Search tips
Search criteria

Results 1-25 (143)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
more »
1.  Compartmentalized Cytomegalovirus Replication and Transmission in the Setting of Maternal HIV-1 Infection 
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.
PMCID: PMC3905754  PMID: 24192386
cytomegalovirus; human immunodeficiency virus; neonates; opportunistic infection; compartmentalization
2.  Contribution of HIV infection to mortality among cancer patients in Uganda 
AIDS (London, England)  2013;27(18):2933-2942.
HIV infection is associated with cancer risk. This relationship has resulted in a growing cancer burden, especially in resource-limited countries where HIV is highly prevalent. Little is known, however, about how HIV affects cancer survival in these settings. We therefore investigated the role of HIV in cancer survival in Uganda.
Retrospective cohort (N = 802).
Eligible cancer patients were residents of Kyadondo County, at least 18 years of age at cancer diagnosis, and diagnosed between 2003 and 2010 with one of the following: breast cancer, cervical cancer, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, or esophageal cancer. Patients were classified as HIV-infected at cancer diagnosis based on a documented positive HIV antibody test, medical history indicating HIV infection, or an HIV clinic referral letter. The primary outcome, vital status at 1 year following cancer diagnosis, was abstracted from the medical record or determined through linkage to the national hospice database. The risk of death during the year after cancer diagnosis was compared between cancer patients with and without evidence of HIV infection using Cox proportional hazards regression.
HIV-infected cancer patients in Uganda experienced a more than two-fold increased risk of death during the year following cancer diagnosis compared to HIV-uninfected cancer patients [hazard ratio 2.28; 95% confidence interval (CI) 1.61–3.23]. This association between HIV and 1-year cancer survival was observed for both cancers with (hazard ratio 1.56; 95% CI 1.04–2.34) and without (hazard ratio 2.68; 95% CI 1.20–5.99) an infectious cause.
This study demonstrates the role of HIV in cancer survival for both cancers with and without an infectious cause in a resource-limited, HIV-endemic setting.
PMCID: PMC4319357  PMID: 23921614
cancer in Africa; cancer survival; HIV; immunosuppression; Uganda
3.  Bacterial vaginosis and the risk of Trichomonas vaginalis acquisition among HIV-1 negative women 
Sexually transmitted diseases  2014;41(2):123-128.
The vaginal microbiota may play a role in mediating susceptibility to sexually transmitted infections, including Trichomonas vaginalis (TV).
Data were analyzed from HIV-1 seronegative women participating in HIV Prevention Trials Network Protocol 035. At quarterly visits for up to 30 months, participants completed structured interviews and specimens were collected for genital tract infection testing. TV was detected by saline microscopy. BV was characterized by Gram stain using the Nugent score (BV=7-10; intermediate=4-6; normal=0-3 [reference group]). Cox proportional hazards models stratified by study site were used to assess the association between Nugent score category at the prior quarterly visit and TV acquisition.
In this secondary analysis, 2,920 participants from Malawi, South Africa, USA, Zambia and Zimbabwe contributed 16,259 follow-up visits. BV was detected at 5,680 (35%) visits and TV was detected at 400 (2.5%) visits. Adjusting for age, marital status, hormonal contraceptive use, unprotected sex in the last week and TV at baseline, intermediate Nugent score and BV at the prior visit were associated with an increased risk of TV (intermediate score: adjusted hazard ratio [aHR]=1.73, 95% confidence interval [CI] 1.21-2.19; BV: aHR=2.40, 95% CI 1.92-3.00). Sensitivity analyses excluding 211 participants with TV at baseline were similar to those from the full study population (intermediate score: aHR=1.54, 95% CI 1.10-2.14; BV: aHR=2.23, 95% CI 1.75-2.84)
Women with a Nugent score >3 were at an increased risk of acquiring TV. If this relationship is causal, interventions that improve the vaginal microbiota could contribute to reductions in TV incidence.
PMCID: PMC4128240  PMID: 24413493
Bacterial vaginosis; Trichomonas vaginalis; vaginal microbiota; sexually transmitted disease acquisition; prospective cohort
4.  Use of Principal Components Analysis and Protein Microarray to Explore the Association of HIV-1-Specific IgG Responses with Disease Progression 
The role of HIV-1-specific antibody responses in HIV disease progression is complex and would benefit from analysis techniques that examine clusterings of responses. Protein microarray platforms facilitate the simultaneous evaluation of numerous protein-specific antibody responses, though excessive data are cumbersome in analyses. Principal components analysis (PCA) reduces data dimensionality by generating fewer composite variables that maximally account for variance in a dataset. To identify clusters of antibody responses involved in disease control, we investigated the association of HIV-1-specific antibody responses by protein microarray, and assessed their association with disease progression using PCA in a nested cohort design. Associations observed among collections of antibody responses paralleled protein-specific responses. At baseline, greater antibody responses to the transmembrane glycoprotein (TM) and reverse transcriptase (RT) were associated with higher viral loads, while responses to the surface glycoprotein (SU), capsid (CA), matrix (MA), and integrase (IN) proteins were associated with lower viral loads. Over 12 months greater antibody responses were associated with smaller decreases in CD4 count (CA, MA, IN), and reduced likelihood of disease progression (CA, IN). PCA and protein microarray analyses highlighted a collection of HIV-specific antibody responses that together were associated with reduced disease progression, and may not have been identified by examining individual antibody responses. This technique may be useful to explore multifaceted host–disease interactions, such as HIV coinfections.
