Showing papers by "Irving F. Hoffman published in 2010"
TL;DR: The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding.
Abstract: Among mother–infant pairs, 5.0% of infants were HIV-1–positive at 2 weeks of life. The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group (5.7%) than in either the maternal-regimen group (2.9%, P = 0.009) or the infant-regimen group (1.7%, P<0.001). The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0% in the control group, 4.1% in the maternal-regimen group (P = 0.02), and 2.6% in the infant-regimen group (P<0.001). The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen (6.2%) than among those in either the nevirapine group (2.6%) or the control group (2.3%). Among infants receiving nevirapine, 1.9% had a hypersensitivity reaction. Conclusions The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding. (ClinicalTrials .gov number, NCT00164736.)
424 citations
TL;DR: Different relationships between virus in blood and semen that can significantly alter the composition of the viral population at the source that is most proximal to the transmitted virus are defined.
Abstract: HIV-1 is present in anatomical compartments and bodily fluids. Most transmissions occur through sexual acts, making virus in semen the proximal source in male donors. We find three distinct relationships in comparing viral RNA populations between blood and semen in men with chronic HIV-1 infection, and we propose that the viral populations in semen arise by multiple mechanisms including: direct import of virus, oligoclonal amplification within the seminal tract, or compartmentalization. In addition, we find significant enrichment of six out of nineteen cytokines and chemokines in semen of both HIV-infected and uninfected men, and another seven further enriched in infected individuals. The enrichment of cytokines involved in innate immunity in the seminal tract, complemented with chemokines in infected men, creates an environment conducive to T cell activation and viral replication. These studies define different relationships between virus in blood and semen that can significantly alter the composition of the viral population at the source that is most proximal to the transmitted virus.
136 citations
TL;DR: The most recent study continues the trend of high susceptibility of gonococcal isolates to gentamicin in Malawi after 14 years of use and suggests agar dilution MICs may be substituted with the simpler E-test methods in future susceptibility testing.
Abstract: Background:Malawi adopted syndromic management of sexually transmitted infections in 1993. Based on clinical efficacy and cost, gentamicin 240 mg intramuscularly, and doxycycline 100 mg twice daily × 7 days was selected as the first line regimen to treat urethritis. We sought to establish current la
111 citations
TL;DR: The results indicate that a single variant was transmitted in a majority of cases (9 of 13 participants), which is analogous to what is observed in sexual transmission and most consistent with a genetic bottleneck during transmission by injection drug use that is due to a small inoculum, which most often results in the transmission of a low-complexity viral population.
Abstract: There are limited data on the genetic complexity of human immunodeficiency virus type 1 (HIV-1) after transmission among a cohort of injection drug users (IDUs). We used single-genome amplification of HIV-1 env to determine the genotypic characteristics of virus among IDUs with acute infection in St Petersburg, Russia. Our results indicate that a single variant was transmitted in a majority of cases (9 of 13 participants), which is analogous to what is observed in sexual transmission. These data are most consistent with a genetic bottleneck during transmission by injection drug use that is due to a small inoculum, which most often results in the transmission of a low-complexity viral population.
53 citations
TL;DR: Dyad interventions may not be sufficient to reduce injecting risk in IDU partnerships, but a combination of dyad and network interventions that target bothIDU partnerships and the entire IDU population may be more appropriate to address injecting risk among IDUs.
Abstract: In this study, we investigated how individual attributes, dyad characteristics and social network characteristics may influence engaging in receptive syringe sharing, distributive syringe sharing and sharing cookers in injecting partnerships of IDUs in St Petersburg, Russia. We found that all three levels were associated with injecting equipment sharing, and that dyad characteristics were modified by characteristics of the social network. Self-reported HIV discordance and male gender concordance played a role in the risk of equipment sharing. Dyad interventions may not be sufficient to reduce injecting risk in IDU partnerships, but a combination of dyad and network interventions that target both IDU partnerships and the entire IDU population may be more appropriate to address injecting risk among IDUs.
48 citations
TL;DR: An approach to injury surveillance is described, the utility of trauma scoring systems are examined, and steps necessary before such scoring systems can be reliably instituted in a resource-constrained setting are outlined.
