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Biomedical subjects

James A McIntyre

Publications and source records attributed to James A McIntyre.

10 recordsLinked to original sources

Selection and persistence of viral resistance in HIV-infected children after exposure to single-dose nevirapine.

BACKGROUND: Single-dose nevirapine (sd-NVP) is the mainstay of prevention of mother-to-child transmission programs in developing countries. Exposure to sd-NVP selects for resistance mutations, however. We longitudinally assessed these mutations in HIV-1-infected infants from Soweto and Durban, South Africa. METHODS: We prospectively followed 465 infants who received sd-NVP after enrolling their mothers when pregnant. If HIV infected, their virus was genotyped, using the ViroSeq HIV-1 Genotyping System, to detect resistant mutations. Those with resistance were genotyped at 6 months and then every 6 months out to 18 months if resistance was detected at the previous visit. RESULTS: Of 53 HIV-infected infants, 24 (45.3%) had detectable resistance at their first visit, when the most frequent mutations were Y181C (75%), K103N (25%), and Y188C (12%). Of those whose visit was before 12 weeks of age, 2 of 42 infants shared identical resistance mutations with their mothers. By 18 months of age, 11 of 24 infants with resistance had died and 1 still had the Y181C mutation. CONCLUSIONS: Resistant mutations were selected in half of the infants exposed to sd-NVP, but fewer were detected over time and, unlike the case in their mothers, Y181C dominated initially and persists. Transient resistance mutations may have a negative impact on highly active antiretroviral therapy in infants and children.

Adult↗

Linking the global positioning system (GPS) to a personal digital assistant (PDA) to support tuberculosis control in South Africa: a pilot study.

BACKGROUND: Tuberculosis (TB) is the leading clinical manifestation of HIV infection and caseloads continue to increase in high HIV prevalence settings. TB treatment is prolonged and treatment interruption has serious individual and public health consequences. We assessed the feasibility of using a handheld computing device programmed with customised software and linked to a GPS receiver, to assist TB control programmes to trace patients who interrupt treatment in areas without useful street maps. In this proof of concept study, we compared the time taken to re-find a home comparing given residential addresses with a customised personalised digital assistant linked to a global positioning system (PDA/GPS) device. Additionally, we assessed the feasibility of using aerial photographs to locate homes. RESULTS: The study took place in two communities in Greater Johannesburg, South Africa: Wheillers Farm, a relatively sparsely populated informal settlement, and a portion of Alexandra, an urban township with densely populated informal settlements. Ten participants in each community were asked to locate their homes on aerial photographs. Nine from Wheillers Farm and six from Alexandra were able to identify their homes. The total time taken by a research assistant, unfamiliar with the area, to locate 10 homes in each community using the given addresses was compared with the total time taken by a community volunteer with half an hour of training to locate the same homes using the device. Time taken to locate the ten households was reduced by 20% and 50% in each community respectively using the PDA/GPS device. CONCLUSION: In this pilot study we show that it is feasible to use a simple PDA/GPS device to locate the homes of patients. We found that in densely populated informal settlements, GPS technology is more accurate than aerial photos in identifying homes and more efficient than addresses provided by participants. Research assessing issues of, confidentiality and cost effectiveness would have to be undertaken before implementing PDA/GPS - based technology for this application. However, this PDA/GPS device could be used to reduce part of the burden on TB control programs.

Anti-Retroviral Agents↗

High rates of HIV in surgical patients in Soweto, South Africa: impact on resource utilisation and recommendations for HIV testing.

Interactions between HIV and surgical diseases are relatively poorly described in high HIV prevalence settings. We report HIV prevalence and its associations in a prospective study of adults admitted to surgical units in Soweto, South Africa. Voluntary counselling and testing (VCT) for HIV was offered to surgical inpatients. Research nurses interviewed participants at enrolment and doctors reviewed records after discharge. In HIV-infected participants, CD4 counts and viral loads were ascertained. Of 1000 participants, 537 consented to VCT, of whom 176 (32.8%, 95% CI 28.8-36.9%) tested HIV positive. A history of tuberculosis (adjusted odds ratio (AOR) 3.0, 95% CI 1.5-6.2) or sexually transmitted infection (AOR 2.7, 95% CI 1.8-4.2) was associated with HIV infection. Diagnoses of cutaneous abscesses (OR 3.4, 95% CI 1.4-8.1) and anorectal sepsis (OR 3.1, 95% CI 1.1-9.0) were associated with HIV and indicated advanced disease. There were no differences in rates of operative procedures, wound sepsis, investigations or length of stay by HIV status. Hospital-acquired pneumonia was more common in HIV-infected participants (P=0.028). In conclusion, in this high HIV prevalence setting, resource utilisation is similar between HIV-infected and uninfected patients in surgical wards where high rates of HIV in young adults support routine HIV testing. WHO clinical staging of HIV should include anal sepsis as an indicator of advanced HIV disease.

Adult↗

Combining PMTCT with active case finding for tuberculosis.

