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1.  Short Communication: T Cell Activation in HIV-1/Herpes Simplex Virus-2-Coinfected Kenyan Women Receiving Valacyclovir 
Abstract
Herpes simplex virus-2 (HSV-2) suppression with acyclovir or valacyclovir reduces HIV-1 viral RNA levels; one hypothesis is that HSV-2 suppression reduces immune activation. We measured T cell immune activation markers among women participating in a randomized placebo-controlled trial of valacyclovir to reduce HIV-1 RNA levels among pregnant women. Although valacyclovir was associated with lower HIV-1 RNA levels, the distribution of both CD4+ and CD8+ CD38+HLA-DR+ T cells was not different among women taking valacyclovir when compared to women taking placebo. Further study is needed to understand the mechanism of HIV-1 RNA reduction following herpes suppression among those coinfected with HIV-1 and HSV-2.
doi:10.1089/aid.2012.0071
PMCID: PMC3537320  PMID: 22852760
3.  Subtype C Is Associated with Increased Vaginal Shedding of HIV-1 
The Journal of Infectious Diseases  2005;192(3):492-496.
The prevalence of human immunodeficiency virus (HIV)–1–infected cells and HIV-1 RNA levels in genital secretions and breast milk and the risk of mother-to-child transmission of HIV-1 were compared among subtypes A, C, and D in a Kenyan cohort. Pregnant women infected with subtype C were significantly more likely to shed HIV-1-infected vaginal cells than were those infected with subtype A or D (odds ratio [OR], 3.6 [95% confidence interval {CI}, 1.4–8.8]; P = .006). This relationship held after adjusting for age, CD4 cell count, and plasma HIV-1 RNA load (OR, 3.1 [95% CI, 1.1–8.6]; P = .03). These observations suggest that HIV-1 subtype influences mucosal shedding of HIV-1.
doi:10.1086/431514
PMCID: PMC3387274  PMID: 15995964
4.  Infant feeding and prevention of mother-to-child transmission of HIV-1 
Current Opinion in HIV and AIDS  2008;3(2):173-179.
Purpose of review
To review new studies and directions regarding infant feeding and HIV-1 transmission.
Recent findings
With antiretroviral drugs and shortened breastfeeding, breast milk HIV-1 transmission risk can be decreased from 16 to less than 5%. In the context of peripartum antiretroviral drugs/short breastfeeding, replacement feeding provides negligible benefit in decreasing the risk of HIV-1/death in contrast to previous studies of no antiretroviral drugs/unlimited breastfeeding in which it offered benefit. One study noted a high risk of infant HIV-1 or death (≥17%) after 4 months, with no difference in risk in infants with shortened breastfeeding versus indefinite breastfeeding. This study suggests that shortened breastfeeding needs caution in implementation. Other African studies have noted minimal risk of HIV-1 or death (<2%) after shortened breastfeeding, underscoring the heterogeneity of infant survival in different settings and the potential to improve infant survival.
Summary
Antiretroviral drugs and shortened breastfeeding markedly decrease breastfeeding HIV-1 transmission, shifting the balance to make replacement feeding less beneficial. In some settings shortened breastfeeding poses similar risks as replacement feeding and provides no infant health benefit compared with extended breastfeeding. Programmes aimed at decreasing infant HIV-1 need to do so in the context of promoting infant survival. Strengthening systems to promote infant health is critical.
doi:10.1097/COH.0b013e3282f50bc6
PMCID: PMC3373175  PMID: 19372962
breastfeeding; HAART; replacement feeding
5.  Male, Mobile, and Moneyed: Loss to Follow-Up vs. Transfer of Care in an Urban African Antiretroviral Treatment Clinic 
PLoS ONE  2013;8(10):e78900.
Objectives
The purpose of this study was to analyze characteristics, reasons for transferring, and reasons for discontinuing care among patients defined as lost to follow-up (LTFU) from an antiretroviral therapy (ART) clinic in Nairobi, Kenya.
Design
The study used a prospective cohort of patients who participated in a randomized, controlled ART adherence trial between 2006 and 2008.