Abstract: Injury is a major cause of morbidity and mortality in developing countries. Utilizing a partnership between Kamuzu Central Hospital (KCH) and the University of North Carolina Departments of Surgery, we describe an approach to injury surveillance, examine the utility of trauma scoring systems, and outline steps necessary before such scoring systems can be reliably instituted in a resource-constrained setting.
29 citations
TL;DR: In pregnant women in sub-Saharan Africa, most of whom were HIV-infected, neither trichomoniasis nor its treatment appears to influence the risk of preterm birth or a low-birth-weight infant.
Abstract: To determine whether treatment of trichomoniasis increases the risk of prematurity. Sub-analysis of a randomised trial. We analysed data from HPTN trial of antenatal and intrapartum antibiotics to reduce chorioamnionitis-related perinatal HIV transmission. Pregnant women from four sites in Africa. Gestational age at the time of delivery or mean birth weight. Of 2,428 women-infant pairs included, 428 (18%) had trichomoniasis at enrolment. There were no differences in infant age or birth weight between women with or without trichomoniasis. By randomisation group, there were no differences in gestational age at birth or birth weight. Of the 428 women diagnosed with trichomoniasis, 365 (83%) received antibiotics and 63 (15%) did not. In analysis of actual use of antibiotics, women with trichomoniasis who received no treatment were more likely to deliver a preterm infant when the symphysis-fundal height was used to estimate gestational age (36% v. 23%; p=0.03), but not when the Ballard score was used (16% v. 21%; p=0.41). There were no differences in mean birth weight between groups. In pregnant women in sub-Saharan Africa, most of whom were HIV-infected, neither trichomoniasis nor its treatment appears to influence the risk of preterm birth or a low-birth-weight infant.
28 citations
TL;DR: Cyclophosphamide may induce the lytic phase of EBV infection and is fairly effective in diminishing EBER-expressing tumor cells within 5 days, providing the rationale for a trial testing synergistic tumor cell killing using cycloph phosphamide with a drug like ganciclovir targeting lytically infected cells.
Abstract: Purpose: Some EBV-directed therapies are predicted to be effective only when lytic viral replication occurs. We studied whether cyclophosphamide chemotherapy induces EBV to switch from latent to lytic phases of infection in a series of EBV-associated Burkitt lymphomas. Experimental Design: Children with first presentation of an expanding, solid maxillary or mandibular mass consistent with Burkitt lymphoma underwent fine-needle aspiration just prior to the initiation of cyclophosphamide therapy and again 1 to 5 days later. Aspirated cells were examined for latent and lytic EBV infection using in situ hybridization to EBV-encoded RNA ( EBER ), immunohistochemical analysis of the lytic EBV proteins BZLF1 and BMRF1, reverse transcription PCR targeting BZLF1 transcripts, and EBV viral load measurement by quantitative PCR. Results: Among 21 lymphomas expressing EBER prior to chemotherapy, 9 of 10 still expressed EBER on day 1 after therapy whereas only 2 of 11 (18%) specimens still expressed EBER at days 3 to 5, implying that chemotherapy was fairly effective at eliminating latently infected cells. Neither of the lytic products, BZLF1 or BMRF1, were significantly upregulated at the posttherapy time points examined. However, EBV genomic copy number increased in 5 of 10 samples 1 day after treatment began, suggesting that viral replication occurs within the first 24 hours. Conclusion: Cyclophosphamide may induce the lytic phase of EBV infection and is fairly effective in diminishing EBER -expressing tumor cells within 5 days. These findings provide the rationale for a trial testing synergistic tumor cell killing using cyclophosphamide with a drug like ganciclovir targeting lytically infected cells. Clin Cancer Res; 16(7); 2055–64. ©2010 AACR.
20 citations
TL;DR: Episodic HSV treatment with aciclovir added to syndromic management of genital ulcer disease did not produce a significant clinical benefit in this African population.
