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Biomedical subjects

Glenda E Gray

Publications and source records attributed to Glenda E Gray.

17 recordsLinked to original sources
PubMed2006

In vivo effects of HIV-1 exposure in the presence and absence of single-dose nevirapine on cellular plasma activation markers of infants born to HIV-1-seropositive mothers.

Short-course antiretroviral drug regimens reduce the risk of mother-to-child transmission of HIV-1, but mechanisms affording protection of such interventions remain poorly defined. Because T-cell activation is an important factor in productive HIV-1 infection, we tested the hypothesis that single-dose nevirapine (NVP) reduces immune activation, which in turn reduces the likelihood of transmission. We compared concentrations of cord and maternal blood plasma immune activation markers, neopterin, beta2-microglobulin, and soluble l-selectin, in 2 groups of HIV-1-exposed newborns whose mothers either received NVP at the onset of labor or who only received NVP as postexposure prophylaxis within 72 hours of birth and among HIV-unexposed controls. In utero exposure of the infant to HIV-1, regardless of NVP exposure, led to demonstrable increases in immune activation markers, this being most notable in the presence of preexisting infection. Contrary to what was hypothesized, immune activation was increased by prebirth exposure to single-dose NVP, with this effect being enhanced in infants already infected at birth. Our data suggest that reductions in immune activation do not explain transmission prevention effects of single-dose NVP. Our data also suggest a biological explanation for why HIV-1-infected infants exposed perinatally to antiretroviral drugs might experience hastened disease progression, namely, in some HIV-1-infected individuals, NVP may synergize with HIV-1 to enhance an environment that favors increased HIV-1 replication.

Adult↗
PubMed2006

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↗
PubMed2006

Efavirenz use during pregnancy and for women of child-bearing potential.

BACKGROUND: Efavirenz is the preferred non-nucleoside reverse transcriptase inhibitor for first-line antiretroviral treatment in many countries. For women of childbearing potential, advantages of efavirenz are balanced by concerns that it is teratogenic. This paper reviews evidence of efavirenz teratogenicity and considers implications in common clinical scenarios. FINDINGS: Concerns of efavirenz-induced fetal effects stem from animal studies, although the predictive value of animal data for humans is unknown. Four retrospective cases of central nervous system birth defects in infants with first trimester exposure to efavirenz have been interpreted as being consistent with animal data. In a prospective pregnancy registry, which is subject to fewer potential biases, no increase was detected in overall risk of birth defects following exposure to efavirenz in the first-trimester. DISCUSSION: For women planning a pregnancy or not using contraception, efavirenz should be avoided if alternatives are available. According to WHO guidelines for resource-constrained settings, benefits of efavirenz are likely to outweigh risks for women using contraception. Women who become pregnant while receiving efavirenz often consider drug substitution or temporarily suspending treatment. Both options have substantial risks for maternal and fetal health which, we argue, appear unjustified after the critical period of organogenesis (3-8 weeks post-conception). Efavirenz-based triple regimens, initiated after the first trimester of pregnancy and discontinued after childbirth, are potentially an important alternative for reducing mother-to-child transmission in pregnant women who do not yet require antiretroviral treatment. CONCLUSION: Current recommendations for care for women who become pregnant while receiving efavirenz may need to be re-considered, particularly in settings with limited alternative drugs and laboratory monitoring. With current data limitations, additional adequately powered prospective studies are needed.

Journal Article↗
PubMed2006

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↗
PubMed2006

Reduced ability of newborns to produce CCL3 is associated with increased susceptibility to perinatal human immunodeficiency virus 1 transmission.

The role of CC chemokines in protection against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission is not well understood. It was observed that mitogen-induced production of CCL3 and CCL4 by cord-blood mononuclear cells was increased among infants born to HIV-positive compared with HIV-negative mothers, and that a deficiency in production of CCL3 was associated with increased susceptibility to intrapartum HIV-1 infection. CCL3-L1 gene copy number was associated with CCL3 production and with vertical transmission. However, at equivalent CCL3-L1 gene copy numbers, infants who acquired HIV-1 infection relative to their exposed but uninfected counterparts had lower production of CCL3, suggesting that they may harbour some non-functional copies of this gene. Nucleotide changes that may influence CCL3 production were evident in the CCL3 and CCL3-L1 genes upstream of exon 2. Our findings suggest that infants who display a deficient-production phenotype of CCL3 are at increased risk of acquiring HIV-1, indicating that this chemokine in particular plays an essential role in protective immunity.

