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The antiviral efficacy and the safety of once-daily atazanavir 400 mg, an azapeptide protease inhibitor (PI), is compared with efavirenz 600 mg, each in combination with open-label fixed-dose zidovudine plus lamivudine twice daily. The results suggest that for initial HIV treatment, a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as effective and well tolerated as the combination of efavirenz/zidovudine/lamivudine.

The patients' knowledge of HIV condition and its treatment are recognized as a factor that influences adherence to antiretroviral therapy, and can be improved through educational programs. An educational intervention improves adherence to antiretroviral regimens and health status and hence should be initiated early in therapy.

The efficacy and safety of 24 weeks of treatment with the fusion inhibitor enfuvirtide in combination with an optimized background antiretroviral regimen was compared with the efficacy and safety of the optimized background regimen alone. It was concluded that the addition of enfuvirtide to an optimized background regimen provided significant viral suppression and immunologic benefit over a 24-week period in HIV-1-infected patients who had previously received multiple antiretroviral drugs.

Pregnant women with HIV infection do not need to take nevirapine if they are already taking zidovudine or other AIDS drugs. These drugs are used to prevent the virus from passing to the baby during childbirth. In a study of 1,170 women, nevirapine did not lower the risk of transmission more than traditional AIDS drugs do., Context: A 2-dose intrapartum/newborn nevirapine regimen reduced perinatal human immunodeficiency virus (HIV) transmission in Ugandan women not receiving antenatal antiretroviral therapy (ART). However, it is unknown whether the addition of the 2-dose nevirapine regimen to standard ART would further reduce perinatal HIV transmission. Objective: To determine whether a 2-dose nevirapine regimen can decrease perinatal transmission of HIV in nonbreastfeeding women receiving standard ART. Design and Setting: International, blinded, placebo-controlled, phase 3 trial enrolling women between May 1997 and June 2000 at clinical sites providing care for HIV infection throughout the United States, Europe, Brazil, and the Bahamas. Participants: A total of 1270 women received nevirapine (n=642) or placebo (n=628). Infants were followed up for 6 months to determine HIV-infection status, which was available for 1248 deliveries. Intervention: A 200-mg dose of oral nevirapine to women after onset of labor and a 2-mg/kg dose of oral nevirapine to newborns between 48 and 72 hours after birth. Main Outcome Measures: Detection of HIV infection in infants and grade 3 and 4 toxic effects in women and newborns. Results: After review by the data and safety monitoring board, the trial was stopped early because the overall transmission rates were significantly lower than assumed for the study design. Antenatal ART included zidovudine alone in 23%; combinations without protease inhibitors in 36%; and combinations with protease inhibitors in 41%. Thirty-four percent of women had elective cesarean delivery. No significant safety concerns were identified for women or infants. Detection of HIV infection occurred in 9 (1.4%; 95% confidence interval [CI], 0.6%-2.7%) of 631 nevirapine group deliveries and 10 (1.6%; 95% CI, 0.8%-2.9%) of 617 placebo group deliveries. The 95% CI for the difference in transmission rate (-0.2) between the 2 study arms ranged from -1.5% in favor of nevirapine to 1.2% in favor of placebo (P=.82, Fisher exact test). The transmission rate was higher in women with lower baseline CD4 cell counts and higher delivery HIV RNA levels, but there was no significant difference between treatment arms in any sub group. Conclusion: Risk of perinatal HIV transmission was low and no benefit from additional intrapartum/newborn nevirapine was demonstrated when women received prenatal care and antenatal ART, and elective cesarean section was made available.

Quadruple therapy with saquinavir, nelfinavir and two nucleoside reverse transcriptase inhibitors appears to be more effective in treating HIV infection than triple therapy with only one protease inhibitors. Nelfinavir inhibits an enzyme that metabolizes protease inhibitors, leading to increased blood levels of the drug.

Having the CCR2B-64I receptor does not appear to protect children from HIV infection. In a study of 745 children born to HIV-infected women, this receptor was just as likely to occur in HIV-infected children as in non-infected children.

Protease inhibitors may prevent cytomegalovirus retinal infection in many HIV patients and may slow the progression of existing retinal disease. This was the conclusion of a study of 93 HIV patients taking highly active antiretroviral therapy, which includes the use of protease inhibitors.