Abstract: Objective By a randomised, double-blind, placebocontrolled trial of aciclovir 800 mg twice daily for 5 days added to the syndromic management of genital ulcer disease (GUD) to determine the impact on ulcer healing and HIV outcomes. Methods Patients presenting with GUD in Malawi were evaluated for HIV and herpes simplex virus type-2 (HSV-2) serologies, ulcer aetiology, lesional, genital and plasma HIV-1 RNA and CD4+ count. Patients were followed up at days 2, 4, 7, 14 and 28. The primary study outcome was ulcer healing at day 14, with secondary outcomes being lesional and genital HIV-1 shedding at day 14 and HIV-1 plasma viral load at day 28 among HIV-1/HSV-2 co-infected individuals. Results Four hundred and twenty-two patients (74% male) were randomised (208 to aciclovir, 214 to placebo), of whom 61% were HIV-1 seropositive and 72% HSV-2 seropositive; 67% (267/398) had HSV-2 ulcers. 85% of ulcers were healed at day 14 with no difference between treatment arms (risk ratio (RR)¼ 1.02, 95% CI 0.93 to 1.11). Among 244 HIV-1/HSV-2 coinfected individuals, aciclovir reduced lesional HIV-1 RNA (adjusted RR¼0.64, 95% CI 0.41 to 0.99) and seminal HIV-1 RNA (adjusted RR¼0.59, 95% CI 0.40 to 0.88), but not cervical HIV-1 RNA or plasma HIV-1 RNA. Conclusions Episodic HSV treatment with aciclovir added to syndromic management did not produce a significant clinical benefit in this African population.
20 citations
TL;DR: The authors' PAF analysis illustrates the public health impact of the substantial proportion of LPTs accounted for by high-risk women with both low CD4+ counts and high VLs, and additional strategies to reduce LPT for those not meeting criteria for antiretroviral therapy should be implemented.
Abstract: OBJECTIVES: Assess population attributable fractions (PAFs) for late postnatal transmission (LPT) of HIV-1 in a cohort of HIV-1-exposed infants. METHODS: We used data established from a risk factor analysis of LPT (negative HIV-1 results through the 4-6 week visit but positive assays thereafter through the 12-month visit) from a perinatal clinical trial conducted in 3 sub-Saharan countries. PAFs were calculated as the proportions of excess LPTs attributed to identified risk factors. RESULTS: For the cohort of 1317 infants 206 (15.6%) had only low maternal CD4 counts ( 50000 copies/mL) and 81 (6.2%) had both low CD4 counts and high VLs. Their PAFs were 26.0% [95% confidence interval (CI): 12.0% to 36.0%] 37.0% (95% CI: 22.0% to 51.0%) and 16.0% (95% CI: 6.0% to 25.0%) respectively. CONCLUSIONS: Our PAF analysis illustrates the public health impact of the substantial proportion of LPTs accounted for by high-risk women with both low CD4 counts and high VLs. In light of these results access to and use of antiretroviral therapy by high-risk HIV-1-infected pregnant women is essential. Additional strategies to reduce LPT for those not meeting criteria for antiretroviral therapy should be implemented.
19 citations
TL;DR: A pilot prevention of mother‐to‐child transmission post‐natal programme in Lilongwe, Malawi is evaluated through observed retention and infant diarrhoeal rates.
Abstract: Summary objective To evaluate a pilot prevention of mother-to-child transmission post-natal programme in Lilongwe, Malawi, through observed retention and infant diarrhoeal rates. methods Free fortified porridge and water hygiene packages were offered to mothers to encourage frequent post-natal visits and to reduce diarrhoeal rates in infants on replacement feeding. Participant retention and infant health outcome were assessed. results Of 474 patients enrolled, 357 (75.3%) completed 3-month follow-up visits. Ninety-nine percent of women reported hygiene package use, and only 17.7% (95% CI 13.8‐22.0%) of the infants had diarrhoea at least once over the 3-month period. Being 12 months or younger, confirmed HIV positive, access to tap water, and having a mother with diarrhoea were all associated with increased risk of infant diarrhoea. conclusion The majority of participants adhered to their scheduled visits and retention was favourable, possibly because of the introduction of hygiene and nutrition incentives. The infant diarrhoeal rate was low, suggesting benefits of regular medical care with hygiene package usage and reliable replacement feeding options. Continuation and expansion of the programme would allow further studies and improve the post-natal care of HIV-exposed infants in Malawi and in other resource-constrained countries.