Methods
Participants were followed from pre-ART clinic enrollment to 18 months after ART initiation, and were defined as LTFU if they failed to return to clinic 4 weeks after their last scheduled visit. Reasons for loss were captured through phone call or home visit. Characteristics of LTFU who transferred care and LTFU who did not transfer were compared to those who remained in clinic using log-binomial regression to estimate risk ratios.
Results
Of 393 enrolled participants, total attrition was 83 (21%), of whom 75 (90%) were successfully traced. Thirty-seven (49%) were alive at tracing and 22 (59%) of these reported having transferred their antiretroviral care. In the final model, transfers were more likely to have salaried employment [Risk Ratio (RR), 2.7; 95% confidence interval (CI), 1.2-6.1; p=0.020)] and pay a higher monthly rent (RR, 5.8; 95% CI, 1.3-25.0; p=0.018) compared to those retained in clinic. LTFU who did not transfer care were three times as likely to be men (RR, 3.1; 95% CI, 1.1-8.1; p=0.028) and nearly 4 times as likely to have a primary education or less (RR, 3.8; 95% CI, 1.3-10.6; p=0.013). Overall, the most common reason for LTFU was moving residence, predominantly due to job loss or change in employment.
Conclusion
A broad definition of LTFU may include those who have transferred their antiretroviral care and thereby overestimate negative effects on ART continuation. Interventions targeting men and considering mobility due to employment may improve retention in urban African ART clinics.
Clinical Trials
The study’s ClinicalTrials.gov identifier is NCT00273780.
doi:10.1371/journal.pone.0078900
PMCID: PMC3812001  PMID: 24205345
6.  A Phase I Randomized Clinical Trial of Candidate Human Immunodeficiency Virus type 1 Vaccine MVA.HIVA Administered to Gambian Infants 
PLoS ONE  2013;8(10):e78289.
Background
A vaccine to decrease transmission of human immunodeficiency virus type 1 (HIV-1) during breast-feeding would complement efforts to eliminate infant HIV-1 infection by antiretroviral therapy. Relative to adults, infants have distinct immune development, potentially high-risk of transmission when exposed to HIV-1 and rapid progression to AIDS when infected. To date, there have been only three published HIV-1 vaccine trials in infants.
Trial Design
We conducted a randomized phase I clinical trial PedVacc 001 assessing the feasibility, safety and immunogenicity of a single dose of candidate vaccine MVA.HIVA administered intramuscularly to 20-week-old infants born to HIV-1-negative mothers in The Gambia.
Methods
Infants were followed to 9 months of age with assessment of safety, immunogenicity and interference with Expanded Program on Immunization (EPI) vaccines. The trial is the first stage of developing more complex prime-boost vaccination strategies against breast milk transmission of HIV-1.
Results
From March to October 2010, 48 infants (24 vaccine and 24 no-treatment) were enrolled with 100% retention. The MVA.HIVA vaccine was safe with no difference in adverse events between vaccinees and untreated infants. Two vaccine recipients (9%) and no controls had positive ex vivo interferon-γ ELISPOT assay responses. Antibody levels elicited to the EPI vaccines, which included diphtheria, tetanus, whole-cell pertussis, hepatitis B virus, Haemophilus influenzae type b and oral poliovirus, reached protective levels for the vast majority and were similar between the two arms.
Conclusions
A single low-dose of MVA.HIVA administered to 20-week-old infants in The Gambia was found to be safe and without interference with the induction of protective antibody levels by EPI vaccines, but did not alone induce sufficient HIV-1-specific responses. These data support the use of MVA carrying other transgenes as a boosting vector within more complex prime-boost vaccine strategies against transmission of HIV-1 and/or other infections in this age group.
Trial Registration
ClinicalTrials.gov NCT00982579
The Pan African Clinical Trials Registry PACTR2008120000904116
doi:10.1371/journal.pone.0078289
PMCID: PMC3813444  PMID: 24205185
7.  Survival Benefit of Early Infant Antiretroviral Therapy is Compromised when Diagnosis is Delayed 
Late presentation is common among African HIV-1-infected infants. Incidence and correlates of mortality were examined in 99 infants with HIV-1 diagnosis by age 5 months. Twelve-month survival was 66.8% (95% confidence interval, 55.9%, 75.6%). WHO stage 3/4, underweight, wasting, microcephaly, low hemoglobin, pneumonia, and gastroenteritis predicted mortality. Early HIV-1 diagnosis with ART before symptomatic disease is critical for infant survival.
doi:10.1097/INF.0b013e3182587796
PMCID: PMC3756892  PMID: 22544051
Pediatric; Infant; HIV-1; Antiretroviral therapy; Mortality
8.  Increased incidence of symptomatic peripheral neuropathy among adults receiving stavudine- versus zidovudine-based antiretroviral regimens in Kenya 
Journal of neurovirology  2012;18(3):200-204.
