Publications (7)138.69 Total impact
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Article: Impact of infection with human immunodeficiency virus-1 (HIV) on the risk of cancer among children in Malawi - preliminary findings
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ABSTRACT: Abstract Background The impact of infection with HIV on the risk of cancer in children is uncertain, particularly for those living in sub-Saharan Africa. In an ongoing study in a paediatric oncology centre in Malawi, children (aged ≤ 15 years) with known or suspected cancers are being recruited and tested for HIV and their mothers or carers interviewed. This study reports findings for children recruited between 2005 and 2008. Methods Only children with a cancer diagnosis were included. Odds ratios (OR) for being HIV positive were estimated for each cancer type (with adjustment for age (<5 years, ≥ 5 years) and sex) using children with other cancers and non-malignant conditions as a comparison group (excluding the known HIV-associated cancers, Kaposi sarcoma and lymphomas, as well as children with other haematological malignancies or with confirmed non-cancer diagnoses). Results Of the 586 children recruited, 541 (92%) met the inclusion criteria and 525 (97%) were tested for HIV. Overall HIV seroprevalence was 10%. Infection with HIV was associated with Kaposi sarcoma (29 cases; OR = 93.5, 95% CI 26.9 to 324.4) and with non-Burkitt, non-Hodgkin lymphoma (33 cases; OR = 4.4, 95% CI 1.1 to 17.9) but not with Burkitt lymphoma (269 cases; OR = 2.2, 95% CI 0.8 to 6.4). Conclusions In this study, only Kaposi sarcoma and non-Burkitt, non-Hodgkin lymphoma were associated with HIV infection. The endemic form of Burkitt lymphoma, which is relatively frequent in Malawi, was not significantly associated with HIV. While the relatively small numbers of children with other cancers, together with possible limitations of diagnostic testing may limit our conclusions, the findings may suggest differences in the pathogenesis of HIV-related malignancies in different parts of the world.Infectious Agents and Cancer. 01/2010; -
Article: Associations between Burkitt lymphoma among children in Malawi and infection with HIV, EBV and malaria: results from a case-control study.
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ABSTRACT: Burkitt lymphoma, a childhood cancer common in parts of sub-Saharan Africa, has been associated with Epstein Barr Virus (EBV) and malaria, but its association with human immunodeficiency virus (HIV) is not clear. We conducted a case-control study of Burkitt lymphoma among children (aged < or = 15 years) admitted to the pediatric oncology unit in Blantyre, Malawi between July 2005 and July 2006. Cases were 148 children diagnosed with Burkitt lymphoma and controls were 104 children admitted with non-malignant conditions or cancers other than hematological malignancies and Kaposi sarcoma. Interviews were conducted and serological samples tested for antibodies against HIV, EBV and malaria. Odds ratios for Burkitt lymphoma were estimated using unconditional logistic regression adjusting for sex, age, and residential district. Cases had a mean age of 7.1 years and 60% were male. Cases were more likely than controls to be HIV positive (Odds ratio (OR)) = 12.4, 95% Confidence Interval (CI) 1.3 to 116.2, p = 0.03). ORs for Burkitt lymphoma increased with increasing antibody titers against EBV (p = 0.001) and malaria (p = 0.01). Among HIV negative participants, cases were thirteen times more likely than controls to have raised levels of both EBV and malaria antibodies (OR = 13.2; 95% CI 3.8 to 46.6; p = 0.001). Reported use of mosquito nets was associated with a lower risk of Burkitt lymphoma (OR = 0.2, 95% CI, 0.03 to 0.9, p = 0.04). Our findings support prior evidence that EBV and malaria act jointly in the pathogenesis of Burkitt lymphoma, suggesting that malaria prevention may decrease the risk of Burkitt lymphoma. HIV may also play a role in the etiology of this childhood tumor.PLoS ONE 01/2008; 3(6):e2505. · 4.09 Impact Factor -
Article: Nevirapine and zidovudine at birth to reduce perinatal transmission of HIV in an African setting: a randomized controlled trial.
