Background Highly active antiretroviral treatment (HAART) has only been recently recommended for HIV-infected pregnant women requiring treatment for their own health in resource-limited settings. However, there are few documented experiences from African countries. We evaluated the short-term (4 wk) and long-term (12 mo) effectiveness of a two-tiered strategy of prevention of mother-to-child transmission of HIV (PMTCT) in Africa: women meeting the eligibility criteria of the World Health Organization (WHO) received HAART, and women with less advanced HIV disease received short-course antiretroviral (scARV) PMTCT regimens. Methods and Findings The MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women enrolled in Abidjan, Côte d'Ivoire received either HAART for their own health or short-course antiretroviral (scARV) PMTCT regimens according to their clinical and immunological status. Plasma HIV-RNA viral load (VL) was measured to diagnose peripartum infection when infants were 4 wk of age, and HIV final status was documented either by rapid antibody testing when infants were aged ≥ 12 mo or by plasma VL earlier. The Kaplan-Meier method was used to estimate the rate of HIV transmission and HIV-free survival. Between August 2003 and June 2005, 107 women began HAART at a median of 30 wk of gestation, 102 of them with zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) and they continued treatment postpartum; 143 other women received scARV for PMTCT, 103 of them with sc(ZDV+3TC) with single-dose NVP during labour. Most (75%) of the infants were breast-fed for a median of 5 mo. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%–4.2%) and the cumulative rate at 12 mo was 5.7% (95% CI 2.5%–9.0%). The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%–7.0%) at age week 4 wk and 11.7% (95% CI 7.5%–15.9%) at 12 mo. Conclusions This two-tiered strategy appears to be safe and highly effective for short- and long-term PMTCT in resource-constrained settings. These results indicate a further benefit of access to HAART for pregnant women who need treatment for their own health.
Abstract Background Transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding may involve both cell-free and cell-associated virus. This latter viral reservoir remains, however, to be fully explored. CD4 + T cell-associated virus production in breast milk was therefore investigated. Methods The ex vivo spontaneous production of HIV-1 antigen and HIV-1 RNA by CD4 + T cells was measured in paired blood and breast milk samples from 15 HIV-1 infected women treated or not with antiretroviral drugs. Spontaneous antigen secreting cells (HIV-1-AgSCs) from breast milk and blood were enumerated by an ELISpot assay, and cell-associated HIV-1 RNA was quantified by real-time PCR in supernatants of CD4 + T cells cultured for 18 hours without addition of polyclonal activators. Results Among the CD4 + T cells present in breast milk, memory cells expressing high levels of cell-surface activation markers were predominant. Spontaneous HIV-1-AgSCs were detected and enumerated in the breast milk of all 15 women, with a median number of 13.0 and 9.5 HIV-1- AgSCs/106 CD4 + T cells in aviremic (n = 7) and viremic (n = 8) women, respectively. Cell- associated HIV-1 RNA was detected in cell-free supernatants from 4/7 aviremic and 5/8 viremic individuals at median levels of 190 and 245 copies/ml, respectively. Conclusions Activated CD4 + T cells producing HIV-1 are detected in the breast milk of untreated individuals as well as those receiving highly active antiretroviral therapy. This finding strongly suggests that HIV-1 replication occurs in latently infected CD4 + T cells that, upon spontaneous activation, revert to productively infected cells. These cells might be responsible for a residual breast milk transmission despite maternal highly active antiretroviral therapy.
ABSTRACT Our objective was to study didanosine pharmacokinetics in children after the administration of tablets, the only formulation available in Burkina Faso for which data are missing, and to establish relationships between doses, plasma drug concentrations, and treatment effects (efficacy/toxicity). Didanosine concentrations were measured for 40 children after 2 weeks and for 9 children after 2 to 5 months of treatment with a didanosine-lamivudine-efavirenz combination. A population pharmacokinetic model was developed with NONMEM. The link between the maximal concentration of the drug in plasma ( C max ), the area under the concentration-time curve (AUC), and the decrease in human immunodeficiency virus (HIV) type 1 RNA levels after 12 months of treatment was evaluated. The threshold AUC that improved efficacy was determined by the use of a Wilcoxon test for HIV RNA, and an optimized dosing schedule was simulated. Didanosine pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. The apparent clearance and volume of distribution were higher for tablets, probably due to a lower bioavailability with tablets than with pediatric powder. The decrease in the viral load after 12 months of treatment was significantly correlated with the didanosine AUC and C max ( P ≤ 0.02) during the first weeks of treatment. An AUC of >0.60 mg/liter·h was significantly linked to a greater decrease in the viral load (a decrease of 3 log 10 versus 2.4 log 10 copies/ml; P = 0.03) than that with a lower AUC. A didanosine dose of 360 mg/m 2 administered as tablets should be a more appropriate dose than 240 mg/m 2 to improve efficacy for these children. However, data on adverse events with this dosage are missing.