The incidence of peripheral neuropathy (PN) among adults initiating antiretroviral therapy (ART) containing stavudine (d4T) versus zidovudine (ZDV) is not well described. We compared 1-year incidence between d4T- and ZDV-based regimens in adults initiating ART in a programmatic setting in Kenya. Of 1,848 adults on ART, 1,579 (85 %) initiated d4T-based and 269 (15 %) initiated ZDV-based regimens. One-year incidence of symptomatic PN per 100 person-years was 21.9 (n=236) among d4T users and 6.9 (n=7) among ZDV users (P=0.0002). D4T was associated with 2.7 greater risk of PN than ZDV (adjusted hazard ratio, 2.7, P=0.009). In settings with continued d4T use, such as Africa, the effects of d4T on PN compared to ZDV should be considered when choosing ART regimens.
doi:10.1007/s13365-012-0098-x
PMCID: PMC3726537  PMID: 22528481
Peripheral neuropathy; Africa; Antiretroviral therapy; Toxicity; HIV
9.  Domestic violence and prevention of mother-to-child transmission of HIV-1 
AIDS (London, England)  2006;20(13):1763-1769.
Objectives
To determine the prevalence of life-time domestic violence by the current partner before HIV-1 testing, its impact on the uptake of prevention of mother-to-child transmission (PMTCT) interventions and frequency after testing.
Design
A prospective cohort.
Methods
Antenatally, women and their partners were interviewed regarding physical, financial, and psychological abuse by the male partner before HIV-1 testing and 2 weeks after receiving results.
Results
Before testing, 804 of 2836 women (28%) reported previous domestic violence, which tended to be associated with increased odds of HIV-1 infection [univariate odds ratio (OR) 1.7, 95% confidence interval (CI) 1.3–2.2; P < 0.0001, adjusted OR 1.2, 95% CI 0.9–1.6; P = 0.1], decreased odds of coming with partners for counseling (adjusted OR 0.7, 95% CI 0.5–1.0; P = 0.04), and decreased odds of partner notification (adjusted OR 0.7, 95% CI 0.5–1.1; P = 0.09). Previous domestic violence was not associated with a reduced uptake of HIV-1 counseling, HIV-1 testing, or nevirapine. After receiving results, 15 out of 1638 women (0.9%) reported domestic violence. After notifying partners of results, the odds of HIV-1-seropositive women reporting domestic violence were 4.8 times those of HIV-1-seronegative women (95% CI 1.4–16; P = 0.01). Compared with women, men reported similar or more male-perpetrated domestic violence, suggesting a cultural acceptability of violence.
Conclusion
Domestic violence before testing may limit partner involvement in PMTCT. Although infrequent, immediate post-test domestic violence is more common among HIV-1-infected than uninfected women. Domestic violence prevention programmes need to be integrated into PMTCT, particularly for HIV-1-seropositive women.
doi:10.1097/01.aids.0000242823.51754.0c
PMCID: PMC3384736  PMID: 16931941
Adverse effects; Africa; domestic violence; HIV; vertical transmission; prevention of mother-to-child transmission
10.  The effect of rapid HIV-1 testing on uptake of perinatal HIV-1 interventions: a randomized clinical trial 
AIDS (London, England)  2003;17(1):113-118.
Objective
We examined whether HIV-1 testing using a rapid assay increases the proportion of pregnant women obtaining HIV-1 results and the uptake of perinatal HIV-1 interventions.
Methods
Pregnant women attending public health clinics in Nairobi were offered voluntary counselling and testing for HIV-1. Consenting women were randomly assigned to receive either rapid or conventional HIV-1 testing. Women randomly assigned to rapid testing were allowed to receive same-day results or to return later. The results for women randomly assigned to conventional enzyme-linked immunosorbent assay (ELISA) testing were available after 7 days. HIV-1-infected women were referred for antiretroviral prophylaxis to prevent mother-to-child transmission of HIV-1.