PMCID: PMC3931433  PMID: 24134221
5.  HPTN 035 Phase II/IIb Randomized Safety and Effectiveness Study of the Vaginal Microbicides BufferGel and 0.5% PRO 2000 for the Prevention of Sexually Transmitted Infections in Women 
Sexually transmitted infections  2014;90(5):363-369.
To estimate the effectiveness of candidate microbicides BufferGel and 0.5% PRO 2000 Gel (P) (PRO 2000) for prevention of non-ulcerative sexually transmitted infections (STIs).
Between 2005 and 2007, 3099 women were enrolled in HIV Prevention Trials Network (HPTN) protocol 035, a phase II/IIb evaluation of the safety and effectiveness of BufferGel and PRO 2000 for prevention of sexually transmitted infections, including Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), and Trichomonas vaginalis (TV). Incidences of STIs were determined by study arm, and hazard ratios (HRs) of BufferGel and PRO 2000 versus placebo gel or no gel control groups were computed using discrete time Andersen-Gill proportional hazards model.
The overall incidence rates were 1.6/100 person-years at risk (PYAR) for GC, 3.9/100 PYAR for CT, and 15.3/100 PYAR for TV. For BufferGel versus placebo gel, HRs were 0.99 (95% CI 0.49–2.00), 1.00 (95% CI 0.64–1.57), and 0.95 (95% CI 0.71–1.25) for prevention of GC, CT, and TV respectively. For PRO 2000, HRs were 1.66 (95% CI 0.90–3.06), 1.16 (95% CI 0.76–1.79), and 1.18 (95% CI 0.90–1.53) for prevention of GC, CT, and TV respectively.
The incidence of STIs was high during HPTN 035 despite provision of free condoms and comprehensive risk-reduction counselling, highlighting the need for effective STI prevention programmes in this population. Unfortunately, candidate microbicides BufferGel and PRO2000 had no protective effect against gonorrhoea, Chlamydia, or trichomoniasis.
PMCID: PMC4278566  PMID: 24898857
Neisseria gonorrhoeae; Chlamydia trachomatis; Trichomonas; microbicides; prevention
6.  Association between Cellular Immune Activation, Target Cell Frequency, and Risk of Human Immunodeficiency Virus Type 1 Superinfection 
Journal of Virology  2014;88(10):5894-5899.
We performed a case-control study of women at risk of HIV-1 superinfection to understand the relationship between immune activation and HIV-1 acquisition. An increase in the frequency of HIV-1 target cells, but not in other markers of T cell activation, was associated with a 1.7-fold increase in the odds of superinfection. This suggests that HIV-1 acquisition risk is influenced more by the frequency of target cells than by the generalized level of immune activation.
PMCID: PMC4019101  PMID: 24623424
7.  Evidence for Efficient Vertical Transfer of Maternal HIV-1 Envelope-Specific Neutralizing Antibodies but No Association of Such Antibodies with Reduced Infant Infection 
Little is known about the efficiency of vertical transfer of HIV-1-specific antibodies. We compared antibody levels in plasma from 60 mother-infant pairs near the time of birth, including 14 breastfeeding transmission pairs. The Envelope binding titers were strongly correlated (r=0.91, p<0.0001) and similar (1.4-fold greater in maternal plasma) between a mother and her corresponding infant as were the neutralizing antibody (Nab) levels (r = 0.80, p<0.0001; 1.3-fold higher), suggesting efficient transfer. There was no significant difference in Nab responses between transmitting and non-transmitting mothers, although there was a trend for transmitting mothers to have higher HIV-1-specific Nabs.
PMCID: PMC3805370  PMID: 23774880
Mother-to-child transfer; HIV-1 envelope; Neutralizing antibodies
8.  Toll-like Receptor (TLR) variants are associated with infant HIV-1 acquisition and peak plasma HIV-1 RNA level 
AIDS (London, England)  2013;27(15):2431-2439.
We evaluated the association of single nucleotide polymorphisms (SNPs) in TLRs with infant HIV-1 acquisition and viral control.
Infant HIV-1 outcomes were assessed in a Kenyan perinatal HIV-1 cohort.
Infants were genotyped for six candidate and 118 haplotype-tagging polymorphisms in TLRs 2, 3, 4, 7, 8, and 9, MYD88 and TIRAP. Cox proportional hazards and linear regression were performed to assess associations with time to HIV-1 acquisition, time to infant mortality, and peak viral load (VL).
