Maternal HIV-1 DNA load and mother-to-child transmission

While many factors contribute to mother-to-child transmission (MTCT) of HIV-1, maternal plasma HIV-1 RNA viral load (RNA-VL) has been consistently found as the main risk factor, including when antiretroviral prophylaxis was used to prevent MTCT. However the predictive value of RNA-VL is poor. A recent study of HIV-1-positive pregnant women who did not receive antiretroviral prophylaxis reported an association between HIV-1 DNA viral load (DNA-VL) and MTCT that was stronger than the association between RNA-VL and MTCT. We sought to determine if HIV-1 DNA-VL was independently associated with MTCT of HIV in a population of women who received zidovudine prophylaxis during pregnancy and whose infants received zidovudine after birth. Patients were 33 non-breastfeeding transmitting (TR) and 33 nontransmitting mothers (NTR) from Perinatal HIV Prevention Trial (PHPT-1), a multicenter clinical trial conducted in Thailand comparing zidovudine prophylaxis durations to prevent MTCT. TR and NTR mothers were matched according to baseline RNA-VL. Maternal peripheral blood mononuclear cell (PBMC)-associated HIV-1 DNA was extracted from whole blood, and DNA-VL was established by quantitative real-time polymerase chain reaction. We found that TR had a significantly higher cell-associated HIV-1 DNA viral load than did NTR. Median TR DNA-VL was 2.54 log(10) copies per microgram PBMC DNA, while it was 2.28 log(10) copies per microgram PBMC DNA in NTR (Wilcoxon p = 0.02). In summary, HIV-1 DNA viral load was associated with MTCT in a population of women who received antiretroviral prophylaxis during pregnancy, independently from RNA viral load.     

Is there a difference in the efficacy of peripartum antiretroviral regimens in reducing mother-to-child transmission of HIV in Africa?

BACKGROUND: Peripartum antiretroviral regimens have been shown to prevent mother-to-child transmission of HIV (MTCT) in randomized clinical trials; however, direct comparison of published results is impossible given methodological and population differences. OBJECTIVE: To directly compare the efficacy of different antiretroviral regimens in reducing the risk of 6-week MTCT rate in African breastfeeding populations. METHODS: Pooled analysis including all mother-infant pairs from any relevant trial: West African ZDV-placebo trials, Petra ZDV+3TC [two regimens A (pre/intra/post-partum) and B (intra/post-partum), placebo from Uganda and Tanzania], SAINT (NVP and Petra arm B), HIVNET012 (NVP, ultra short ZDV pp) and the Vitamin A trial (as placebo arm in South Africa). Peripartum HIV infection was any positive RNA or DNA polymerase chain reaction test < day 60. The MTCT risk was estimated at 6 weeks for each treatment arm and compared with placebo or single-dose NVP using logistic regression adjusting for maternal CD4 cell count, breastfeeding and birthweight. RESULTS: Overall, 4125 singleton live-births were included; 3629 (88%) were assessed for HIV status at 6 weeks of age. In comparison with placebo, zidovudine + lamivudine (ZDV+3TC) arm A [adjusted odds ratio (AOR), 0.23; P < 0.0001], ZDV+3TC arm B (AOR, 0.49; P < 0.001), antenatal ZDV short (AOR, 0.55; P = 0.006) and nevirapine (NVP) (AOR, 0.60; P = 0.0007) significantly reduced MTCT. In comparison with NVP, only the longest regimen of ZDV+3TC (AOR, 0.39, P < 0.0005) was significantly more effective. CONCLUSION: These results are in line with current World Health Organisation guidelines suggesting equivalence of choice between single-dose NVP and short-course ZDV, and confirm the greater efficacy of ZDV+3TC than with any single antiretroviral drug.     