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ABSTRACT: Antenatal counseling and human immunodeficiency virus (HIV) testing are not universal in Africa; thus, women often present in labor with unknown HIV status without receiving the HIVNET 012 nevirapine (NVP) regimen (a single oral dose of NVP to the mother at the start of labor and to the infant within 72 hours of birth). To determine risk of mother-to-child transmission of HIV when either standard use of NVP alone or in combination with zidovudine (ZDV) was administered to infants of women tested at delivery. A randomized, open-label, phase 3 trial conducted between April 1, 2000, and March 15, 2003, at 6 clinics in Blantyre, Malawi, Africa. The trial included all infants born to 894 women who were HIV positive, received NVP intrapartum, and were previously antiretroviral treatment-naive. Infants were randomly assigned to NVP (n = 448) and NVP plus ZDV (n = 446). Infants were enrolled at birth, observed at 6 to 8 weeks, and followed up through 3 to 18 months. The HIV status of 90% of all infants was established at 6 to 8 weeks. Mothers received a 200-mg single oral dose of NVP intrapartum and infants received either 2-mg/kg oral dose of NVP or NVP (same dose) plus 4 mg/kg of ZDV twice per day for a week. HIV infection of infant at birth and 6 to 8 weeks, and adverse events. The mother-to-child transmission of HIV at birth was 8.1% (36/445) in infants administered NVP only and 10.1% (45/444) in those administered NVP plus ZDV (P =.30). A life table estimate of transmission at 6 to 8 weeks was 14.1% (95% confidence interval [CI], 10.7%-17.4%) in infants who received NVP and 16.3% (95% CI, 12.7%-19.8%) in those who received NVP plus ZDV (P =.36). For infants not infected at birth and retested at 6 to 8 weeks, transmission was 6.5% (23/353) in those who received NVP only and 6.9% (25/363) in those who received NVP plus ZDV (P =.88). Almost all infants (99%-100%) were breastfed at 1 week and 6 to 8 weeks. Grades 3 and 4 adverse events were comparable; 4.9% (22/448) and 5.4% (24/446) in infants receiving NVP only and NVP plus ZDV, respectively (P =.76). The frequency of mother-to-child HIV transmission at 6 to 8 weeks in our 2 study groups was comparable with that observed for other perinatal HIV intervention studies among breastfeeding women in Africa. The safety of the regimen containing neonatal ZDV was similar to that of a standard NVP regimen.JAMA The Journal of the American Medical Association 08/2004; 292(2):202-9. · 30.03 Impact Factor -
Article: Short postexposure prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1: NVAZ randomised clinical trial.
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ABSTRACT: In sub-Saharan Africa, most women present late for delivery with unknown HIV status, which limits the use of intrapartum nevirapine to prevent mother-to-child transmission of HIV. We aimed to determine whether post-exposure prophylaxis of nevirapine plus zidovudine given to babies only reduced transmission of HIV more than did a regimen of nevirapine alone. We randomly assigned 1119 babies of Malawian women with HIV-1 who presented late (ie, within 2 h of expected delivery) to either nevirapine alone or nevirapine and zidovudine. Both drugs were given immediately after birth: one dose of nevirapine (2 mg/kg weight) was given as a single dose; babies in the nevirapine plus zidovudine group also received zidovudine twice daily for 1 week (4 mg/kg weight). Infant HIV infection was determined at birth and at 6-8 weeks. Primary outcome was HIV infection in babies at 6-8 weeks in those not infected at birth. Analysis was by intention to treat. The overall rate of mother-to-child transmission at 6-8 weeks was 15.3% in 484 babies who received nevirapine and zidovudine and 20.9% in 468 babies who received nevirapine only (p=0.03). At 6-8 weeks, in babies who were HIV negative at birth, 34 (7.7%) babies who had nevirapine and zidovudine and 51 (12.1%) who received nevirapine only were infected (p=0.03)-a protective efficacy of 36%. This finding remained after controlling for maternal viral load and other factors at baseline. Adverse events were mild and of similar frequency in the two groups. Postexposure prophylaxis can offer protection against HIV infection to babies of women who missed opportunities to be counselled and tested before or during pregnancy. The nevirapine and zidovudine regimen is safe and easy to implement.The Lancet 10/2003; 362(9391):1171-7. · 38.28 Impact Factor -
Article: Effect of HIV-1 antiretroviral prophylaxis on hepatic and hematological parameters of African infants.