Among 368 infants, 56 (15%) acquired HIV-1 by month 1 and 17 (4.6%) between 1 and 12 months. Infants with the TLR9 1635A (rs352140) variant were more likely to acquire HIV-1 by 1 month (HR=1.81, 95% confidence interval [CI] =1.05-3.14, p=0.033) and by 12 months (HR=1.62, CI=1.01-2.60, p=0.044) in dominant models adjusted for maternal plasma HIV-1 RNA level and genetic ancestry. Among 56 infants infected at ≤1 month of age, ≥1 copy of the TLR9 1635A allele was associated with a 0.58 log10 c/ml lower peak VL (p=0.002). Female infants with ≥1 copy of the TLR8 1G (rs3764880) variant had a 0.78 log10 c/ml higher peak VL (p=0.0009) and having ≥1 copy of the C allele for a haplotype tagging TLR7 variant (rs1634319) was associated with a 0.80 log10 c/ml higher peak VL in female infants (p=0.0003).
In this African perinatal cohort, we found several TLR polymorphisms associated with HIV-1 acquisition and progression. Defining mechanisms for these TLR associations may inform HIV-1 prevention strategies that leverage innate responses.
PMCID: PMC4124859  PMID: 24037211
pediatric HIV; mother-to-child transmission; genetic epidemiology; HIV genetics; innate immunity; single nucleotide polymorphisms; toll-like receptors; TLRs
9.  Prevalence, Perceptions and Correlates of Pediatric HIV Disclosure in an HIV Treatment Program in Kenya 
AIDS care  2012;25(9):1067-1076.
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.
PMCID: PMC3626761  PMID: 23256520
disclosure; pediatric; HIV; stigma; adherence
10.  Comparing Papanicolau smear, visual inspection with acetic acid and human papillomavirus cervical cancer screening methods among HIV-positive women by immune status and antiretroviral therapy 
AIDS (London, England)  2013;27(18):2909-2919.
A rigorous comparison of cervical cancer screening methods utilizing data on immune status, antiretroviral therapy (ART) and colposcopy-directed biopsy has not been performed among HIV-positive women.
Between June and November 2009, 500 HIV-positive women were enrolled at an HIV treatment clinic in Nairobi, Kenya, and underwent Papanicolau (Pap) smear, visual inspection with acetic acid (VIA), human papillomavirus (HPV) and colposcopy-directed biopsy (gold standard). Positive Pap smear (ASCUS+, LSIL+, HSIL+), VIA, HPV and their combinations were compared with CIN2/3+. Sensitivity, specificity and AUC (sensitivity and 1–specificity) were compared using pairwise tests and multivariate logistic regression models that included age, CD4+ cell count and ART duration.
Of 500 enrolled, 498 samples were collected. On histology, there were 172 (35%) normal, 186 (37%) CIN1, 66 (13%) CIN2, 47 (9%) CIN3 and 27 (5%) indeterminate. Pap (ASCUS+) was the most sensitive screening method (92.7%), combination of both Pap (HSIL+) and VIA positive was the most specific (99.1%) and Pap (HSIL+) had the highest AUC (0.85). In multivariate analyses, CD4+ cell count of 350 cells/μl or less was associated with decreased HPV specificity (P = 0.002); ART duration of less than 2 years was associated with decreased HPV (P = 0.01) and VIA (P = 0.03) specificity; and age less than 40 years was associated with increased VIA sensitivity (P < 0.001) and decreased HPV specificity (P = 0.005).
Pap smear is a robust test among HIV-positive women regardless of immune status or ART duration. Results should be cautiously interpreted when using HPV among those younger, immunosuppressed or on ART less than 2 years, and when using VIA among those aged 40 years or more.
PMCID: PMC4007364  PMID: 23842133
cervical cancer screening; HIV-1; human papillomavirus; Papanicolau smear; visual inspection with acetic acid
11.  Improving Vaginal Health in Women at Risk for HIV-1: Results of a Randomized Trial 
The Journal of infectious diseases  2008;197(10):1361-1368.
Vaginal infections are common and have been associated with increased HIV-1 risk.
We conducted a randomized trial of monthly oral directly observed treatment for reducing vaginal infections in Kenyan women at risk for HIV-1. Trial interventions included metronidazole 2 grams plus fluconazole 150 milligrams versus identical metronidazole and fluconazole placebos. The primary endpoints were bacterial vaginosis (BV), vaginal candidiasis, trichomoniasis, and colonization with Lactobacillus (, NCT00170430).
Of 310 HIV-1-seronegative female sex workers enrolled (155 per arm), 303 were included in the primary endpoints analysis. Median follow-up was 12 visits in both study arms (p=0.8). Compared to controls, women receiving the intervention had fewer episodes of BV (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.49-0.63), and more frequent vaginal colonization with Lactobacillus species (HR 1.47, 95% CI 1.19-1.80) and hydrogen peroxide-producing Lactobacillus species (HR 1.63, 95% CI 1.16-2.27). Vaginal candidiasis (HR 0.84, 95% CI 0.67-1.04) and trichomoniasis (HR 0.55, 95% CI 0.27-1.12) were reduced in treated women compared to controls, although not significantly.
Periodic presumptive treatment reduced BV and promoted normal vaginal flora. Vaginal health interventions have the potential to provide simple, female-controlled approaches for reducing HIV-1 risk.