Effect of perinatal zidovudine prophylaxis on the evolution of cell-free HIV-1 RNA in breast milk and on postnatal transmission

Perinatal zidovudine (ZDV) prophylaxis decreases rates of perinatal transmission of human immunodeficiency virus type 1 (HIV-1). Its relationship with levels of HIV-1 RNA in breast milk and postnatal transmission in breast-fed African children is unknown. At day 8 after delivery, levels of HIV-1 RNA in breast milk from 28 women who transmitted HIV-1 (Ts) postnatally and from 130 women who did not transmit HIV-1 (NTs) were lower for women receiving ZDV than for women receiving placebo. Levels of HIV-1 RNA in breast milk remained low over time in NTs but increased by 8-16-fold in Ts treated with ZDV from baseline to days 45/90 after delivery. Levels of HIV-1 RNA in breast milk at day 8 after delivery and the increase in levels of HIV-1 RNA in breast milk from day 8 to days 45/90 after delivery were independently associated with postnatal transmission. An increase in the levels of HIV-1 RNA in breast milk from day 8 to 45 after delivery was associated with maternal ZDV prophylaxis. The rebound in levels of HIV-1 RNA in breast milk after discontinuation of maternal antiretrovirals needs to be further explored--it may justify prolonging antiretroviral prophylaxis during the entire breast-feeding period.     

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.     

Exposure to HIV-1 during delivery and mother-to-child transmission

BACKGROUND: The correlation between the presence of HIV-1 in maternal cervicovaginal secretions and in the infant's oro-pharyngal secretions at birth, and mother-to-child HIV transmission (MTCT) were examined to obtain a better understanding of its mechanism. METHODS: Women without medical and obstetrical complications, living within a reasonable distance of the government hospital in Mombasa, Kenya, were recruited after informed consent. Maternal and infant characteristics were collected. Polymerase chain reaction was used to detect HIV-1 in cervico-vaginal and oro-pharyngal secretions. Infants were tested for HIV-1 by polymerase chain reaction within 48 h and at 6 weeks after delivery. RESULTS: Between April 1998 and April 1999, 228 woman-infant pairs were included in the study. HIV-1 DNA in cervico-vaginal secretions was independently associated with HIV-1 maternal viral load and with infant birth-weight, whereas HIV-1 RNA was associated with maternal viral load and maternal age. HIV-1 DNA in the oropharyngal secretions was also independently associated with maternal viral load. MTCT rate at the age of 6 weeks was 23.6%. Intrapartum and early postpartum HIV transmission was independently associated with maternal viral load [adjusted odds ratio (OR), 1.6; 95% confidence interval (CI),1.0-2.7], detection of HIV-1 RNA in cervico-vaginal secretions (adjusted OR, 3.2; 95% CI, 1.5-7.3) and of HIV-1 DNA in oro-pharyngeal secretions (adjusted OR, 3.2; 95% CI, 1.1-9.0). DISCUSSION: As far as is known, this is the first study showing that infant exposure to HIV-1 in the birth canal and the presence of HIV-infected cells in the infant's oropharyngeal cavity are independently associated with intrapartum and early postpartum MTCT. It supports the hypothesis that MTCT could occur through the oral route.     

Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group

BACKGROUND: Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. OBJECTIVES: In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. METHODS: Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and na?ve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). RESULTS: Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of na?ve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the na?ve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of na?ve CD4+ T cells at baseline resulted in modest long-term na?ve T-cell recovery. CONCLUSIONS: Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Na?ve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported for immune recovery in adults after chemotherapy and bone marrow transplantation.     

Maternal syphilis infection is associated with increased risk of mother-to-child transmission of HIV in Malawi