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ABSTRACT: To measure hepatic and hematological parameters among neonates randomized to receive ultra-short antiretroviral regimens. As part of an on-going clinical trial in Malawi, infants born to women who received (early presenters) or did not receive (late presenters) standard intrapartum nevirapine (NVP) dosing were randomized to receive orally either single dose NVP alone or NVP plus zidovudine (twice daily for 1 week). An additional group of untreated infants (born to HIV-uninfected women) was enrolled as a control. Laboratory measurements were performed at birth and repeated at 6 weeks of age. Serum alanine aminotransferase (ALT) was measured on approximately 200 infants consecutively enrolled and randomized at the start of the trial. Complete blood count (CBC) was performed on approximately 800 infants at birth and 600 infants at 6 weeks of age. ALT and CBC were also determined on approximately 200 control infants. At birth there were no differences in ALT values between the groups of children. At 6 weeks of age, ALT levels were significantly higher among the treated groups compared with control group (geometric mean of 11.5 U/l for controls and 16.2-19.1 U/l for treated groups; P < 0.0001). Hematological parameters did not differ between groups at birth. At 6 weeks of age, levels of hemoglobin, hematocrit, granulocytes, and platelets were significantly (P < 0.0001) lower among antiviral drug-treated groups compared with controls. These changes were consistent with grade 1 (mild) toxicity, and were more noticeable among HIV-infected infants. Hepatic and hematologic abnormalities associated with short-term neonatal antiretrovirals among African children are minimal.AIDS 05/2002; 16(6):851-8. · 6.24 Impact Factor -
Article: HIV Transmission Through BreastfeedingA Study in Malawi
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ABSTRACT: Context Understanding the risk of human immunodeficiency virus (HIV) transmission through breastfeeding is essential for advising HIV-infected mothers and formulating public health policy recommendations.Objective To measure the frequency, timing, and risk factors of HIV transmission through breast milk.Design Prospective cohort study conducted between 1994 and 1997, with follow-up of infants through 24 months of age.Setting Postnatal clinic of tertiary care hospital, Blantyre, Malawi.Participants A total of 672 infants (HIV-negative at birth) born to HIV-infected women who had not received antiretroviral drugs during or after pregnancy.Main Outcome Measure Incidence of HIV in breastfed infants by age and maternal and infant risk factors for HIV transmission, using proportional hazard models to derive risk ratios (RRs) and 95% confidence intervals (CIs).Results Forty-seven children became HIV-infected while breastfeeding but none after breastfeeding had stopped. The cumulative infection rate while breastfeeding, from month 1 to the end of months 5, 11, 17, and 23, was 3.5%, 7.0%, 8.9%, and 10.3%, respectively. Incidence per month was 0.7% during age 1 to 5 months, 0.6% during age 6 to 11 months, and 0.3% during age 12 to 17 months (P=.01 for trend). The only factors significantly associated with low risk of postnatal HIV transmission in a multivariate model were high maternal parity (RR, 0.23; 95% CI, 0.09-0.56) and older maternal age (RR, 0.44; 95% CI, 0.23-0.84).Conclusions Our data suggest that the risk of HIV infection is highest in the early months of breastfeeding, which should be considered in formulating breastfeeding policy recommendations. Figures in this Article Mother-to-child transmission of human immunodeficiency virus (HIV) can occur in utero, intrapartum, and postnatally.1- 2 Postnatal HIV transmission through HIV-contaminated breast milk is of particular concern in many developing countries, where HIV infection in women is common and breastfeeding is almost universally practiced. Transmission of HIV through breast milk has been documented in many studies,3- 12 and HIV has been found in breast milk samples of HIV-infected women.13- 16 Ascertaining the transmission risk of HIV at different times during the breastfeeding period has become particularly important, because it has recently been shown that in utero and intrapartum transmission can be decreased by approximately 50% when short-course, oral antiretroviral therapy is used during pregnancy through labor.17 In breastfeeding populations, however, any decrease in in utero and intrapartum transmission of HIV achieved through such regimens or other methods of prevention will result in a larger number of infants, who, though uninfected at birth, become exposed to HIV through breast milk. In this study, we investigated the risk of HIV transmission through breastfeeding in an urban setting in Malawi, where HIV prevalence in nursing women is approximately 30%, and breastfeeding is the recommended method of infant feeding. A revised statement in 1998 by the Joint United Nations Programme on HIV/AIDS18 recommended that women be offered HIV counseling and testing, that they be informed of risks and benefits of breastfeeding if the mother is HIV-infected, and that they make a decision that takes into account their individual and family situations. A better understanding of the level of risk and the timing of infant HIV infection throughout the breastfeeding period will help to inform women about transmission risks and to assess policy options about breastfeeding by HIV-infected women.JAMA The Journal of the American Medical Association 282(8):744-749. · 30.03 Impact Factor -