Results
Among 1282 women offered voluntary HIV-1 testing and counselling, 1249 accepted testing, of whom 627 were randomly assigned to rapid testing and 622 to conventional testing. The median duration between testing and obtaining results was 0 days for women who received rapid testing compared with 11 days for women who received conventional testing. The percentage receiving HIV-1 results was significantly higher among women who received rapid testing compared with conventional testing. Of 161 HIV-1-seropositive women, only 24 received antiretroviral prophylaxis. The uptake of perinatal HIV-1 interventions did not differ between HIV-1-seropositive women randomly assigned to rapid testing or conventional ELISA testing.
Conclusion
Rapid HIV-1 testing significantly increased the proportion of women receiving HIV-1 results, which is important for sexual and perinatal HIV-1 prevention. The challenge remains to improve the uptake of perinatal HIV-1 interventions among HIV-1-seropositive women.
doi:10.1097/01.aids.0000042934.55529.de
PMCID: PMC3380077  PMID: 12478076
Africa; perinatal HIV interventions; prevention of mother-to-child transmission of HIV; randomized clinical trial; rapid HIV testing; voluntary counselling and testing
11.  When Is Replacement Feeding Safe for Infants of HIV-Infected Women? 
PLoS Medicine  2007;4(1):e30.
doi:10.1371/journal.pmed.0040030
PMCID: PMC1769417  PMID: 17227137
12.  Acute Cytomegalovirus Infection Is Associated with Increased Frequencies of Activated and Apoptosis-Vulnerable T Cells in HIV-1-Infected Infants 
Journal of Virology  2012;86(20):11373-11379.
Cytomegalovirus (CMV) coinfection is associated with infant HIV-1 disease progression and mortality. In a cohort of Kenyan HIV-infected infants, the frequencies of activated (CD38+ HLA-DR+) and apoptosis-vulnerable (CD95+ Bcl-2−) CD4+ and CD8+ T cells increased substantially during acute CMV infection. The frequency of activated CD4+ T cells was strongly associated with both concurrent CMV coinfection (P = 0.001) and HIV-1 viral load (P = 0.05). The frequency of apoptosis-vulnerable cells was also associated with CMV coinfection in the CD4 (P = 0.02) and CD8 (P < 0.001) T cell subsets. Similar observations were made in HIV-exposed uninfected infants. CMV-induced increases in T cell activation and apoptosis may contribute to the rapid disease progression in coinfected infants.
doi:10.1128/JVI.00790-12
PMCID: PMC3457128  PMID: 22875969
13.  Knowing a Sexual Partner Is HIV-1-Uninfected Is Associated With Higher Condom Use Among HIV-1-Infected Adults in Kenya 
Sexually Transmitted Diseases  2011;38(9):808-810.
The relation between awareness of sexual partner’s HIV serostatus and unprotected sex was examined in HIV clinic enrollees. Increased condom use was associated with knowing that a partner was HIV-negative (adjusted odds ratio = 5.99; P < 0.001) versus not knowing partner’s status. Partner testing may increase condom use in discordant couples.
doi:10.1097/OLQ.0b013e31821c3713
PMCID: PMC3404889  PMID: 21844734
14.  HIV-1 Disease Progression in Breast-Feeding and Formula-Feeding Mothers: A Prospective 2-Year Comparison of T Cell Subsets, HIV-1 RNA Levels, and Mortality 
The Journal of Infectious Diseases  2006;195(2):220-229.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1086/510245
PMCID: PMC3394541  PMID: 17191167
15.  Compliance with antiretroviral regimens to prevent perinatal HIV-1 transmission in Kenya 
AIDS (London, England)  2003;17(1):65-71.
Objective
To compare compliance and infant HIV-1 infection risk at 6 weeks with the Thai-CDC and HIVNET-012 antiretroviral regimens in a field setting.
Design
Randomized clinical trial.
Setting
Tertiary hospital antenatal clinic in Nairobi, Kenya.
Participants
HIV-1 infected women referred from primary care clinics.