OBJECTIVE: To determine the association between maternal syphilis and HIV mother-to-child transmission (MTCT). DESIGN: Prospective cohort study. METHODS: Pregnant women admitted at Queen Elizabeth Central Hospital (Malawi) in late third trimester were screened for HIV (by HIV rapid tests) and syphilis (by rapid plasma regain test and Treponema pallidum hemagglutination assay). HIV-infected women and their infants received nevirapine, according to the HIVNET 012 protocol. They were followed up at 6 and 12 weeks postpartum. Infant HIV infection was diagnosed by DNA PCR. FINDINGS: Of the 1155 HIV-infected women enrolled, 1147 had syphilis test results, of whom 92 (8.0%) were infected. Only 751 HIV-positive women delivered live singleton infants who were tested for HIV at birth. Of these, 65 (8.7%) were HIV-infected, suggesting in utero (IU) HIV MTCT. Of the 686 infants who were HIV-negative at birth, 507 were successfully followed up. Of these, 89 (17.6%) became HIV-infected, suggesting intrapartum/postpartum (IP/PP) HIV MTCT. Maternal syphilis was associated with IU HIV MTCT, after adjusting for maternal log10 HIV-1 viral load and low birth weight (LBW) [adjusted relative risk (ARR), 2.77; 95% CI, 1.40-5.46]. Furthermore, maternal syphilis was associated with IP/PP HIV MTCT (ARR, 2.74; 95% CI, 1.58-4.74), after adjusting for recent fever, breast infection, LBW and maternal log10 HIV-1 viral load. CONCLUSION: Maternal syphilis is associated with IU and IP/PP HIV MTCT. Screening and early treatment of maternal syphilis during pregnancy may reduce pediatric HIV infections.     

Maternal viral load and hepatitis B virus mother‐to‐child transmission risk: A systematic review and meta‐analysis

Aim

The aim of this study was to assess the relationship between maternal viral load and mother‐to‐child transmission (MTCT) risk in hepatitis B envelope antigen (HBeAg)‐positive mothers.

Methods

PubMed and Web of Science were systematically searched. We compared MTCT incidence between maternal hepatitis B virus (HBV)‐DNA‐positive and HBV‐DNA‐negative groups. We also examined the dose–response effect of this relationship.

Results

Twenty‐one studies with 10 142 mother–child pairs were included in the studies. The mean MTCT incidence was 13.1% in the maternal HBV‐DNA‐positive group, compared with 4.2% in the negative group. The summary MTCT odds ratio of maternal HBV‐DNA positive compared with negative was 9.895 (95% confidence interval [CI], 5.333 to 18.359; Z = 7.27, P < 0.00001) by random‐effects model. In maternal HBV‐DNA <6 log10 copies/mL, 6–8 log10 copies/mL, and >8 log₁₀ copies/mL level stratifications, the pooled MTCT incidences were 2.754% (95% CI, 1.198–4.310%; Z = 3.47, P = 0.001), 9.932% (95% CI, 6.349–13.516%; Z = 5.43, P < 0.00001), and 14.445% (95% CI, 8.317–20.572%; Z = 4.62, P < 0.00001), respectively. A significant linear dose–response association was found between maternal viral load and MTCT risk, with the points estimate of increased MTCT risk 2.705 (95% CI, 1.808–4.047) at 6 log10 copies/mL compared with reference (3 log10 copies/mL), and 7.316 (95% CI, 3.268–16.378) at 9 log₁₀ copies/mL. A significant non‐linear dose–response association was also found between maternal viral load and HBV MTCT risk (model χ² = 23.43, P < 0.00001).

Conclusion

Our meta‐analysis indicated that maternal viral load was an important risk factor for MTCT in HBeAg‐positive mothers, and maternal viral load was dose‐dependent with HBV MTCT incidence.     

Laboratory indicators of mastitis are not associated with elevated HIV-1 DNA loads or predictive of HIV-1 RNA loads in breast milk

BACKGROUND: Mother-to-child transmission (MTCT) of HIV-1 has been associated with symptomatic and asymptomatic mastitis and with the quantity of HIV-1 RNA and DNA in maternal milk. An improved understanding of the relationship between indicators of inflammation and HIV-1 loads in breast milk could improve MTCT prevention strategies. METHODS: In a cross-sectional study, laboratory indicators of mastitis (breast milk sodium [Na(+)] concentration, sodium : potassium ratio [Na(+) : K(+)], and leukocyte count) were related to breast milk HIV-1 RNA and DNA loads and were evaluated for predicting viral loads in milk. RESULTS: Mastitis was present in 63 (15%) of 407, 60 (15%) of 407, and 76 (18%) of 412 milk specimens, as defined by Na(+) concentration >12 mmol/L, Na(+) : K(+) >1, and total leukocyte counts > or =10(6) cells/mL, respectively. Each indicator was associated with an increased milk HIV-1 RNA load (P<.05) but not with HIV-1 DNA load. Neutrophils correlated better with milk HIV-1 RNA load than total leukocytes. However, neither neutrophil count, Na(+) concentration, nor Na(+) : K(+) displayed a threshold that was both sensitive and specific for the detection of HIV-1 RNA in milk at thresholds of > or =50 or > or =10(4) copies/mL. CONCLUSIONS: HIV-1 DNA loads in breast milk were not increased during mastitis. Neither milk cell counts nor electrolyte concentrations were useful predictors of milk HIV-1 RNA or DNA loads for individual women.     

Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group Protocol 306 Investigators.

OBJECTIVE: To study the antiviral activity of lamivudine (3TC) plus zidovudine (ZDV), didanosine (ddl), or stavudine (d4T). DESIGN: Randomized, placebo-controlled, partially double-blinded multicenter study. SETTING: Adult AIDS Clinical Trials Units. PATIENTS: Treatment-naive HIV-infected adults with 200-600x10(6) CD4 T lymphocytes/l. INTERVENTIONS: Patients were openly randomized to a d4T or a ddl limb, then randomized in a blinded manner to receive: d4T (80 mg/day), d4T plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos; or ddl (400 mg/day), ddl plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos. After 24 weeks 3TC was added for patients assigned to the monotherapy arms. MAIN OUTCOME MEASURE: The reduction in plasma HIV-1 RNA level at weeks 24 and 48.RESULTS: Two hundred ninety-nine patients were enrolled. After 24 weeks the mean reduction in plasma HIV-1 RNA copies/ml from baseline was 0.49 log10 (d4T monotherapy) versus 1.03 log10 (d4T plus 3TC; P = 0.001), and 0.68 log10 (ddl monotherapy) versus 0.82 log10 (ddl plus 3TC; P>0.22). After 48 weeks the mean reduction was 1.08 log10 (d4T plus 3TC) versus 1.01 log10 (ZDV plus 3TC) in the d4T limb (P = 0.66), and 0.94 log10 (ddl plus 3TC) versus 0.88 log10 (ZDV plus 3TC; P = 0.70) in the ddl limb. CONCLUSIONS: 3TC added significantly to the virologic effects of d4T, but not ddl, in treatment-naive patients. 3TC plus d4T produced virologic changes comparable to those of 3TC plus ZDV. These results support the use of 3TC with either ZDV or d4 as a component of initial combination antiretroviral therapy.     

Reduced mother-to-child transmission of HIV associated with infant but not maternal GB virus C infection

BACKGROUND: Prolonged coinfection with GB virus C (GBV-C) has been associated with improved survival in human immunodeficiency virus (HIV)-infected adults. We investigated whether maternal or infant GBV-C infection was associated with mother-to-child transmission (MTCT) of HIV-1 infection. METHODS: The study population included 1364 HIV-infected pregnant women enrolled in 3 studies of MTCT of HIV in Bangkok, Thailand (the studies were conducted from 1992-1994, 1996-1997, and 1999-2004, respectively). We tested plasma collected from pregnant women at delivery for GBV-C RNA, GBV-C antibody, and GBV-C viral genotype. If GBV-C RNA was detected in the maternal samples, the 4- or 6-month infant sample was tested for GBV-C RNA. The rates of MTCT of HIV among GBV-C-infected women and infants were compared with the rates among women and infants without GBV-C infection. RESULTS: The prevalence of GBV-C RNA in maternal samples was 19%. Of 245 women who were GBV-C RNA positive, 101 (41%) transmitted GBV-C to their infants. Of 101 infants who were GBV-C RNA positive, 2 (2%) were infected with HIV, compared with 162 (13%) of 1232 infants who were GBV-C RNA negative (odds ratio [OR] adjusted for study, 0.13 [95% confidence interval {CI}, 0.03-0.54]). This association remained after adjustment for maternal HIV viral load, receipt of antiretroviral prophylaxis, CD4(+) count, and other covariates. MTCT of HIV was not associated with the presence of GBV-C RNA (adjusted OR [aOR], 0.94 [95% CI, 0.62-1.42]) or GBV-C antibody (aOR, 0.90 [95% CI, 0.54-1.50]) in maternal samples. CONCLUSIONS: Reduced MTCT of HIV was significantly associated with infant acquisition of GBV-C but not with maternal GBV-C infection. The mechanism for this association remains unknown.     