Article: Nevirapine and Zidovudine at Birth to Reduce Perinatal Transmission of HIV in an African SettingA Randomized Controlled Trial
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ABSTRACT: Context Antenatal counseling and human immunodeficiency virus (HIV) testing are not universal in Africa; thus, women often present in labor with unknown HIV status without receiving the HIVNET 012 nevirapine (NVP) regimen (a single oral dose of NVP to the mother at the start of labor and to the infant within 72 hours of birth).Objective To determine risk of mother-to-child transmission of HIV when either standard use of NVP alone or in combination with zidovudine (ZDV) was administered to infants of women tested at delivery.Design, Setting, and Participants A randomized, open-label, phase 3 trial conducted between April 1, 2000, and March 15, 2003, at 6 clinics in Blantyre, Malawi, Africa. The trial included all infants born to 894 women who were HIV positive, received NVP intrapartum, and were previously antiretroviral treatment–naive. Infants were randomly assigned to NVP (n = 448) and NVP plus ZDV (n = 446). Infants were enrolled at birth, observed at 6 to 8 weeks, and followed up through 3 to 18 months. The HIV status of 90% of all infants was established at 6 to 8 weeks.Intervention Mothers received a 200-mg single oral dose of NVP intrapartum and infants received either 2-mg/kg oral dose of NVP or NVP (same dose) plus 4 mg/kg of ZDV twice per day for a week.Main Outcome Measures HIV infection of infant at birth and 6 to 8 weeks, and adverse events.Results The mother-to-child transmission of HIV at birth was 8.1% (36/445) in infants administered NVP only and 10.1% (45/444) in those administered NVP plus ZDV (P = .30). A life table estimate of transmission at 6 to 8 weeks was 14.1% (95% confidence interval [CI], 10.7%-17.4%) in infants who received NVP and 16.3% (95% CI, 12.7%-19.8%) in those who received NVP plus ZDV (P = .36). For infants not infected at birth and retested at 6 to 8 weeks, transmission was 6.5% (23/353) in those who received NVP only and 6.9% (25/363) in those who received NVP plus ZDV (P = .88). Almost all infants (99%-100%) were breastfed at 1 week and 6 to 8 weeks. Grades 3 and 4 adverse events were comparable; 4.9% (22/448) and 5.4% (24/446) in infants receiving NVP only and NVP plus ZDV, respectively (P = .76).Conclusions The frequency of mother-to-child HIV transmission at 6 to 8 weeks in our 2 study groups was comparable with that observed for other perinatal HIV intervention studies among breastfeeding women in Africa. The safety of the regimen containing neonatal ZDV was similar to that of a standard NVP regimen. Figures in this Article Mother-to-child transmission of human immunodeficiency virus (HIV) in sub-Saharan Africa can be decreased with use of nevirapine (NVP) and zidovudine (ZDV).1- 3 Phase 1 and 3 studies have evaluated the pharmacokinetics, safety, and efficacy of NVP among women and infants who received various ZDV regimens.4- 6 Information on the efficacy of adding neonatal ZDV to a standard regimen of NVP (the HIVNET 012 regimen of an intrapartum single 200-mg oral dose plus a single infant oral dose of 2 mg/kg1) is limited. This information is needed because most women in sub-Saharan Africa do not receive antenatal antiretroviral treatment of ZDV or other regimens and present in labor with HIV status unknown. We hypothesized that in situations in which the mother is tested for HIV at the time of presentation for delivery, giving 2 short drug regimens to the infant at birth would be more effective in increasing viral suppression and thus reducing mother-to-child transmission of HIV than a single regimen.7 Additionally, a dual regimen could limit development of antiviral resistance to NVP because this has been reported to occur rapidly and frequently in more than 40% of infants who received a single NVP dose.8- 9 With extensive evidence that substantial transmission occurs very late during gestation,10 it is difficult to assume that the impact of postexposure prophylaxis with ZDV, especially when combined with NVP (which has a long-acting effect),4,11- 12 will be limited only to uninfected infants at birth. We recently reported that postexposure prophylaxis with NVP plus ZDV only to the infant, without the mother receiving intrapartum NVP, significantly reduced mother-to-child transmission of HIV by approximately 36% in Malawi, Africa.13 In the current study, our goal was to assess mother-to-child transmission when both mother and infant had received a standard NVP regimen compared with mother-to-child transmission when both mother and infant had received the same standard NVP regimen with the addition of the infant receiving ZDV for a week.JAMA The Journal of the American Medical Association 292(2):202-209. · 30.03 Impact Factor