Interventions
Thai-CDC zidovudine regimen or HIVNET-012 nevirapine regimen.
Main outcome measures
Women were considered compliant if they used ≥ 80% of the doses. Infants were tested for HIV-1 at 6 weeks.
Results
Seventy women were randomized to Thai-CDC and 69 to HIVNET-012 regimens. More women were compliant with the antenatal (86%) than the intrapartum (44%) Thai-CDC regimen doses (P = 0.001). Ninety-seven per cent took the maternal and 91% gave the infant dose of the HIVNET-012 regimen (P = 0.2). Overall, 41% were compliant with the Thai-CDC regimen and 87% with the HIVNET-012 regimen (P < 0.001). Compliance with the Thai-CDC regimen was associated with partner support of antiretroviral use [odds ratio (OR), 3.0;, 95% confidence interval (CI), 1.0–9.1] and knowledge at recruitment that antiretroviral drugs could prevent infant HIV-1 (OR, 2.9; 95% CI, 1.0–8.1). Compliance with the HIVNET-012 regimen was associated with partner notification (OR, 8.0; 95% CI, 1.5–50) and partner willingness to have HIV-1 testing (OR, 7.5; 95% CI, 1.4–40). There was a trend for a higher risk of transmission with the HIVNET-012 regimen than with the Thai-CDC regimen (22% versus 9%; P = 0.07).
Conclusion
Compliance with the Thai-CDC and HIVNET-012 regimens was comparable to that in efficacy trials. Partner involvement, support and education on perinatal HIV-1 prevention may improve compliance and increase the number of infants protected from HIV-1 infection.
doi:10.1097/01.aids.0000042938.55529.e1
PMCID: PMC3387271  PMID: 12478070
antiretroviral therapy; vertical transmission; compliance; prevention of perinatal transmission
16.  Longitudinal Analysis of Human Immunodeficiency Virus Type 1 RNA in Breast Milk and of Its Relationship to Infant Infection and Maternal Disease 
The Journal of Infectious Diseases  2003;187(5):741-747.
Transmission of human immunodeficiency virus type 1 (HIV-1) via breast-feeding can occur throughout lactation. Defining both fluctuation in breast-milk virus level over time and how breast-milk virus correlates with mother-to-child transmission is important for establishing effective interventions. We quantified breast-milk HIV-1 RNA levels in serial samples collected from 275 women for up to 2 years after delivery. Higher maternal plasma virus load, lower maternal CD4 T cell count, and detection of HIV-1 DNA in maternal genital secretions were significantly associated with elevated breast-milk HIV-1 RNA. Within women who breast-fed, median virus load in colostrum/early milk was significantly higher than that in mature breast milk collected 14 days after delivery (P ≤ .004). Breast-feeding mothers who transmitted HIV-1 to their infants had both significantly higher breast-milk viral RNA throughout lactation and more-consistent viral shedding, compared with mothers who did not transmit HIV-1. In breast-feeding women, a 2-fold-increased risk of transmission was associated with every 10-fold increase in breast-milk virus load (95% confidence interval, 1.3–3.0; P < .001). These results indicate that the risk of infant infection from breast-feeding is influenced by breast-milk virus load, which is highest early after delivery.
doi:10.1086/374273
PMCID: PMC3384731  PMID: 12599047
17.  Antenatal Couple Counseling Increases Uptake of Interventions to Prevent HIV-1 Transmission 
Summary
To determine effect of partner involvement and couple counseling on uptake of interventions to prevent HIV-1 transmission, women attending a Nairobi antenatal clinic were encouraged to return with partners for voluntary HIV-1 counseling and testing (VCT) and offered individual or couple posttest counseling. Nevirapine was provided to HIV-1-seropositive women and condoms distributed to all participants. Among 2104 women accepting testing, 308 (15%) had partners participate in VCT, of whom 116 (38%) were couple counseled. Thirty-two (10%) of 314 HIV-1-seropositive women came with partners for VCT; these women were 3-fold more likely to return for nevirapine (P = 0.02) and to report administering nevirapine at delivery (P = 0.009). Nevirapine use was reported by 88% of HIV-infected women who were couple counseled, 67% whose partners came but were not couple counseled, and 45% whose partners did not present for VCT (P for trend = 0.006). HIV-1-seropositive women receiving couple counseling were 5-fold more likely to avoid breast-feeding (P = 0.03) compared with those counseled individually. Partner notification of HIV-1-positive results was reported by 138 women (64%) and was associated with 4-fold greater likelihood of condom use (P = 0.004). Partner participation in VCT and couple counseling increased uptake of nevirapine and formula feeding. Antenatal couple counseling may be a useful strategy to promote HIV-1 prevention interventions.
