated with but poorly predictive of mortality (PPV, <7%). The HIV-1 load did not predict mortality beyond the CD4 cell count.
The CD4 cell count and CD4% measured during pregnancy were both useful predictors of mortality among pregnant women. TLC, BMI, and hemoglobin had a limited predictive value, and the HIV-1 load did not predict mortality any better than did the CD4 cell count alone.
Deworming HIV-1 infected individuals may delay HIV-1 disease progression. It is important to determine the prevalence and correlates of HIV-1/helminth co-infection in helminth-endemic areas.
HIV-1 infected individuals (CD4>250 cells/ul) were screened for helminth infection at ten sites in Kenya. Prevalence and correlates of helminth infection were determined. A subset of individuals with soil-transmitted helminth infection was re-evaluated 12 weeks following albendazole therapy.
Of 1,541 HIV-1 seropositive individuals screened, 298 (19.3%) had detectable helminth infections. Among individuals with helminth infection, hookworm species were the most prevalent (56.3%), followed by Ascaris lumbricoides (17.1%), Trichuris trichiura (8.7%), Schistosoma mansoni (7.1%), and Stongyloides stercoralis (1.3%). Infection with multiple species occurred in 9.4% of infections. After CD4 count was controlled for, rural residence (RR 1.40, 95% CI: 1.08–1.81), having no education (RR 1.57, 95% CI: 1.07–2.30), and higher CD4 count (RR 1.36, 95% CI: 1.07–1.73) remained independently associated with risk of helminth infection. Twelve weeks following treatment with albendazole, 32% of helminth-infected individuals had detectable helminths on examination. Residence, education, and CD4 count were not associated with persistent helminth infection.
Among HIV-1 seropositive adults with CD4 counts above 250 cells/mm3 in Kenya, traditional risk factors for helminth infection, including rural residence and lack of education, were associated with co-infection, while lower CD4 counts were not.
Over one-third of people worldwide are currently infected with parasitic worms. The majority of these infections occur in sub-Saharan Africa, where over half of the population may be infected with at least one type of parasitic worm. HIV infection is also common in many of these countries, and there is significant geographic overlap in the presence of HIV and worm infection. Several studies have suggested that treatment of worm infections in people with HIV may delay the progression of HIV disease. Treatment has been shown to both decrease levels of the HIV virus in the blood of people with HIV and to increase the number of immune cells (CD4 cells) targeted by HIV. It is important to determine which populations of HIV-infected individuals are at greatest risk of worm infection in order to develop potential interventions for the treatment and prevention of worm infection in HIV-infected individuals. We report findings from a large study examining the prevalence and associated co-factors for worm infection among individuals at ten sites in Kenya.
Cytomegalovirus (CMV) is an important pathogen in healthy neonates and individuals with human immunodeficiency virus (HIV-1). The objective of this study was to determine whether the detection of CMV DNA (CMV DNAemia) in maternal plasma was associated with mortality in HIV-1 infected women or their infants.
A longitudinal study was designed to examine the relationship between maternal CMV DNAemia and maternal-infant mortality during two years postpartum. Sixty-four HIV-1 infected women and their infants were studied. CMV DNA loads were quantified in plasma from the mothers near the time of delivery. Baseline maternal CD4 counts, CD4%, HIV-1 RNA, and CMV DNAemia were evaluated as covariates of subsequent maternal or infant mortality in univariate and multivariate Cox regression.
CMV DNA was detected in 11/64 (17%) of the HIV-1 infected women. HIV-1 and CMV viral load were strongly correlated in CMV DNAemic women (ρ=0.84, p=0.001). Detection of CMV DNAemia was associated with decreased maternal survival at 24 months postpartum (log-rank p=0.006). Additionally, HIV-1 infected infants born to CMV DNAemic women had a 4-fold increased risk of mortality during 24 months of follow-up. Maternal CMV DNAemia remained a significant risk factor for mortality in HIV-1 infected infants after adjusting for maternal CD4 cells/mm3 (adjusted HR=4.3, CI=1.4–13), CD4% (HR=3.2, CI=1.0–10), HIV-1 viral load (HR=4.1, CI=1.4–12) or maternal death (HR=3.7, CI=1.0–13).
Maternal plasma CMV DNAemia identified a subgroup of Kenyan women and infants at high risk for death in the two years following delivery.
cytomegalovirus; vertical transmission; viral load; infant mortality
Several co-infections have been shown to impact the progression of HIV-1 infection. We sought to determine if treatment of helminth co-infection in HIV-1 infected adults impacted markers of HIV-1 disease progression.
To date there have been no randomized trials to examine the effects of soil-transmitted helminth eradication on markers of HIV-1 progression.
A randomized, double-blind, placebo-controlled trial of albendazole (400mg daily for three days) in antiretroviral-naïve HIV-1 infected adults (CD4 >200 cells/mm3) with soil-transmitted helminth infection was conducted at ten sites in Kenya (Clinical Trials.gov NCT00130910). CD4 and plasma HIV-1 RNA levels at 12 weeks following randomization were compared in the trial arms using linear regression, adjusting for baseline values.
Of 1,551 HIV-1 infected individuals screened for helminth-infection, 299 were helminth-infected. 234 adults were enrolled and underwent randomization and 208 individuals were included in intent-to-treat analyses. Mean CD4 count was 557 cells/mm3 and mean plasma viral load was 4.75 log10 copies/mL at enrolment. Albendazole therapy resulted in significantly higher CD4 counts among individuals with Ascaris lumbricoides infection after 12 weeks of follow up (+109 cells/mm3; 95% CI +38.9 to +179.0, p=0.003) and a trend for 0.54 log10 lower HIV-1 RNA levels (p=0.09). These effects were not seen with treatment of other species of soil-transmitted helminths.
Treatment of A. lumbricoides with albendazole in HIV-1 co-infected adults resulted in significantly increased CD4 counts during 3-month follow-up. Given the high prevalence of A. lumbricoides infection worldwide, deworming may be an important potential strategy to delay HIV-1 progression.
HIV-1 progression; helminth; co-infection
During the past decade, donor funding for health interventions in Kenya and other African countries has risen sharply. Focused on high-profile diseases such as HIV/AIDS, these funds create islands of intervention in a sea of under-resourced public health services. This paper draws on ethnographic research conducted in HIV clinics and in a public hospital to examine how health workers experience and reflect upon the juxtaposition of ‘global’ medicine with ‘local’ medicine. We show that health workers face an uneven playing field. High-prestige jobs are available in HIV research and treatment, funded by donors, while other diseases and health issues receive less attention. Outside HIV clinics, patient's access to medicines and laboratory tests is expensive, and diagnostic equipment is unreliable. Clinicians must tailor their decisions about treatment to the available medical technologies, medicines and resources. How do health workers reflect on working in these environments and how do their experiences influence professional ambitions and commitments?
national health systems; vertical disease programmes; hospital care; Kenya/East Africa; ethnography; health workers