PMCID: PMC4122228  PMID: 18444793
Bacterial vaginosis; vaginal candidiasis; Trichomonas vaginalis; Lactobacillus; HIV-1; randomized trial; women; Africa
12.  Mode of delivery and postpartum HIV-1 disease progression and mortality in a Kenyan cohort 
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.
PMCID: PMC4133616  PMID: 25086834
HIV; Mode of delivery; Cesarean section; HIV-1 disease progression; Maternal mortality
13.  Performance of the Integrated Management of Childhood Illness (IMCI) Algorithm for Diagnosis of HIV-1 Infection among Kenyan Infants 
AIDS (London, England)  2012;26(15):1935-1941.
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.
PMCID: PMC4113472  PMID: 22824627
IMCI; HIV; infant; Africa; clinical algorithm; pediatric
14.  HIV-1 Specific IgA Detected in Vaginal Secretions of HIV Uninfected Women Participating in a Microbicide Trial in Southern Africa Are Primarily Directed Toward gp120 and gp140 Specificities 
PLoS ONE  2014;9(7):e101863.
Many participants in microbicide trials remain uninfected despite ongoing exposure to HIV-1. Determining the emergence and nature of mucosal HIV-specific immune responses in such women is important, since these responses may contribute to protection and could provide insight for the rational design of HIV-1 vaccines.
Methods and Findings
We first conducted a pilot study to compare three sampling devices (Dacron swabs, flocked nylon swabs and Merocel sponges) for detection of HIV-1-specific IgG and IgA antibodies in vaginal secretions. IgG antibodies from HIV-1-positive women reacted broadly across the full panel of eight HIV-1 envelope (Env) antigens tested, whereas IgA antibodies only reacted to the gp41 subunit. No Env-reactive antibodies were detected in the HIV-negative women. The three sampling devices yielded equal HIV-1-specific antibody titers, as well as total IgG and IgA concentrations. We then tested vaginal Dacron swabs archived from 57 HIV seronegative women who participated in a microbicide efficacy trial in Southern Africa (HPTN 035). We detected vaginal IgA antibodies directed at HIV-1 Env gp120/gp140 in six of these women, and at gp41 in another three women, but did not detect Env-specific IgG antibodies in any women.
Vaginal secretions of HIV-1 infected women contained IgG reactivity to a broad range of Env antigens and IgA reactivity to gp41. In contrast, Env-binding antibodies in the vaginal secretions of HIV-1 uninfected women participating in the microbicide trial were restricted to the IgA subtype and were mostly directed at HIV-1 gp120/gp140.
PMCID: PMC4108330  PMID: 25054205
15.  Lipid Changes in Kenyan HIV-1-Infected Infants Initiating Highly Active Antiretroviral Therapy by One Year of Age 
Early highly active antiretroviral therapy (HAART) is recommended for HIV-1 infected infants. There are limited data on lipid changes during infant HAART.
Non-fasting total (TC), low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol, and triglycerides (TG) were measured at 0, 6 and 12 months. Correlates of lipid levels and changes post-HAART were assessed using linear regression.
Among 115 infants, pre-HAART median age was 3.8 months, CD4% was 19%, and weight-for-age z-score (WAZ) was −2.42. Pre-HAART median lipid levels were: TC, 108.7 mg/dl, LDL, 42.5 mg/dl, HDL, 29.4 mg/dl and TG, 186.9 mg/dl. Few infants had abnormally high TC (6.2%) or LDL (5.6%), but many had low HDL (76.5%) or high TG (69.6%). Higher pre-HAART WAZ and HAZ were each associated with higher pre-HAART TC (P=0.04 and P=0.01) and LDL (P=0.02 and P=0.008). From 0–6 months post-HAART, TC (P<0.0001), LDL (P<0.0001), and HDL (P<0.0001) increased significantly, and 23.1% (P=0.002), 14.0% (P=0.2), 31.3% (P<0.0001), and 50.8% (P=0.2) of infants had abnormally high TC, high LDL, low HDL, and high TG, respectively. Changes in TC and HDL were each associated with higher gain in WAZ (P=0.03 and P=0.01) and HAZ (P=0.01 and P=0.007). Increased change in LDL was associated with higher gain in HAZ (P=0.03). Infants on protease inhibitor (PI)-HAART had smaller HDL increase (P=0.004).
Infants had substantive increases in lipids, which correlated with growth. Increases in HDL were attenuated by PI-HAART. It is important to determine clinical implications of these changes.
PMCID: PMC3737429  PMID: 23385950
lipids; pediatric HIV-1; highly active antiretroviral therapy; infants; Africa
16.  Clinical and Virologic Manifestations of Primary Epstein-Barr Virus (EBV) Infection in Kenyan Infants Born to HIV-Infected Women 
The Journal of Infectious Diseases  2013;207(12):1798-1806.
Background. Human immunodeficiency virus (HIV) infection is a risk factor for Epstein-Barr virus (EBV)–associated lymphomas. Characterizing primary infection may elucidate risk factors for malignancy.
