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This double-blind, randomized trial in Botswana compared two highly active antiretroviral regimens in HIV-1−infected pregnant women (CD4+ count, ≥200) from pregnancy through 6 months post partum (when breast-feeding ceased). Both regimens were highly effective in suppressing the maternal HIV-1 viral load as well as mother-to-child transmission, with an overall transmission rate of 1.1%. Highly active antiretroviral therapy (HAART) used to prevent in utero and intrapartum mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) is among the most successful public health interventions of the HIV era. 1 , 2 However, the use of HAART in mothers to prevent mother-to-child transmission through breast-feeding in areas of the world where replacement feeding is neither safe nor feasible remains an unproven strategy. 1 , 3 We compared different HAART regimens used in pregnancy and during breast-feeding to determine whether the regimens differ with respect to virologic suppression during pregnancy and breast-feeding, pregnancy outcomes, and toxic effects in mothers and infants. . . .

This study analyzed the response to nevirapine-based antiretroviral treatment among 218 HIV-infected women in Botswana who had previously received either a single dose of nevirapine or placebo at the time of labor. After the single dose of nevirapine, 18.4% of recipients had treatment failure, as compared with only 5.0% who received placebo. However, the risk of virologic failure did not seem to be increased when antiretroviral treatment was initiated 6 months or more, as compared with less than 6 months, after the peripartum dose of nevirapine. This study analyzed the response to nevirapine-based antiretroviral treatment among 218 HIV-infected women in Botswana who had previously received either a single dose of nevirapine or placebo at the time of labor. Nevirapine remains central to the prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) and to combination antiretroviral treatment throughout much of the developing world. 1 , 2 Nevirapine administered as one dose to the mother and one to the newborn reduces mother-to-child transmission of HIV-1 by 41 to 47%, 3 , 4 and well over 875,000 women and infants have received a single dose of nevirapine. 5 A single dose of nevirapine is the cornerstone of the regimen recommended by the World Health Organization (WHO) to prevent mother-to-child transmission among women without access to antiretroviral treatment and among those not meeting treatment . . .

BackgroundThe magnitude of infant antiretroviral (ARV) exposure from breast milk is unknown MethodsWe measured concentrations of nevirapine, lamivudine, and zidovudine in serum and whole breast milk from human immunodeficiency virus type 1 (HIV-1)–infected women in Botswana receiving ARV treatment and serum from their uninfected, breast-feeding infants ResultsTwenty mother-infant pairs were enrolled. Maternal serum concentrations of nevirapine were high (median, 9534 ng/mL at a median of 4 h after nevirapine ingestion). Median breast-milk concentrations of nevirapine, lamivudine, and zidovudine were 0.67, 3.34, and 3.21 times, respectively, those in maternal serum. The median infant serum concentration of nevirapine was 971 ng/mL, at least 40 times the 50% inhibitory concentration and similar to peak concentrations after a single 2-mg/kg dose of nevirapine. The median infant serum concentration of lamivudine was 28 ng/mL, and the median infant serum concentration of zidovudine was 123 ng/mL, but infants were also receiving zidovudine prophylaxis ConclusionsHIV-1 inhibitory concentrations of nevirapine are achieved in breast-feeding infants of mothers receiving these ARVs, exposing infants to the potential for beneficial and adverse effects of nevirapine ingestion. Further study is needed to understand the impact of maternal ARV treatment on breast-feeding HIV-1 transmission, infant toxicity, and HIV-1 resistance mutations among infected infants

BackgroundThe ability of highly active antiretroviral therapy (HAART) to reduce human immunodeficiency virus type 1 (HIV-1) RNA and DNA in breast milk has not been described MethodsWe compared breast-milk HIV-1 RNA and DNA loads of women in Botswana who received HAART (nevirapine, lamivudine, and zidovudine) and women who did not receive HAART ResultsWomen in the HAART group received treatment for a median of 98 days (range, 67–222 days) at the time of breast-milk sampling; 23 (88%) of 26 had whole breast-milk HIV-1 RNA loads <50 copies/mL, compared with 9 (36%) of 25 women who did not receive HAART (P=.0001). This finding remained significant in a multivariate logistic-regression model (P=.0006). The whole-milk HIV-1 DNA load was unaffected by HAART. Of women who received HAART, 13 (50%) of 26 had HIV-1 DNA loads <10 copies/106 cells, compared with 15 (65%) of 23 who did not receive HAART (P=.39) ConclusionsHAART suppressed cell-free HIV-1 RNA in breast milk and may therefore reduce mother-to-child transmission (MTCT) of HIV-1 via breast-feeding. However, HAART initiated during pregnancy or early after delivery had no apparent effect on cell-associated HIV-1 DNA loads in breast milk. Clinical trials to determine MTCT among breast-feeding women receiving HAART are needed