The frequency of transmitted HIV drug resistance (HIVDR) was evaluated in the context of rapid scale-up of antiretroviral treatment in Thailand, Vietnam, Burkina Faso, Côte d'Ivoire, and Senegal by using an adaptation of the WHO generic protocol of the HIV Drug Resistance Threshold Survey (HIVDR-TS) for sample collection and classification. Resistance-associated mutations were interpreted using the 2009 WHO list for epidemiological surveys. We included 266 subjects from the five study sites. Of the 266 RT and PR sequences analyzed, two from Vietnam harbored virus with major drug resistance mutations (G190A in RT for one individual and M46I in PR for the second individual). Phylogenetic analysis revealed that CRF01_AE predominates (>90%) in Thailand and Vietnam. CRF02 (>65%) cocirculates with other HIV-1 variants in Senegal and Côte d'Ivoire. The prevalence of HIVDRM is scored as low (≤5%) in all the five sites for the three drug classes analyzed. A continuous population survey for HIVDRM will provide a rational basis for maintaining or changing the current first line regimen in these countries.
An age- and gender-specific distribution characterizes human T-cell lymphotrophic virus type-I (HTLV-I) seropositivity in Guadeloupe (French West Indies). Further epidemiological studies are required to identify other possible risk factors associated with this retroviral infection.A nested case-control study was conducted between 1997 and 1999 among blood donors. A total of 102 HTLV-I-positive subjects were matched (at a ratio of 1 : 3) by gender, age (+/-5 years) and donor status (new or regular) to 306 HTLV-I-negative controls. Information was obtained through a questionnaire assessing both environmental and behavioural variables.Factors independently associated with HTLV-I infection included a low level of education [odds ratio (OR) 6.61, confidence interval (CI) 2.89-15.15], black ethnicity (OR 3.28, CI 1.01-10.65), two or more sex partners in the previous 3 years (OR 2.43, CI 1.16-5.10), early age at first sexual intercourse (0.84 risk reduction per additional year, CI 0.76-0.93), a history of sexually transmitted diseases (OR 2.29, CI 1.0-5.34) and positive Chlamydia serology (OR 1.95, CI 1.03-3.68).These data provide a wide spectrum of features associated with HTLV-I seropositivity, especially sexual risk factors. It strongly suggests that heterosexual intercourse is an important route of HTLV-I transmission in Guadeloupe, even among low-risk populations such as blood donors.
The routes of transmission of human herpes virus 8 (HHV-8) remain unclear. In particular, HHV-8 transmission by blood components and organ transplantation is still debated and raises public health issues. The objective of this study was to determine the prevalence of anti-HHV-8 in selected populations of persons or patients with or without risk factors for the transmission of viral infections, in order to determine the routes of HHV-8 transmission.A total of 1431 persons or patients at low or high risk of sexually, blood-, or graft-transmitted viral infections were tested by means of a standardized immunofluorescence serologic assay detecting anti-HHV-8.The persons or patients could be classified into three distinct groups according to anti-HHV-8 prevalence: a low prevalence group (0.0% to 5.0%), including healthy blood donors, healthy pregnant women, multiply transfused patients with thalassemia major, and IV drug users; an intermediate prevalence group (5.0% to 20.0%), including organ donors, kidney transplant recipients, and multiply transfused patients with sickle cell disease; a high prevalence group (>20.0%), including HIV-negative persons at high risk of sexually-transmitted viral infections, and HIV-infected homosexual men and heterosexuals.The sexual route appears to be the main route of HHV-8 transmission; bloodborne transmission of HHV-8, if it exists, is rare. In contrast, organ transplantation recipients might be exposed to HHV-8 transmission by the transplanted organ, which raises the issue of systematic screening of organ donors.
Objectives: To describe acute retroviral syndrome and associated primary viraemia in African children infected with HIV-1 through breastfeeding. Design: Matched case–control study performed retrospectively within the ANRS 049 DITRAME project conducted in 1995–1998 in Abidjan, Côte d'Ivoire. Methods: Cases were children infected by HIV-1 postnatally through breastfeeding. All were HIV-1 negative by DNA PCR at least 45 days of age, but positive on a subsequent sample. This period was considered as surrounding the estimated date of postnatal contamination. Signs/symptoms occurring within this period were recorded in cases and compared with those occuring during the same time period in uninfected breastfed children (controls). For cases, plasma specimens were tested for HIV-1 plasma RNA using the branched DNA assay. Results: Of 22 infants infected postnatally (median age at first positive sample, 185 days; range, 87–373 days), 21 (95.5%) exhibited at least one clinical sign, compared with only 27 of the 44 (61.4%) uninfected children (P = 0.003). Three independent factors were associated with primary HIV-1 infection: mononucleosis-like syndrome [odds ratio (OR), 8.3; 95% confidence interval (CI), 1.4–47.8], dermatitis (OR, 6.0; CI, 1.1–31.9), and generalized lymphadenopathy (OR, 26.5; CI, 2.0–348.4). Among cases, initial median plasma HIV-1 RNA viral load was 5.92 log10 copies/ml; this declined to 4.96 log10 12 months after the first positive viral load. Conclusions: These results may be useful for the recognition of early paediatric cases of postnatal transmission in Africa and could enable targeting of those who should benefit from HIV RNA or DNA testing for primary HIV-1 infection and their subsequent care.
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