HIV patients may need to take triple-drug therapy for many years to suppress viral reproduction. Triple-drug therapy usually includes a protease inhibitor plus two other AIDS drugs. Researchers randomly assigned 279 HIV patients whose blood virus levels became undetectable after two months of triple-drug therapy to continue triple-drug therapy or take two of the drugs only. Viral levels rose again in about one-third of the patients taking two drugs, but this happened in only 10% of those who continued taking all three drugs.

Zidovudine and elective cesarean delivery may significantly reduce the risk of HIV transmission during childbirth by HIV-infected women. Researchers studied factors influencing HIV transmission among 2,834 infants and their HIV-positive mothers. Zidovudine antiviral medication was used by 902 women to reduce the risk of HIV transmission. HIV was transmitted to infants by 17% of women not taking zidovudine and 6% of treated women. Cesarean delivery was not protective when zidovudine was not used, but the rate of HIV transmission was lower in drug-treated women delivered by cesarean.

Zidovudine and elective cesarean delivery may significantly reduce the risk of HIV transmission during childbirth by HIV-infected women. Researchers studied factors influencing HIV transmission among 2,834 infants and their HIV-positive mothers. Zidovudine antiviral medication was used by 902 women to reduce the risk of HIV transmission. HIV was transmitted to infants by 17% of women not taking zidovudine and 6% of treated women. Cesarean delivery was not protective when zidovudine was not used, but the rate of HIV transmission was lower in drug-treated women delivered by cesarean.

Zidovudine and elective cesarean delivery may significantly reduce the risk of HIV transmission during childbirth by HIV-infected women. Researchers studied factors influencing HIV transmission among 2,834 infants and their HIV-positive mothers. Zidovudine antiviral medication was used by 902 women to reduce the risk of HIV transmission. HIV was transmitted to infants by 17% of women not taking zidovudine and 6% of treated women. Cesarean delivery was not protective when zidovudine was not used, but the rate of HIV transmission was lower in drug-treated women delivered by cesarean.

Zidovudine and elective cesarean delivery may significantly reduce the risk of HIV transmission during childbirth by HIV-infected women. Researchers studied factors influencing HIV transmission among 2,834 infants and their HIV-positive mothers. Zidovudine antiviral medication was used by 902 women to reduce the risk of HIV transmission. HIV was transmitted to infants by 17% of women not taking zidovudine and 6% of treated women. Cesarean delivery was not protective when zidovudine was not used, but the rate of HIV transmission was lower in drug-treated women delivered by cesarean.

A genetic mutation which may protect adults against HIV infection might not prevent infection of infants born to HIV-infected mothers. A variant of the CCR5 chemokine receptor gene might prevent HIV from infecting cells. Researchers in France studied the gene in 512 children born to HIV-positive mothers. About 10% of both infected and non-infected children had the mutation. Children with the mutation were less likely to have developed serious HIV-related diseases by age 3. This mutation does not prevent mother-to-child HIV transmission, but it may slow disease progression., Context.--Studies suggest that adults with the CCR5[Delta]32 deletion are less likely to become infected with the human immunodeficiency virus (HIV) and to develop HIV-related disease progression, but the effect of the mutation in children is not known. Objective.--To study the effect of the CCR5 chemokine receptor mutant allele on mother-to-child transmission of HIV type 1 (HIV-1) and subsequent disease progression in infected children. Design.--Multicenter, prospective study of infants born to mothers seropositive for HIV-1. Setting.--A total of 52 medical centers participating in the French Pediatric HIV Cohort studies. Participants.--The CCR5[Delta]32 deletion was studied in 512 non-African children, born between 1983 and 1996 to HIV-1--infected mothers. Among them, 276 children were infected and 236 were not. Main Outcome Measures.--HIV-1 infection status and, in infected children followed up since birth, incidence of category B and C disease events and severe immunosuppression as defined in the new pediatric Centers for Disease Control and Prevention (CDC) classification, according to CCR5 genotype. Results.--The 32-base pair deleted allele was detected at a frequency of 0.05. Only 1 infant, not infected by HIV-1, was homozygous for the [Delta]32 deletion. The 49 heterozygous children (9.6% of the total; 95% confidence interval [CI], 7.1-12.2) were equally distributed into the infected (9.8%) and uninfected (9.3%) groups. The incidence of stage C symptoms in heterozygous infected children was 9% at 36 months vs 28% in children homozygous for the normal allele (P