Background: Male circumcision is known to reduce the risk of acquiring HIV, but few studies have been performed to assess its acceptability among either children or adults in sub-Saharan Africa. Methods: We conducted a cross sectional survey in nine geographically representative locations in Botswana to determine the acceptability of male circumcision in the country, as well as the preferred age and setting for male circumcision. Interviews were conducted using standardised questionnaires both before and after an informational session outlining the risks and benefits of male circumcision. Results: Among 605 people surveyed, the median age was 29 years (range 18–74 years), 52% were male, and >15 ethnicities were represented. Before the informational session, 408 (68%) responded that they would definitely or probably circumcise a male child if circumcision was offered free of charge in a hospital setting; this number increased to 542 (89%) after the informational session. Among 238 uncircumcised men, 145 (61%) stated that they would definitely or probably get circumcised themselves if it were offered free of charge in a hospital setting; this increased to 192 (81%) after the informational session. In a multivariate analysis of all participants, people with children were more likely to favour circumcision than people without children (adjusted odds ratio 1.8, 95% CI 1.0 to 3.4). Most participants (55%) felt that the ideal age for circumcision is before 6 years, and 90% of participants felt that circumcision should be performed in the hospital setting. Conclusions: Male circumcision appears to be highly acceptable in Botswana. The option for safe circumcision should be made available to parents in Botswana for their male children. Circumcision might also be an acceptable option for adults and adolescents, if its efficacy as an HIV prevention strategy among sexually active people is supported by clinical trials.

Because of the similar virological properties of HIV types 1 and 2, HIV-2 was assumed to be as infectious and capable of inducing AIDS as HIV-1. Seroepidemiological studies have shown significant rates of HIV-2 infection in West Africa, and surveys from other regions of the world indicate that the spread of HIV-2 infection continues. However the pathogenic potential of HIV-2 is considered to be lower than that of HIV-1. It is therefore important to understand the transmission properties of HIV-2 and its contribution to the AIDS pandemic. Since 1985,we have prospectively studied 1452 registered female prostitutes in Dakar, Senegal, with sequential evaluation of their antibody status to HIV-1 and HIV-2. During the study the overall incidence of HIV-1 and HIV-2 was the same (1·11 per 100 person-years of observation [pyo]). However, the annual incidence of HIV-1 increased substantially: there was a 1·4-fold increased risk per year and thus a 12-fold increase in risk over the entire study period. The incidence of HIV-2 remained stable, despite higher HIV-2 prevalence. In our population the heterosexual spread of HIV-2 is significantly slower than that of HIV-1, which strongly suggests differences in the viruses' infectivity potential.

Perinatal transmission of human immunodeficiency virus (HIV)-1 represents a major problem in many regions of the world, especially Southern Africa. With the exception of viral and proviral load, the role for maternal cofactors in perinatal transmission outcome is largely unknown. In this study, an assessment was made of peripheral blood mononuclear cells (PBMC) gene-expression profiles to better understand transcriptional changes associated with HIV-1 infection and perinatal transmission among young adult mothers with infants in Botswana. Peripheral blood mononuclear cells specimens were used from 25 HIV+ drug naive and 20 HIV− healthy mothers, similar in age and location, collected in 1999–2000 and 2003, and processed with the exact same methods, as previously described. Expression profiling of 22 277 microarray gene probes implicated a broad initiation of innate response gene-sets, including toll-like receptor, interferon-stimulated and antiviral RNA response pathways in association with maternal HIV-1 infection. Maternal transmission status was further associated with host genes that influence RNA processing and splicing patterns. In addition to real-time polymerase chain reaction validation of specific genes, enriched category validation of PBMC profiles was conducted using two independent data sets for either HIV-1 infection or an unrelated RNA virus, severe acute respiratory virus infection. HIV-1 pathogen-specific host profiles should prove a useful tool in infection and transmission intervention efforts worldwide.

This cluster randomised trial in KwaZulu-Natal South Africa, evaluated the implementation of a Feeding Buddies (FB) programme to improve exclusive breastfeeding (EBF) amongst human immunodeficiency virus infected mothers. Eight clinics were randomly allocated to intervention and control arms respectively. Pregnant women attending the prevention of mother-to-child transmission program and intending to EBF were enrolled: control (n = 326), intervention (n = 299). Intervention mothers selected FBs to support them and they were trained together (four sessions). Interviews of mothers occurred prenatally and at post-natal visits (day 3, weeks 6, 14 and 22). Breastfeeding results were analysed (Stata) as interval-censored time-to-event data, with up to four time intervals per mother. EBF rates at the final interview were similar for control and intervention groups: 44.68% (105/235) and 42.75% (109/255) respectively (p = 0.67). In Cox regression analysis better EBF rates were observed in mothers who received the appropriate training (p = 0.036), had a community care giver visit (p = 0.044), while controlling for other factors. Implementation realities reduced the potential effectiveness of the FBs.

Little is known about the ability of women to adhere to recommended feeding strategies to prevent mother-to-child HIV transmission (MTCT) from breast milk. We conducted a pilot study in rural Botswana to prevent MTCT from breast milk. Women were randomized to formula feed their infants or to exclusively breastfeed while providing prophylactic zidovudine. Women who chose to formula feed independently were also followed. Among those with > or = 3 postpartum visits, none of 31 women assigned to breastfeed did so exclusively for 5 months. Seven (22%) of 32 women in the formula arm definitely or probably breastfed by self-report or as witnessed in maternity, and evidence of breast milk on physical examination was present in 50% of women in > or = 2 visits beyond 1 month. Three (18%) of 17 women choosing formula definitely or probably breastfed, and breast milk was present on exam in 53%. We conclude that adherence to 5 months of exclusive breastfeeding did not occur, and that adherence to exclusive formula feeding was sub-optimal and potentially over reported. Breast examination may be a useful adjunct to self-report, but needs to be validated and standardized. Low adherence to infant feeding strategies that differ from local norms will reduce their effectiveness in preventing MTCT.