Tuberculosis (TB) is the preeminent manifestation of HIV infection and has become a leading cause of maternal mortality and morbidity in high HIV-prevalence settings. Active TB in pregnant women has potentially serious consequences for fetuses and newborns. In Soweto, South Africa, there is a more than 90% uptake of voluntary counseling and HIV testing during routine antenatal care, and almost one third of pregnant women are HIV-infected. The posttest counseling session of the prevention of mother-to-child transmission program provides an opportunity to screen HIV-infected pregnant women for TB. In this study, 370 HIV-infected pregnant women were screened for symptoms of active TB by lay counselors at the posttest counseling session. If symptomatic, they were referred to nurses who investigated them further. Eight women were found to have previously undiagnosed, smear-negative, culture-confirmed TB (2160/100,000). The mean CD4 count in those with active TB compared to those without TB was 276 x 10(6) cells per liter vs 447 x 10(6) cells per liter (P = 0.051). Symptoms most associated with active TB were hemoptysis and fever. We conclude that rates of TB in HIV-infected pregnant women are high, and screening for TB during routine antenatal care should be implemented in high HIV-prevalence settings.

Adult↗

Controversies in the use of nevirapine for prevention of mother-to-child transmission of HIV.

The use of nevirapine to prevent mother-to-child transmission of HIV has been controversial. Claims of high rates of toxicity have not been confirmed in clinical trials or extensive programme experience of use of the regimen. Whilst single-dose nevirapine can reduce transmission rates to approximately 10-15%, this can be halved by the addition of single-dose nevirapine to short-course regimens of zidovudine. The selection of resistant virus is reported in 20-50% of mothers and 50% of infants following one dose of nevirapine, although the impact of this on future treatment options is not fully understood. An increased risk of severe hepatotoxicity has been reported with long-term nevirapine-containing triple-therapy treatment regimens in women with CD4+ counts > 250 cells/mm3.

Antiretroviral Therapy, Highly Active↗

Effect of HIV on women.

HIV infection impacts the lives of young girls and women globally, with both populations being socially and biologically susceptible to HIV acquisition. The predominant mode of transmission in most parts of the world is heterosexual contact; however, injection drug use is an important transmission mode in Central and Eastern Europe as well as in North America. In HIV-infected women, cervical disorders (including those related to human papillomavirus infection and cervical intraepithelial neoplasia), Candida vaginitis, and pelvic inflammatory disease may be more frequent and severe. Fertility is negatively affected by HIV infection, and HIV infection increases adverse pregnancy outcomes in resource-poor settings. In addition, women are more likely to have antiretroviral treatment side effects, and certain antiretroviral regimens may impair contraceptive efficacy. Prevention strategies are presently not female-controlled.

Adolescent↗

A randomized trial of two postexposure prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of untreated mothers.

BACKGROUND: Single-dose nevirapine (NVP) prophylaxis to mother and infant is widely used in resource-constrained settings for preventing mother-to-child transmission (MTCT) of HIV-1. Where women do not access antenatal care or HIV testing, postexposure prophylaxis to the infant may be an important preventative strategy. METHODS: This multicentre, randomized, open-label clinical trial (October 2000 to September 2002) in South Africa compared single-dose NVP with 6 weeks of zidovudine (ZDV), commenced within 24 h of delivery among 1051 infants whose mothers had no prior antiretroviral therapy. HIV-1 infection rates were ascertained at birth, and at 6 and 12 weeks of age. Kaplan-Meier survival methods were used to estimate HIV-1 infection rates in an intention-to-treat analysis. RESULTS: Overall, 6 week and 12 week MTCT probability was 12.8% [95% confidence interval (CI),10.5-15.0] and 16.3% (95% CI,13.4-19.2), respectively. At 12 weeks, among infants who were not infected at birth, 24 (7.9%) infections occurred in the NVP arm and 41 (13.1%) in the ZDV arm (log rank P = 0.06). Using multivariate analysis, factors associated with infection following birth were ZDV use [odds ratio (OR), 1.8; 95% CI,1.1-3.2; P = 0.032), maternal CD4 cell count < 500 x 10(6) cells/l (OR, 2.5; 95% CI,1.3-5.0; P = 0.007), maternal viral load > 50 000 copies/ml (OR, 3.6; 95% CI,2.0-6.2; P < 0.0001) and breastfeeding (OR, 2.2; 95% CI,1.3-3.8; P = 0.006). CONCLUSION: A single-dose of NVP given to infants offers protection against HIV-1 infection and should be a strategy used in infants of mothers with untreated HIV infection.

Anti-HIV Agents↗

Prevalence and patterns of gender-based violence and revictimization among women attending antenatal clinics in Soweto, South Africa.

Gender-based violence is a key health risk for women globally and in South Africa. The authors analyzed data from 1,395 interviews with women attending antenatal clinics in Soweto, South Africa, between November 2001 and April 2002 to estimate the prevalence of physical/sexual partner violence (55.5%), adult sexual assault by nonpartners (7.9%), child sexual assault (8.0%), and forced first intercourse (7.3%). Age at first experience of each type of violence was modeled by the Kaplan-Meier method, and Cox hazard models with time-varying covariates were used to explore whether child sexual assault and forced first intercourse were associated with risk of violent revictimization in adulthood. Child sexual assault was associated with increased risk of physical and/or sexual partner violence (risk ratio = 2.43, 95% confidence interval: 1.93, 3.06) and with adult sexual assault by a nonpartner (risk ratio = 2.33, 95% confidence interval: 1.40, 3.89). Forced first intercourse was associated with increased risk of physical and/or sexual partner violence (risk ratio = 2.64, 95% confidence interval: 2.07, 3.38) and nonsignificantly with adult sexual assault by a nonpartner (risk ratio = 2.14, 95% confidence interval: 0.92, 4.98). This study confirms the need for increased attention by the public health community to primary and secondary prevention of gender-based violence, with a specific need to reduce risk among South African adolescents.

Adolescent↗