Methods. To describe clinical and virologic manifestations of primary EBV infection among infants born to HIV-infected women, specimens were utilized from a cohort study conducted in Nairobi, Kenya. HIV and EBV viral loads were measured serially in plasma. EBV serology was performed on EBV DNA–negative infants. Monthly clinical examinations were performed by pediatricians.
Results. The probability of EBV infection by 1 year of age was .78 (95% CI, .67–.88) in HIV-infected and .49 (95% CI, .35–.65) in HIV-uninfected infants (P < .0001). At 2 years, probability of EBV infection was .96 (95% CI, .89–.99) in HIV-infected infants. Peak EBV loads were higher in HIV-infected versus HIV-uninfected infants (median 2.6 vs 2.1 log10 copies/mL; P < .0001). The majority of HIV-infected infants had detectable EBV DNA for >3 months (79%). Primary EBV infection was associated with cough, fever, otitis media, pneumonia, hepatomegaly, splenomegaly, and hospitalization in HIV-infected infants; conjunctivitis and rhinorrhea in HIV-uninfected infants.
Conclusions. EBV infection occurs early in infants born to HIV-infected women. HIV infection was associated with more frequent and higher quantity EBV DNA detection.
PMCID: PMC3654744  PMID: 23493724
EBV; primary infection; HIV; pediatric; herpesviruses
17.  A prospective cohort study comparing the effect of single-dose 2g metronidazole on Trichomonas vaginalis infection in HIV-seropositive versus HIV-seronegative women 
Sexually transmitted diseases  2013;40(6):499-505.
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.
PMCID: PMC3676301  PMID: 23677023
Trichomonas vaginalis; metronidazole; efficacy; persistence; HIV infection; nevirapine; antiretroviral therapy
18.  Antibody-dependent cell-mediated virus inhibition (ADCVI) antibody activity does not correlate with risk of HIV-1 superinfection 
Previous studies of HIV-infected women with high risk behavior have indicated that neither neutralizing antibody nor cellular immunity elicited by an initial HIV-1 infection is associated with protection against superinfection with a different HIV-1 strain. Here, we measured antibody-dependent cell-mediated virus inhibition (ADCVI) antibody activity in the plasma of 12 superinfected cases and 36 singly infected matched controls against 2 heterologous viruses. We found no association between plasma ADCVI activity and superinfection status. ADCVI antibody activity against heterologous virus elicited by the original infection may not contribute to preventing a superinfecting HIV-1.
PMCID: PMC3625514  PMID: 23344546
antibody-dependent cell-mediated virus inhibition; ADCVI; HIV-1; superinfection; primary infection; clade A
19.  Appropriateness of hydroxyethylcellulose gel as a placebo control in vaginal microbicide trials: A comparison of the two control arms of HPTN 035 
To compare the two control arms of HPTN 035 (a hydroxyethylcellulose (HEC) gel control arm and a no gel control arm) to assess behavioral effects associated with gel use and direct causal effects of the HEC gel on STIs, pregnancy, and genital safety.
Randomized trial with one blinded (HEC gel) and one open label (no gel) control arms.
HIV-uninfected, sexually active women were randomized into the HEC gel arm (n=771) and into the no gel arm (n=772) in five countries. Participants in the HEC gel arm were instructed to insert the study gel intravaginally <1 hour before each vaginal sex act. Data on sexual behavior, adherence, safety, pregnancy, and STIs were collected quarterly for 12 to 30 months of follow-up.
During follow-up, mean reported condom use in the past week was significantly higher in the no gel arm (81% versus 70%, p<0.001). There were no significant differences, after adjusting for this differential condom use, between the two arms in rates of genital safety events, pregnancy outcomes, or STIs, including HIV-1.
In this large randomized trial, we found no significant differences between the no gel and HEC gel arms in rates of genital safety events, pregnancy outcomes, or STIs. These results aid interpretation of the results of previous vaginal microbicide trials that used the HEC gel as a control. The HEC gel is suitable as a control for ongoing and future vaginal microbicide studies.
PMCID: PMC3625489  PMID: 23334506
HIV prevention; vaginal microbicide; placebo; women; sexually transmitted infections
20.  Incidence and Correlates of Chlamydia trachomatis Infection in a High Risk Cohort of Kenyan Women 
Sexually transmitted diseases  2013;40(3):10.1097/OLQ.0b013e318272fe45.
In Africa, data on Chlamydia trachomatis infection are scarce because reliable diagnosis is costly and not widely available. Our objective was to evaluate the incidence and correlates of C. trachomatis infection among high-risk Kenyan women.
We conducted prospective cohort analyses using data from a cohort of women who reported transactional sex. C. trachomatis testing was performed using the Gen-Probe Aptima GC/CT Detection System. We used Andersen-Gill proportional hazards modeling to evaluate correlates of C. trachomatis.