Base Sequence↗
PubMed2006

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↗
PubMed2005

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↗
PubMed2005

Progress and Emerging Challenges in Preventing Mother-to-Child Transmission.

There is a widening gulf between the effectiveness of interventions for preventing mother-to-child transmission (PMTCT) of HIV in sub-Saharan Africa and other regions of the world. Compared with long-course, triple antiretroviral regimens used in Brazil, Europe, and the United States, most countries in sub-Saharan Africa use a less effective regimen consisting of single-dose nevirapine (NVP). Furthermore, the documentation of unacceptable levels of resistance following this regimen makes it prudent to review current PMTCT strategies. Not only is it necessary to review the use of single-dose NVP for PMTCT, but efforts to minimize breast milk transmission of HIV should be enhanced. This review summarizes the programmatic and evidence-based reasons for adopting a standardized approach to long-course, triple-drug MTCT prophylaxis in sub-Saharan Africa. Antiretroviral treatment programs in resource-constrained settings have achieved similar levels of effectiveness as high-income countries, despite adopting standardized approaches to antiretroviral treatment. Similarly, in resource-constrained settings with adequate infrastructure and programmatic capacity, use of standardized, long-course, triple-drug regimens for MTCT prevention are likely to achieve levels of effectiveness seen in Brazil, Europe, and the United States.

Journal Article↗
PubMed2004

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↗
PubMed2004

Gender-based violence, relationship power, and risk of HIV infection in women attending antenatal clinics in South Africa.

BACKGROUND: Gender-based violence and gender inequality are increasingly cited as important determinants of women's HIV risk; yet empirical research on possible connections remains limited. No study on women has yet assessed gender-based violence as a risk factor for HIV after adjustment for women's own high-risk behaviours, although these are known to be associated with experience of violence. METHODS: We did a cross-sectional study of 1366 women presenting for antenatal care at four health centres in Soweto, South Africa, who accepted routine antenatal HIV testing. Private face-to-face interviews were done in local languages and included assessement of sociodemographic characteristics, experience of gender-based violence, the South African adaptation of the Sexual Relationship Power Scale (SRPS), and risk behaviours including multiple, concurrent, and casual male partners, and transactional sex. FINDINGS: After adjustment for age and current relationship status and women's risk behaviour, intimate partner violence (odds ratio 1.48, 95% CI 1.15-1.89) and high levels of male control in a woman's current relationship as measured by the SRPS (1.52, 1.13-2.04) were associated with HIV seropositivity. Child sexual assault, forced first intercourse, and adult sexual assault by non-partners were not associated with HIV serostatus. INTERPRETATION: Women with violent or controlling male partners are at increased risk of HIV infection. We postulate that abusive men are more likely to have HIV and impose risky sexual practices on partners. Research on connections between social constructions of masculinity, intimate partner violence, male dominance in relationships, and HIV risk behaviours in men, as well as effective interventions, are urgently needed.

Adolescent↗
PubMed2004

The NEAT study: a 48-week open-label study to compare the antiviral efficacy and safety of GW433908 versus nelfinavir in antiretroviral therapy-naive HIV-1-infected patients.

OBJECTIVE: To compare the efficacy, durability, and tolerability of GW433908 (908), 1400 mg twice-daily (BID), with nelfinavir (NFV), 1250 mg BID. METHODS: This was an international, multicenter, randomized, open-label study (NEAT) in antiretroviral therapy (ART)-naive HIV-infected adults with plasma HIV-1 RNA (vRNA) at screening > or =5000 copies/mL (c/mL). Patients were randomly assigned to 908 or NFV (2:1) for a minimum of 48 weeks, with a background of abacavir (ABC) and lamivudine (3TC). RESULTS: A total of 166 patients received randomized treatment with 908 BID and 83 received NFV BID. The population was diverse with regard to race and gender (76% Hispanics and blacks, 31% female) and had advanced HIV disease at screening (45% had vRNA >100,000 c/mL, 48% had CD4 cell counts <200 cells/mm3, 20% had a history of Centers for Disease Control class C events). After 48 weeks of study by an intention-to-treat rebound or discontinuation = failure analysis, a greater proportion of patients in the 908 BID group (66%) than the NFV BID group (51%) achieved vRNA <400 c/mL. Furthermore, more patients with screening vRNA >100,000 c/mL (67 vs. 35%) or CD4 <50 cells/mm3 (48 vs. 24%) achieved undetectable viral loads taking 908 BID compared with NFV BID, respectively. Favorable immunologic responses were observed for both groups. Diarrhea, which was more common in the NFV BID group (18 vs. 5%), was the only drug-related grade 2-4 adverse event with a significant difference (P = 0.002) in incidence between groups. CONCLUSION: Administration of 908 BID resulted in a potent and sustained antiretroviral response, notably in ART-naive patients with advanced HIV disease. GW433908 was generally well tolerated and provides a convenient dosing option without food or fluid restrictions.