Mother-to-child transmission of HIV-1: association with malaria prevention, anaemia and placental malaria

Objectives

Malaria infection may impact on mother‐to‐child transmission (MTCT) of HIV‐1. Prevention of malaria in pregnancy could thus potentially affect MTCT of HIV. We studied the impact of intermittent preventive treatment during pregnancy (IPTp) on HIV‐1 MTCT in southern Mozambique.

Methods

A total of 207 HIV‐positive Mozambican pregnant women were enrolled in the study as part of a randomized placebo‐controlled trial of two‐dose sulfadoxine‐pyrimethamine (SP) IPTp in women receiving single‐dose nevirapine to prevent MTCT of HIV. HIV RNA viral load, maternal anaemia and peripheral and placental malaria were assessed at delivery. Infant HIV status was determined by DNA polymerase chain reaction (PCR) at 1 month of age.

Results

There were 19 transmissions of HIV in 153 mother–infant pairs. IPTp with SP did not have a significant impact on MTCT (11.8% in the SP group vs. 13.2% in the placebo group; P=0.784) or on maternal HIV RNA viral load [16 312 (interquartile range {IQR} 4076–69 296) HIV‐1 RNA copies/mL in the SP group vs. 18 274 (IQR 5471–74 104) copies/mL in the placebo group; P=0.715]. In multivariate analysis, maternal HIV RNA viral load [adjusted odds ratio (AOR) 19.9; 95% confidence interval (CI) 2.3–172; P=0.006] and anaemia (haematocrit <33%; AOR 7.5; 95% CI 1.7–32.4; P=0.007) were independent risk factors for MTCT. Placental malaria was associated with a decrease in MTCT (AOR 0.23; 95% CI 0.06–0.89; P=0.034).

Conclusions

IPTp with SP was not associated with a significant impact on MTCT of HIV. Maternal anaemia was an independent risk factor for MTCT.     

Genetic diversity of HIV-1 in western Kenya: subtype-specific differences in mother-to-child transmission

BACKGROUND: Little is known about the impact of HIV-1 group M subtypes on mother-to-child transmission (MTCT) of HIV-1 in African settings where multiple HIV-1 group M subtypes are co-circulating. OBJECTIVE: To assess the role of subtype variation on MTCT. METHODS: HIV-1-infected women attending an antenatal clinic in western Kenya were enrolled for a prospective study (1996-2000) of MTCT. HIV-1 subtype analysis of p24gag and gp41env identified potential recombinants, and their role in MTCT was determined. RESULTS: Among 414 women for whom HIV-1 subtype and HIV transmission status were available, MTCT occurred in 80 (19.3%). MTCT rates were higher among women with subtype D compared with subtype A in either the gp41 region [31.6 versus 16.1%, relative risk (RR) 2.0, P=0.002] or p24 region (29.9 versus 18.0%, RR 1.7, P=0.02). Discordant subtype combinations were identified in 103 of the women (25.9%), and were associated with higher rates of MTCT (28.2 versus 17.0%, RR 1.7, P=0.01). In multivariate analysis, women with subtype combinations D/D, D/A, and A/D had an increased risk of MTCT (adjusted odds ratios 3.5, 2.5, 6.2; P=0.005, 0.05, and 0.0003, respectively) compared with A/A women after adjustment for maternal HIV viral load, placental malaria infection, episiotomy or perineal tear, and low birthweight. CONCLUSION: MTCT appears to be more common among mothers infected with subtype D compared with subtype A. Such differences in MTCT frequency may be caused by altered cellular tropism for placental cell types.     