Between August 2006 and December 2010, 865 women contributed 2011 person-years of observation. Sixty-four women experienced 101 episodes of C. trachomatis infection (incidence rate of 5.0/100 person-years). There was a large difference in incidence by age group: those below 25 years had an incidence of 27.6 per 100 person-years (95% CI 16.3 – 46.5), those 25 to 34 years old had an incidence of 8.4 per 100 person-years (95% CI 6.4 – 11.0), and those 35 years old and above had an incidence of 2.6 per 100 person-years (95% CI 1.8 – 3.6). In multivariate analyses, younger age (<25 years and 25–34 years versus ≥35 years; hazard ratio [HR] 8.49 95% CI 4.1–17.7 and HR 2.9 95% CI 1.7–5.0 respectively), depot medroxyprogesterone acetate use (HR 1.8 95% CI 1.1–3.0) and recent Neisseria gonorrhoeae infection (HR 3.3 95% CI 1.5–7.4) were significantly associated with increased risk of acquiring C. trachomatis infection.
The high incidence of C. trachomatis among younger high-risk women suggests the need for screening as an important public health intervention for this population.
PMCID: PMC3831875  PMID: 23407467
Chlamydia trachomatis; incidence; risk factors; women; Africa
21.  Incident HIV during Pregnancy and Postpartum and Risk of Mother-to-Child HIV Transmission: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(2):e1001608.
Alison Drake and colleagues conduct a systematic review and meta-analysis to estimate maternal HIV incidence during pregnancy and the postpartum period and to compare mother-to-child HIV transmission risk among women with incident versus chronic infection.
Please see later in the article for the Editors' Summary
Women may have persistent risk of HIV acquisition during pregnancy and postpartum. Estimating risk of HIV during these periods is important to inform optimal prevention approaches. We performed a systematic review and meta-analysis to estimate maternal HIV incidence during pregnancy/postpartum and to compare mother-to-child HIV transmission (MTCT) risk among women with incident versus chronic infection.
Methods and Findings
We searched PubMed, Embase, and AIDS-related conference abstracts between January 1, 1980, and October 31, 2013, for articles and abstracts describing HIV acquisition during pregnancy/postpartum. The inclusion criterion was studies with data on recent HIV during pregnancy/postpartum. Random effects models were constructed to pool HIV incidence rates, cumulative HIV incidence, hazard ratios (HRs), or odds ratios (ORs) summarizing the association between pregnancy/postpartum status and HIV incidence, and MTCT risk and rates. Overall, 1,176 studies met the search criteria, of which 78 met the inclusion criterion, and 47 contributed data. Using data from 19 cohorts representing 22,803 total person-years, the pooled HIV incidence rate during pregnancy/postpartum was 3.8/100 person-years (95% CI 3.0–4.6): 4.7/100 person-years during pregnancy and 2.9/100 person-years postpartum (p = 0.18). Pooled cumulative HIV incidence was significantly higher in African than non-African countries (3.6% versus 0.3%, respectively; p<0.001). Risk of HIV was not significantly higher among pregnant (HR 1.3, 95% CI 0.5–2.1) or postpartum women (HR 1.1, 95% CI 0.6–1.6) than among non-pregnant/non-postpartum women in five studies with available data. In African cohorts, MTCT risk was significantly higher among women with incident versus chronic HIV infection in the postpartum period (OR 2.9, 95% CI 2.2–3.9) or in pregnancy/postpartum periods combined (OR 2.3, 95% CI 1.2–4.4). However, the small number of studies limited power to detect associations and sources of heterogeneity.
Pregnancy and the postpartum period are times of persistent HIV risk, at rates similar to “high risk” cohorts. MTCT risk was elevated among women with incident infections. Detection and prevention of incident HIV in pregnancy/postpartum should be prioritized, and is critical to decrease MTCT.
Please see later in the article for the Editors' Summary
Editors' Summary
Worldwide, about 3.4 million children younger than 15 years old (mostly living in sub-Saharan Africa) are infected with HIV, the virus that causes AIDS by gradually destroying immune system cells, thereby leaving infected individuals susceptible to other serious infections. In 2012 alone, 230,000 children (more than 700 every day) were newly infected with HIV. Most HIV infections among children are the result of mother-to-child HIV transmission (MTCT) during pregnancy, delivery, or breastfeeding. The rate of MTCT (and deaths among HIV-positive pregnant women from complications related to HIV infection) can be greatly reduced by testing women for HIV infection during pregnancy (antenatal HIV testing), treating HIV-positive women with antiretroviral drugs (ARVs, powerful drugs that control HIV replication and allow the immune system to recover) during pregnancy, delivery, and breastfeeding, and giving ARVs to their newborn babies.
Why Was This Study Done?
The World Health Organization and the Joint United Nations Programme on HIV/AIDS (UNAIDS) have developed a global plan that aims to move towards eliminating new HIV infections among children by 2015 and towards keeping their mothers alive. To ensure the plan's success, the incidence of HIV (the number of new infections) among women and the rate of MTCT must be reduced by increasing ARV uptake by mothers and their infants for the prevention of MTCT. However, the risk of HIV infection among pregnant women and among women who have recently given birth (postpartum women) is poorly understood because, although guidelines recommend repeat HIV testing during late pregnancy or at delivery in settings where HIV infection is common, pregnant women are often tested only once for HIV infection. The lack of retesting represents a missed opportunity to identify pregnant and postpartum women who have recently acquired HIV and to prevent MTCT by initiating ARV therapy. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic) and meta-analysis (a study that uses statistical methods to combine the results of several studies), the researchers estimate maternal HIV incidence during pregnancy and the postpartum period, and compare the risk of MTCT among women with incident (new) and chronic (long-standing) HIV infection.