Adolescent↗
PubMed2004

Transactional sex among women in Soweto, South Africa: prevalence, risk factors and association with HIV infection.

Sex workers have long been considered a high-risk group for HIV infection, but to date little quantitative research has explored the association between HIV risk and exchange of sex for material gain by women in the general population. The objective of this study was to estimate the prevalence of such transactional sex among women attending antenatal clinics in Soweto, South Africa, to identify demographic and social variables associated with reporting transactional sex, and to determine the association between transactional sex and HIV serostatus. We conducted a cross-sectional study of women seeking antenatal care in four Soweto health centres who accepted routine antenatal HIV testing. Private face-to-face interviews covered socio-demographics, sexual history and experience of gender-based violence. 21.1% of participants reported having ever had sex with a non-primary male partner in exchange for material goods or money. Women who reported past experience of violence by male intimate partners, problematic substance use, urban residence, ever earning money, or living in substandard housing were more likely to report transactional sex, while women who reported delayed first coitus, were married, or had a post-secondary education were less likely to report transactional sex. Transactional sex was associated with HIV seropositivity after controlling for lifetime number of male sex partners and length of time a woman had been sexually active (OR = 1.54, 95% CI: 1.07, 2.21). Women who reported non-primary partners without transactional sex did not have increased odds of being HIV seropositive (OR = 1.04, 95% CI: 0.75, 1.43). We conclude that transactional sex may place women at increased risk for HIV, and is associated with gender-based violence, substance use and socio-economic disadvantage. Research, policy and programmatic initiatives should consider the role of transactional sex in women's HIV risk, with attention to the intersecting roles of violence, poverty, and substance use in shaping women's sexual behaviour.

Adolescent↗
PubMed2004

Age-related changes in expression of CXCR4 and CCR5 on peripheral blood leukocytes from uninfected infants born to human immunodeficiency virus type 1-infected mothers.

Cross-sectional analysis of human immunodeficiency virus-exposed, uninfected infants revealed high proportions of CXCR4-expressing cells in their cord blood, which declined at 4.5 months and increased between 9 and 15 months to levels approaching those of uninfected adults. Proportions of CCR5-expressing cells, however, were very low in cord blood and subsequently increased with age.

Adult↗
PubMed2003

Characterisation of near-full length genome sequences of three South African human immunodeficiency virus type 1 subtype C isolates.

As subtype C is the most prevalent circulating human immunodeficiency virus type 1 (HIV-1) subtype internationally as well as locally in South Africa, more information on the biological nature and molecular characteristics of these viruses is required. Proviral DNA was isolated from primary cultures of three South African R5 isolates and the near-full length genome amplified by PCR. The resultant PCR product was cloned into the pCR-XL-TOPO vector and a representative clone from each isolate sequenced by primer walking. Phylogenetic analysis showed all three clones clustered within subtype C with a bootstrap value of 100%, and no recombination with other subtypes was identified by distance scan and bootscan analysis. Analysis of the potential coding regions revealed premature truncations of the second rev exon but no other potential structural distortions nor frameshift mutations in the open reading frames. All the clones contained three potential NF-kappaB binding sites, a feature unique to subtype C viruses. The tips of the V3 loops contained the GPGQ sequence motif characteristic of CCR5-utilising subtype C strains, as well as relatively low overall net positive charge characteristic of non-syncytium-inducing isolates. This information contributes to our overall knowledge of circulating strains in South Africa and to the making of effective vaccines and chemotherapeutic agents.

Amino Acid Sequence↗