PMCID: PMC3384734  PMID: 15577420
voluntary counseling and testing; couple counseling; mother-to-child HIV-1 transmission; breastfeeding; nevirapine; condom use; partner notification
18.  Association of Levels of HIV-1–Infected Breast Milk Cells and Risk of Mother-to-Child Transmission 
The Journal of Infectious Diseases  2004;190(10):1880-1888.
Understanding how the level of human immunodeficiency virus type 1 (HIV-1)–infected breast milk cells (BMCs) affects HIV transmission via breast-feeding can shed light on the mechanism of infection and aid in establishing effective interventions. The proportion of infected cells to total cells was measured in serial breast milk samples collected from 291 HIV-1–infected women in Nairobi, Kenya, by use of real-time DNA polymerase chain reaction amplification of BMCs. The number of infected BMCs per million cells was associated with levels of cell-free viral RNA in breast milk (R = .144; P = .032), levels of cell-free virus in blood plasma (R = .365; P < .001), and the detection of proviral DNA in cervical and vaginal secretions (P < .001 and P = .030, respectively). The number of infected BMCs per million cells was lower in colostrum or early milk than in mature milk (P < .001). Previous studies demonstrated that the concentration of BMCs varies throughout lactation, and we used these data to transform infected BMCs per million cells to infected BMCs per milliliter. The estimated concentration of infected BMCs per milliliter was higher in colostrum or early milk than in mature milk (P < .001). Each log10 increase in infected BMCs per milliliter was associated with a 3.19-fold–increased risk of transmission (P = 002), after adjustment for cell-free virus in plasma (hazard ratio [HR], 2.09; P = 03) and breast milk (HR, 1.01; P = 1.00). This suggests that infected BMCs may play a more important role in transmission of HIV via breast-feeding than does cell-free virus.
doi:10.1086/425076
PMCID: PMC3384735  PMID: 15499546
19.  Implementation of free cotrimoxazole prophylaxis improves clinic retention among antiretroviral therapy-ineligible clients in Kenya 
AIDS (London, England)  2011;25(13):1657-1661.
Objective
To determine whether implementation of free cotrimoxazole (CTX) provision was associated with improved retention among clients ineligible for antiretroviral therapy (ART) enrolled in an HIV treatment program in Kenya.
Design
Data were obtained from a clinical cohort for program evaluation purposes. Twelve-month clinic retention was compared among ART-ineligible clients enrolled in the time period before free CTX versus the time period after.
Methods
Statistical comparisons were made using Kaplan–Meier survival curves, log-rank tests, and multivariate Cox proportional hazards models. To exclude potential temporal program changes that may have influenced retention, ART clients before and after the same cut-off date were compared.
Findings
Among adult clients enrolled between 2005 and 2007, 3234 began ART within 1 year of enrollment, and 1024 of those who did not start treatment were defined as ART-ineligible. ART-ineligible clients enrolled in the period following free CTX provision had higher 12-month retention (84%) than those who enrolled prior to free CTX (63%; P < 0.001). Retention did not change significantly during these periods among ART clients (P = 0.55). In multivariate analysis, ART-ineligible clients enrolled prior to free CTX were more than twice as likely to be lost to follow-up compared to those following free CTX [adjusted hazard ratio (aHR) = 2.64, 95% confidence interval 1.95–3.57, P < 0.001].
Conclusion
Provision of free CTX was associated with significantly improved retention among ART-ineligible clients. Retention and CD4-monitoring of ART-ineligible clients are essential to promptly identify ART eligibility and provide treatment. Implementation of free CTX may improve retention in sub-Saharan Africa and, via increasing timely ART initiation, provide survival benefit.
doi:10.1097/QAD.0b013e32834957fd
PMCID: PMC3383052  PMID: 21673562
antibiotic; HIV; lost to follow-up; prophylaxis; trimethoprim–sulfamethoxazole combination
20.  Salivary Secretory Leukocyte Protease Inhibitor Is Associated with Reduced Transmission of Human Immunodeficiency Virus Type 1 through Breast Milk 
The Journal of Infectious Diseases  2002;186(8):1173-1176.