What Did the Researchers Do and Find?
The researchers identified 47 studies (35 undertaken in Africa) that examined recent HIV acquisition by women during pregnancy and the 12-month postpartum period. They used random effects statistical models to estimate the pooled HIV incidence rate and cumulative HIV incidence (the number of new infections per number of people at risk), and the association between pregnancy/postpartum status and HIV incidence and MTCT risk and rates. The pooled HIV incidence rate among pregnant/postpartum women estimated from 19 studies (all from sub-Saharan Africa) that reported HIV incidence rates was 3.8/100 person-years. The pooled cumulative HIV incidence was significantly higher in African countries than in non-African countries (3.6% and 0.3%, respectively; a “significant” difference is one that is unlikely to arise by chance). In the five studies that provided suitable data, the risk of HIV acquisition was similar in pregnant, postpartum, and non-pregnant/non-postpartum women. Finally, among African women, the risk of MTCT was 2.9-fold higher during the postpartum period among those who had recently acquired HIV than among those with chronic HIV infection, and 2.3-fold higher during the pregnancy/postpartum periods combined.
What Do These Findings Mean?
These results suggest that women living in regions where HIV infection is common are at high risk of acquiring HIV infection during pregnancy and the postpartum period and that mothers who acquire HIV during pregnancy or postpartum are more likely to pass the infection on to their offspring than mothers with chronic HIV infections. However, the small number of studies included in this meta-analysis and the use of heterogeneous research methodologies in these studies may limit the accuracy of these findings. Nevertheless, these findings have important implications for the global plan to eliminate HIV infections in children. First, they suggest that women living in regions where HIV infection is common should be offered repeat HIV testing (using sensitive methods to enhance early detection of infection) during pregnancy and in the postpartum period to detect incident HIV infections, and should be promptly referred to HIV care and treatment. Second, they suggest that prevention of HIV transmission during pregnancy and postpartum should be prioritized, for example, by counseling women about the need to use condoms to prevent transmission during this period of their lives.
Additional Information
Please access these websites via the online version of this summary at
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on children and HIV/AIDS and on the prevention of mother-to-child transmission of HIV (in English and Spanish)
The 2013 UNAIDS World AIDS Day Report provides information about the AIDS epidemic and efforts to halt it; the 2013 UNAIDS Progress Report on the Global Plan provides information on progress towards eliminating new HIV infections among children; the UNAIDS Believe it. Do it website provides information about the campaign to support the UNAIDS global plan
Personal stories about living with HIV/AIDS, including stories from young people infected with HIV, are available through Avert, NAM/aidsmap, and Healthtalkonline
PMCID: PMC3934828  PMID: 24586123
22.  Maternal Valacyclovir and Infant Cytomegalovirus Acquisition: A Randomized Controlled Trial among HIV-Infected Women 
PLoS ONE  2014;9(2):e87855.
Studies in HIV-1-infected infants and HIV-1-exposed, uninfected infants link early cytomegalovirus (CMV) acquisition with growth delay and cognitive impairment. We investigated maternal valacyclovir to delay infant acquisition of CMV.
Pregnant women with HIV-1, HSV-2 and CD4 count >250 cells/µl were randomized at 34 weeks gestation to 500 mg twice-daily valacyclovir or placebo for 12 months. Maternal CMV DNA was measured in plasma at 34 weeks gestation, in cervical secretions at 34 and 38 weeks gestation, and in breast milk at 7 postpartum timepoints; infant CMV DNA was measured in dried blood spots at 8 timepoints including birth.
Among 148 women, 141 infants were compared in intent-to-treat analyses. Maternal and infant characteristics were similar between study arms. Infant CMV acquisition did not differ between study arms, with 46/70 infants (66%) in placebo arm and 47/71 infants (66%) in the valacyclovir arm acquiring CMV; median time to CMV detection did not differ. CMV DNA was detected in 92% of 542 breast milk specimens with no difference in CMV level between study arms. Change in cervical shedding of CMV DNA between baseline and 38 weeks was 0.40-log greater in the placebo arm than the valacyclovir arm (p = 0.05).
In this cohort of HIV-1-seropositive mothers, two-thirds of infants acquired CMV by one year. Maternal valacyclovir had no effect on timing of infant CMV acquisition or breast milk CMV viral loads, although it modestly reduced cervical CMV shedding. Maternal prophylaxis to reduce infant CMV acquisition warrants further evaluation in trials with antiviral agents.
Trials Registration NCT00530777
PMCID: PMC3913686  PMID: 24504006
23.  Adherence and acceptability in MTN 001: A randomized cross-over trial of daily oral and topical tenofovir for HIV prevention in women 
AIDS and behavior  2013;17(2):737-747.