Zidovudine treatment of pregnant women who are HIV-positive may prevent transmission of HIV infection to their infants. Among 409 pregnant women infected with HIV, 205 were treated with zidovudine and 204 received a placebo. The women were between 14 and 34 weeks' gestation and all had CD4+ T-lymphocyte counts above 200. The women in the zidovudine group took 100 milligrams (mg) orally five times a day before birth and received intravenous zidovudine during labor. Their infants were also treated with zidovudine for six weeks. Among 180 infants in the zidovudine group for whom results were known, 13 tested positive for HIV, compared to 40 among 183 infants in the placebo group. The estimated proportions of infants infected at 18 months were 8.3% in the zidovudine group and 25.5% in the placebo group. This indicates that zidovudine treatment can reduce the risk of HIV transmission from mother to infant by approximately two-thirds.

Disease in infants infected with HIV at birth may be associated with the severity of disease in the mother at the time of delivery. Among 162 HIV-infected infants, the risk of opportunistic infections was about 13% at 18 months and 15% at 36 months. The risk of brain disease was about 10% at 18 months and 11% at 36 months. The risk of either complication at 18 months was 50% among infants born to mothers with advanced disease at delivery and 14% among those born to mothers with less severe disease. Of the infants whose mothers had advanced disease, 44% died before 18 months, compared to 9% of infants whose mothers had less advanced disease. The risk of illnesses and the risk of death was higher among infants whose mothers had HIV-1 antigens, or substances that initiate immune responses to HIV. Thirty-one percent of infants whose mothers had HIV-1 antigens also had detectable antigens, compared to 7% of infants whose mothers did not have antigens.

Abstract Background The evolution of plasma viral load after HIV infection has been described as reaching a setpoint, only to start rising again shortly before AIDS diagnosis. In contrast, CD4 T-cell count is considered to show a stable decrease. However, characteristics of marker evolution over time depend on the scale that is used to visualize trends. In reconsidering the setpoint theory for HIV RNA, we analyzed the evolution of CD4 T-cell count and HIV-1 RNA level from HIV seroconversion to AIDS diagnosis. Follow-up data were used from two cohort studies among homosexual men (N = 400), restricting to the period before highly active antiretroviral therapy became widely available (1984 until 1996). Individual trajectories of both markers were fitted and averaged, both from seroconversion onwards and in the four years preceding AIDS diagnosis, using a bivariate random effects model. Both markers were evaluated on a scale that is directly related to AIDS risk. Results Individuals with faster AIDS progression had higher HIV RNA level six months after seroconversion. For CD4 T-cell count, this ordering was less clearly present. However, HIV RNA level and CD4 T-cell count showed qualitatively similar evolution over time after seroconversion, also when stratified by rate of progression to AIDS. In the four years preceding AIDS diagnosis, a non-significant change in HIV RNA increase was seen, whereas a significant biphasic pattern was present for CD4 T-cell decline. Conclusion HIV RNA level has more setpoint behaviour than CD4 T-cell count as far as the level shortly after seroconversion is concerned. However, with respect to the, clinically more relevant, marker evolution over time after seroconversion, a setpoint theory holds as much for CD4 T-cell count as for HIV RNA level.

The AIDS drug combination zidovudine-lamivudine can substantially reduce the risk of HIV transmission from a pregnant woman to her child but the treatment has substantial side effects and the virus can become resistant. This was the conclusion of a study of 455 HIV-infected pregnant women who received the drug combination and 899 who had received zidovudine alone.

Human immunodeficiency virus (HIV) enters cells in vitro via CD4 and a coreceptor. Which of 15 known coreceptors are important in vivo is poorly defined but may be inferred from disease-modifying mutations, as for CCR5. Here two single nucleotide polymorphisms are described in Caucasians in [CX.sub.3]CR1, an HIV coreceptor and leukocyte chemotactic/adhesion receptor for the chemokine fractalkine. HIV-infected patients homozygous for [CX.sub.3]CR1-1249 M280, a variant haplotype affecting two amino acids (isoleucine-249 and methionine-280), progressed to AIDS more rapidly than those with other haplotypes. Functional [CX.sub.3]CR1 analysis showed that fractalkine binding is reduced among patients homozygous for this particular haplotype. Thus, [CX.sub.3]CR1-1249 M280 is a recessive genetic risk factor in HIV/AIDS., The risk of HIV infection and the rate of HIV disease progression are both highly variable in populations, but factors responsible for this variability remain poorly defined. Mutations in genes [...]