Postnatal transmission of HIV-1 after a maternal short-course zidovudine peripartum regimen in West Africa

BACKGROUND: To assess the postnatal transmission (PT) risk of HIV-1 after a maternal short-course zidovudine regimen in a breastfeeding population. METHODS: Data were pooled from two trials: ANRS 049a DITRAME (Abidjan, C?te d'Ivoire and Bobo-Dioulasso, Burkina-Faso) and RETROCI (Abidjan). Consenting HIV-1 seropositive women were randomized at 36-38 weeks' gestation between September 1995 and February 1998, to receive oral zidovudine or placebo: one tablet twice daily until delivery, and in DITRAME only, for 7 more days. A PT case was infection in a child with a negative HIV-1 PCR at age >/= 30 days who later became infected as defined by a positive HIV-1 PCR, or if aged >/= 15 months, a positive HIV serology. Cumulative risks (CR) of PT were computed using a competing risk approach with weaning as a competing event. FINDINGS: At age 24 months, CR for PT were similar in the zidovudine (9.8%, n = 254) and placebo groups (9.1%, n = 225). In a multivariate model of PT risk factors, the treatment effect was not significant, maternal CD4 cell count < 500 x 10(6)/l at entry tripled the hazard compared to women with CD4 cell counts >/= 500 x 10(6)/l [hazard ratio (HR), 3.14; 95% confidence interval (CI), 1.31-7.49] as well as an increased maternal plasma viral load at entry (HR, 2.65 for 1 log(10) increase; CI, 1.75-4.00). INTERPRETATION: PT occurred at a similar rate between arms and therefore reduced the long-term overall efficacy of this peripartum zidovudine regimen at age 24 months. The higher risk of PT among women with low CD4 cell count emphasizes the importance of identifying interventions to prevent PT for these women.     

Stavudine in zidovudine (ZDV)-experienced compared with ZDV-naive patients

OBJECTIVE: To assess the effect of prior zidovudine (ZDV) use on subsequent response to stavudine (D4T)-containing regimens. DESIGN: Analysis of data from prospective observational database. METHODS: Patients were ZDV-experienced if they had previously received more than 90 days of ZDV and ZDV-naive if they had never received ZDV. HIV-1 RNA and CD4 cell counts were compared at 3, 6, and 12 months after initiation of D4T. Univariate and multivariate analyses were performed, adjusting for baseline HIV-1 RNA and CD4 cell count, age, sex, race, HIV transmission category, time since enrollment, and protease inhibitor use. RESULTS: No difference was found between ZDV-experienced (n = 130) and naive (n = 98) patients in age, sex, race, transmission category, use of a concurrent protease inhibitor, or baseline CD4 cell count and HIV-1 RNA. There was no difference in the median decline in HIV-1 RNA (-1.29 log10 copies/ml for experienced patients versus -1.19 log10 copies/ml for naive patients; P = 0.39), in achieving HIV-1 RNA < 400 copies/ml at 3 months (51% versus 49%; P = 0.79) or 6 months (48% versus 56%; P = 0.33). There was no difference in CD4 cell response (+73 x 10(6)/l versus + 87 x 10(6)/l; P = 0.51). By multivariate adjustment in a repeated measures analysis, there was no significant difference in achieving undetectable HIV-1 RNA or in CD4 cell response between experienced and naive patients. CONCLUSION: No difference in response to a D4T-containing regimen between ZDV-experienced and naive patients was found over a 1-year period. In contrast to previous trials, most patients in this study also received a protease inhibitor. These findings may be more relevant in the current era of highly active antiretroviral therapy.     

Differences in HIV-2 plasma viral load and immune activation in HIV-1 and HIV-2 dually infected persons and those infected with HIV-2 only in Abidjan, Côte D'Ivoire