Secretory leukocyte protease inhibitor (SLPI), a protein found in saliva, breast milk, and genital secretions, is capable of inhibiting human immunodeficiency virus (HIV) type 1 in vitro. The aim of this study was to determine whether SLPI in infant saliva provides protection against mother-to-child HIV-1 transmission. In total, 602 saliva specimens were collected from 188 infants at birth and at ages 1, 3, and 6 months. Infants’ median salivary SLPI concentrations were higher at birth than at 6 months (341 vs. 219 ng/mL; P = .001). There was no association between SLPI concentration and HIV-1 transmission overall. However, among 122 breast-fed infants who were HIV-1 uninfected at 1 month, higher salivary SLPI levels were associated with a decreased risk of HIV-1 transmission through breast milk (hazard ratio, 0.5; 95% confidence interval, 0.3–0.9; P = .03). These results suggest that SLPI plays an important role in reducing HIV-1 transmission through breast milk.
doi:10.1086/343805
PMCID: PMC3382060  PMID: 12355371
21.  Pediatric HIV Type 1 Vaccine Trial Acceptability among Mothers in Kenya 
Vaccination of infants against human immunodeficiency virus type 1 (HIV-1) may prevent mother-to-child HIV-1 transmission. Successful trials and immunization efforts will depend on the willingness of individuals to participate in pediatric vaccine research and acceptance of infant HIV-1 vaccines. In a cross-sectional study, pregnant women presenting to a Nairobi antenatal clinic for routine care were interviewed regarding their attitudes toward participation in research studies and HIV-1 vaccine acceptability for their infants. Among 805 women, 782 (97%) reported they would vaccinate their infant against HIV-1 and 729 (91%) reported willingness to enroll their infant in a research study. However, only 644 (80%) would enroll their infants if HIV-1 testing was required every 3 months and 513 (64%) would agree to HIV-1 vaccine trial participation. Reasons for not wanting to enroll in a pediatric HIV-1 vaccine trial included concerns about side effects (75%), partner objection (34%), and fear of discrimination (10%), HIV-1 acquisition (8%), or false-positive HIV-1 results (5%). The strongest correlate of pediatric vaccine trial participation was maternal willingness to be a vaccine trial participant herself; in univariate and multivariate models this was associated with a 17-fold increased likelihood of participation (HR 17.1; 95% CI 11.7–25; p < 0.001). We conclude from these results that immunizing infants against HIV-1 and participation in pediatric vaccine trials are generally acceptable to women at high risk for HIV-1 infection. It will be important to address barriers identified in this study and to include male partners when mobilizing communities for pediatric HIV-1 vaccine trials and immunization programs.
doi:10.1089/aid.2006.22.491
PMCID: PMC3382079  PMID: 16796522
22.  Breast-Milk Infectivity in Human Immunodeficiency Virus Type 1–Infected Mothers 
The Journal of Infectious Diseases  2003;187(5):736-740.
Human immunodeficiency virus type 1 (HIV-1) is transmitted through blood, genital secretions, and breast milk. The probability of heterosexual transmission of HIV-1 per sex act is .0003–0015, but little is known regarding the risk of transmission per breast-milk exposure. We evaluated the probability of breast-milk transmission of HIV-1 per liter of breast milk ingested and per day of breast-feeding in a study of children born to HIV-1–infected mothers. The probability of breast-milk transmission of HIV-1 was .00064 per liter ingested and .00028 per day of breast-feeding. Breast-milk infectivity was significantly higher for mothers with more-advanced disease, as measured by prenatal HIV-1 RNA plasma levels and CD4 cell counts. The probability of HIV-1 infection per liter of breast milk ingested by an infant is similar in magnitude to the probability of heterosexual transmission of HIV-1 per unprotected sex act in adults.