We compared adherence to and acceptability of daily topical and oral formulations of tenofovir (TFV) used as pre-exposure prophylaxis (PrEP) for HIV prevention among women in South Africa, Uganda and the United States. 144 sexually active, HIV-uninfected women participated in a cross-over study of three regimens: oral tablet, vaginal gel, or both. We tested for differences in adherence and evaluated product acceptability. Self-reported adherence for all regimens was high (94%), but serum TFV concentrations indicated only 64% of participants used tablets consistently. Most women in the U.S. (72%) favored tablets over gel; while preferences varied at the African sites (42% preferred gel and 40% tablets). Findings indicate a role for oral and vaginal PrEP formulations and highlight the importance of integrating pharmacokinetics-based adherence assessment in future trials. Biomedical HIV prevention interventions should consider geographic and cultural experience with product formulations, partner involvement, and sexual health benefits that ultimately influence use.
PMCID: PMC3562423  PMID: 23065145
anti-infective agents; HIV; patient compliance; sexual behavior; vaginal creams, foams and jellies; administration, oral; PrEP; microbicide
24.  A Prospective Study of Risk Factors for Bacterial Vaginosis in HIV-1-Seronegative African Women 
Sexually transmitted diseases  2008;35(6):617-623.
Bacterial vaginosis (BV) is common and has been associated with increased HIV-1 susceptibility. The objective of this study was to identify risk factors for BV in African women at high risk for acquiring HIV-1.
We conducted a prospective study among 151 HIV-1-seronegative Kenyan female sex workers. Non-pregnant women were eligible if they did not have symptoms of abnormal vaginal itching or discharge at the time of enrollment. At monthly follow-up, a vaginal examination and laboratory testing for genital tract infections were performed. Multivariate Andersen-Gill proportional hazards analysis was used to identify correlates of BV.
Participants completed a median of 378 (interquartile range 350–412) days of follow-up. Compared to women reporting no vaginal washing, those who reported vaginal washing 1–14 (adjusted hazard ratio [aHR] 1.29, 95% confidence interval [CI] 0.88–1.89), 15–28 (aHR 1.60, 95% CI 0.98–2.61), and >28 times/week (aHR 2.39, 95% CI 1.35–4.23) were at increased risk of BV. Higher BV incidence was also associated with the use of cloth for intravaginal cleansing (aHR 1.48, 95% CI 1.06–2.08) and with recent unprotected intercourse (aHR 1.75, 95% CI 1.47–2.08). Women using depot medroxyprogesterone acetate contraception were at lower risk for BV (aHR 0.59, 95% CI 0.48–0.73).
Vaginal washing and unprotected intercourse were associated with increased risk of BV. These findings could help to inform the development of novel vaginal health approaches for HIV-1 risk reduction in women.
PMCID: PMC3902781  PMID: 18418290
Bacterial vaginosis; vaginal washing; intravaginal practices; women; Africa
25.  Correlates and outcomes of preterm birth, low birth weight, and small for gestational age in HIV-exposed uninfected infants 
Preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) contribute to neonatal mortality. Maternal HIV-1 infection has been associated with an increased risk of PTB, but mechanisms underlying this association are undefined. We describe correlates and outcomes of PTB, LBW, and SGA in HIV-exposed uninfected infants.
This was a retrospective analysis of cohort study. Between 1999–2002, pregnant, HIV-infected women were enrolled into an HIV-1 transmission study. Logistic regression was used to identify correlates of PTB, LBW and SGA in HIV-negative, spontaneous singleton deliveries. Associations between birth outcomes and mortality were measured using survival analyses.
In multivariable models, maternal plasma (OR = 2.1, 95% CI = 1.1-3.8) and cervical HIV-1 RNA levels (OR = 1.6, 95% CI = 1.1-2.4), and CD4 < 15% (OR = 2.4, 95% CI = 1.0-5.6) were associated with increased odds of PTB. Abnormal vaginal discharge and cervical polymorphonuclear leukocytes were also associated with PTB. Cervical HIV-1 RNA level (OR = 2.4, 95% CI = 1.5-6.7) was associated with an increased odds of LBW, while increasing parity (OR = 0.46, 95% CI = 0.24-0.88) was associated with reduced odds. Higher maternal body mass index (OR = 0.75, 95% CI = 0.61-0.92) was associated with a reduced odds of SGA, while bacterial vaginosis was associated with >3-fold increased odds (OR = 3.2, 95% CI = 1.4-7.4). PTB, LBW, and SGA were each associated with a >6-fold increased risk of neonatal death, and a >2-fold increased rate of infant mortality within the first year.
Maternal plasma and cervical HIV-1 RNA load, and genital infections may be important risk factors for PTB in HIV-exposed uninfected infants. PTB, LBW, and SGA are associated with increased neonatal and infant mortality in HIV-exposed uninfected infants.
PMCID: PMC3897882  PMID: 24397463
Preterm birth; Low birth weight; Small for gestational age; Pediatric HIV

Results 1-25 (143)