OBJECTIVE: To determine whether blood plasma levels of HIV-2 RNA viral loads and immune activation markers differ between persons infected with HIV-2 only and those dually infected with HIV-1 and HIV-2. METHODS: Between September 1996 and February 2000, we collected, analyzed and compared levels of HIV-2 RNA in plasma and immune activation markers among 52 persons infected with HIV-2 alone and 75 with confirmed dual infection. We also compared viral load and immune activation in patients who were infected with HIV-1 only and those who were dually infected. RESULTS: When we conducted a CD4 T-cell count-stratified multivariate analysis of HIV-2 viral load, controlling for difference in CD4 T-cell counts, age and sex: at < 200 x 10 CD4 T cells/l, HIV-2 viral load was 2.0 log10 copies/ml lower in dually infected patients than in HIV-2 only patients (P < 0.0001). At CD4 T-cell counts between 200 x 10 and 500 x 10/l, HIV-2 viral load was 0.3 log10 copies/ml lower in dually infected patients (P = 0.45). However, at CD4 T-cells counts > 500 x 10/l, HIV-2 viral load was 0.9 log10 copies/ml higher in dually infected patients (P < 0.0001). Dually infected persons with undetectable HIV-2 viral loads had significantly higher median levels of CD8 T cells expressing CD38 (P < 0.001) and HLA-DR (P = 0.01) than HIV-2 only infected patients. CONCLUSION: These results suggest that in dual infection, the level of HIV-2 replication depends on the immune status of the patients, with HIV-1 out-replicating HIV-2 as disease progress.     

Twenty-four month efficacy of a maternal short-course zidovudine regimen to prevent mother-to-child transmission of HIV-1 in West Africa

OBJECTIVE: To assess the 24 month efficacy of a maternal short-course zidovudine regimen to prevent mother-to-child transmission (MTCT) of HIV-1 in a breastfeeding population in West Africa. METHODS: Data were pooled from two clinical trials: DITRAME-ANRS049a conducted in Abidjan, C?te d'Ivoire and Bobo-Dioulasso, Burkina-Faso and RETRO-CI, conducted in Abidjan. Between September 1995 and February 1998, consenting HIV-1-seropositive women were randomly assigned to receive zidovudine (300 mg) or placebo: one tablet twice daily from 36-38 weeks' gestation until delivery, then in DITRAME only, for 7 more days. Paediatric HIV-1 infection was defined as a positive HIV-1 polymerase chain reaction, or if aged > or =15 months, a positive HIV-1 serology. Cumulative risks (CR) of infection were estimated using a competing risk approach with weaning as a competing event. RESULTS: Among 662 live-born children, 641 had at least one HIV-1 test. All but 12 children were breastfed. At 24 months, overall CR of MTCT were 0.225 in the zidovudine and 0.302 in the placebo group, a 26% significant reduction. Among children born to women with CD4 cell counts < 500/ml at enrollment, CR of MTCT were similar, 0.396 in the zidovudine and 0.413 in the placebo group. Among children born to women with CD4 cell counts > or =500/ml, CR of MTCT were 0.091 in the zidovudine and 0.220 in the placebo group, a significant 59% reduction. CONCLUSION: A maternal short-course zidovudine regimen reduces MTCT of HIV-1 at age 24 months, despite prolonged breastfeeding. However, efficacy was observed only among women with CD4 cell counts > or =500/ml. New interventions should be considered to prevent MTCT, especially for African women with advanced HIV-1 immunodeficiency.     

HIV-1 and herpes simplex virus type-2 genital shedding among co-infected women using self-collected swabs in Chiang Rai, Thailand

We analysed 528 genital self-collected swabs (SCS) from 67 HIV-1 and herpes simplex virus type-2 (HSV-2) co-infected women collected during the placebo month of a randomized crossover clinical trial of suppressive acyclovir in Chiang Rai, Thailand. In this first longitudinal study of HIV-1 and HSV-2 co-infected women using genital SCS specimens, we found frequent mucosal HIV-1 shedding. Overall, 372 (70%) swabs had detectable HIV-1 RNA with median HIV-1 viral load of 2.61 log(10) copies/swab. We found no statistically significant association between detectable HIV-1 RNA and HSV-2 DNA in the same SCS specimen (adjusted odds ratio [aOR] 1.40; 95% confidence intervals [CI], 0.78-2.60, P = 0.25). Only baseline HIV-1 plasma viral load was independently associated with genital HIV-1 RNA shedding (aOR, 7.6; 95% CI, 3.3-17.2, P < 0.0001). SCS may be useful for future HIV-1 and HSV-2 studies because this method allows for frequent genital sampling, and inclusion of genital sites other than the cervix.