doi:10.1086/374272
PMCID: PMC3382109  PMID: 12599046
23.  Breast Milk α-Defensins Are Associated with HIV Type 1 RNA and CC Chemokines in Breast Milk But Not Vertical HIV Type 1 Transmission 
α-Defensins are proteins exhibiting in vitro anti-HIV-1 activity that may protect against mother-to-child transmission of HIV-1 via breast milk. Correlates of α-defensins in breast milk and transmission risk were determined in a cohort of HIV-1-infected pregnant women in Nairobi followed for 12 months postpartum with their infants. Maternal blood was collected antenatally and at delivery for HIV-1 viral load and infant HIV-1 infection status was determined <48 h after birth and at months 1, 3, 6, 9, and 12. Breast milk specimens collected at month 1 were assayed for α-defensins, HIV-1 RNA, subclinical mastitis, and CC and CXC chemokines. We detected α-defensins in breast milk specimens from 108 (42%) of 260 HIV-1-infected women. Women with detectable α-defensins (≥50 pg/ml) had a median concentration of 320 pg/ml and significantly higher mean breast milk HIV-1 RNA levels than women with undetectable α-defensins (2.9 log10 copies/ml versus 2.5 log10 copies/ml, p = 0.003). Increased α-defensins concentrations in breast milk were also associated with subclinical mastitis (Na+/K+ ratio > 1) and increased breast milk chemokine levels. Overall, 40 (15%) infants were HIV-1 uninfected at birth and subsequently acquired HIV-1. There was no significant association between month 1 α-defensins and risk of HIV-1 transmission. In conclusion, α-defensins were associated with breast milk HIV-1 viral load, chemokine levels, and subclinical mastitis, all of which may alter risk of infant HIV-1 acquisition. Despite these associations there was no significant relationship between breast milk α-defensins and mother-to-child transmission, suggesting a complex interplay between breast milk HIV-1, inflammation, and antiinfective factors.
doi:10.1089/aid.2006.0125
PMCID: PMC3382116  PMID: 17331027
24.  Breast milk HIV-1 suppression and decreased transmission: a randomized trial comparing HIVNET 012 nevirapine versus short-course zidovudine 
AIDS (London, England)  2005;19(13):1415-1422.
Objective
To compare the effect of perinatal regimens of short-course nevirapine (HIVNET 012) and zidovudine [Thai-Centers for Disease Control and Prevention (CDC) regimen] on breast milk viral shedding and perinatal transmission during the first 6 weeks postpartum in a randomized clinical trial.
Design
Randomized clinical trial.
Methods
Pregnant HIV-1 seropositive women in Nairobi, Kenya who planned to breastfeed were randomized to HIVNET 012 or Thai-CDC regimens. Two to four breast milk samples were collected each week between delivery and 6 weeks postpartum. Breast milk HIV-1 RNA was quantified using the Gen-Probe TMA assay. Infants were tested for HIV-1 DNA at birth and 6 weeks.
Results
From March to October 2003, 76 women were enrolled and 795 breast milk samples were collected from 60 women who were randomized and followed after delivery. Between 3 and 21 days postpartum, nevirapine was associated with significantly greater suppression of breast milk log10 HIV-1 RNA: days 3 to 7 (1.98 versus 2.42, P = 0.1); days 8 to 14 (1.78 versus 2.48, P = 0.005); days 15 to 21 (1.90 versus 2.97, P = 0.003). At 6 weeks, the HIV-1 perinatal transmission rate was significantly lower among those who took nevirapine than zidovudine (6.8% versus 30.3%, P = 0.02).
Conclusions
Compared to a peripartum zidovudine regimen, nevirapine was significantly more likely to decrease HIV-1 RNA in breast milk during the first week and through the third week postpartum following single-dose administration, and corresponded with decreased transmission risk at 6 weeks. Sustained breast milk HIV-1 suppression may contribute to the ability of nevirapine to decrease perinatal transmission of HIV-1.
PMCID: PMC3381340  PMID: 16103773
Africa; vertical transmission; mother-to-child transmission; HIV-1; perinatal transmission; nevirapine; zidovudine
25.  Predictors of Early Mortality in a Cohort of Human Immunodeficiency Virus Type 1-Infected African Children 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
PMCID: PMC3380074  PMID: 15194835
Human immunodeficiency virus type 1; disease progression; mortality; predictors

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