Allan W. Taylor

Male circumcision in the United States for the prevention of HIV infection and other adverse health outcomes: report from a CDC consultation.

In April 2007, the Centers for Disease Control and Prevention (CDC) held a two-day consultation with a broad spectrum of stakeholders to obtain input on the potential role of male circumcision (MC) in preventing transmission of human immunodeficiency virus (HIV) in the U.S. Working groups summarized data and discussed issues about the use of MC for prevention of HIV and other sexually transmitted infections among men who have sex with women, men who have sex with men (MSM), and newborn males. Consultants suggested that (1) sufficient evidence exists to propose that heterosexually active males be informed about the significant but partial efficacy of MC in reducing risk for HIV acquisition and be provided with affordable access to voluntary, high-quality surgical and risk-reduction counseling services; (2) information about the potential health benefits and risks of MC should be presented to parents considering infant circumcision, and financial barriers to accessing MC should be removed; and (3) insufficient data exist about the impact (if any) of MC on HIV acquisition by MSM, and additional research is warranted. If MC is recommended as a public health method, information will be required on its acceptability and uptake. Especially critical will be efforts to understand how to develop effective, culturally appropriate public health messages to mitigate increases in sexual risk behavior among men, both those already circumcised and those who may elect MC to reduce their risk of acquiring HIV.

Correlates of Mother-to-Child Transmission of HIV in the United States and Puerto Rico

OBJECTIVE: The goal of this study was to examine associations between demographic, behavioral, and clinical variables and mother-to-child HIV transmission in 15 US jurisdictions for birth years 2005 through 2008. METHODS: The study used Enhanced Perinatal Surveillance system data for HIV-infected women who gave birth to live infants. Multivariable logistic regression was used to assess variables associated with mother-to-child transmission. RESULTS: Among 8054 births, 179 infants (2.2%) were diagnosed with HIV infection. Half of the births had at least 1 missed prevention opportunity: 74.3% of infected infants, 52.1% of uninfected infants. Among 7757 mother–infant pairs with sufficient data for analysis, the odds of having an HIV-infected infant were higher for women who received late testing or no prenatal antiretroviral medications (odds ratio: 2.5 [95% confidence interval (CI): 1.5–4.0] and 3.5 [95% CI: 2.0–6.4], respectively). The odds for mothers who breastfed were 4.6 times (95% CI: 2.2–9.8) the odds for those who did not breastfeed. The adjusted odds for women with CD4 counts <200 cells per microliter were 2.4 times (95% CI: 1.4–4.2) those for women with CD4 counts ≥500 cells per microliter. The odds for women who abused substances were twice (95% CI: 1.4–2.9) those for women who did not. CONCLUSIONS: The odds of having an HIV-infected infant were higher among HIV-infected women who were tested late, had no antiretroviral medications, abused substances, breastfed, or had lower CD4 cell counts. Increases in earlier HIV diagnosis, substance abuse treatment, avoidance of breastfeeding, and use of prenatal antiretroviral medications are critical in eliminating perinatal HIV infections in the United States.

Estimated number of infants born to HIV-infected women in the United States and five dependent areas, 2006.

Objective:Although perinatal HIV infections are declining in the United States, there is no single source of nationally representative data available to estimate the number of infants born to HIV-infected women in the United States and its dependencies. This study determines the total number of births to HIV-positive women in the United States and 5 dependent areas in 2006. Study Design:Diagnosed stage 1 or 2 HIV disease in the United States were based on reported data from 39 areas that conducted confidential name-based HIV case reporting and stage 3 HIV from all areas in the United States. A zero-inflated Poisson model was used to estimate the number of women aged 13-44 years living with diagnosed stage 1 or 2 HIV disease in the United States. The number of undiagnosed HIV-infected women (stage 1 or 2) of childbearing age was estimated from the number of reported Stage 3 HIV (ie, AIDS) cases using a back-calculation method. Results:An estimated 115,200 women aged 13-44 years were living with stage 1 or 2 HIV disease in 2006. A total of 56,200 women were living with diagnosed stage 3 disease. The estimated number of births to all women living with HIV disease (diagnosed or undiagnosed) was 8700 [95% Confidence Interval (CI): 8400 to 8800] in 2006. Conclusions:The number of infants born to HIV-infected women in 2006 was approximately 30% greater than the number of such births (6075-6422) in 2000. This increase highlights the need to continue and strengthen efforts to prevent perinatal HIV transmission in the United States.

A Framework for Elimination of Perinatal Transmission of HIV in the United States

The availability of effective interventions to prevent mother-to-child HIV transmission and the significant reduction in the number of HIV-infected infants in the United States have led to the concept that elimination of mother-to-child HIV transmission (EMCT) is possible. Goals for elimination are presented. We also present a framework by which elimination efforts can be coordinated, beginning with comprehensive reproductive health care (including HIV testing) and real-time case-finding of pregnancies in HIV-infected women, and conducted through the following: facilitation of comprehensive clinical care and social services for women and infants; case review and community action; allowing continuous quality research in prevention and long-term follow-up of HIV-exposed infants; and thorough data reporting for HIV surveillance and EMCT evaluation. It is emphasized that EMCT will not be a one-time accomplishment but, rather, will require sustained effort as long as there are new HIV infections in women of childbearing age.

Male Circumcision for Prevention of HIV Transmission: What the New Data Mean for HIV Prevention in the United States

Recent clinical trials in Africa found that male circumcision reduces the risk of acquiring HIV from heterosexual sex--what are the implications of these studies for the United States?

Effects of Cessation of Breastfeeding in HIV-1–Exposed, Uninfected Children in Malawi

BACKGROUND We assessed morbidity rates during short intervals that accompanied weaning and cumulative mortality among HIV-exposed, uninfected infants enrolled in the postexposure prophylaxis of infants in Malawi (PEPI-Malawi) trial. METHODS Women were counseled to stop breastfeeding (BF) by 6 months in the PEPI-Malawi trial. HIV-uninfected infants were included in this analysis starting at age 6 months. Breastfeeding and morbidity (illness and/or hospital admission and malnutrition [weight-for-age Z-score, ≤2]) were assessed during age intervals of 6-9, 9-12, and 12-15 months. BF was defined as any BF at the start and end of the interval and no breastfeeding (NBF) was defined as NBF at any time during the interval. The association of NBF with morbidity at each mutually exclusive interval was assessed using Poisson regression models controlling for other factors. Cumulative mortality among infants aged 6-15 months with BF and NBF was assessed using an extended Kaplan-Meier method. RESULTS At age 6 months, 1761 HIV-uninfected infants were included in the study. The adjusted rate ratios for illnesses and/or hospital admission for NBF, compared with BF, was 1.7 (P < .0001) at 6-9 months, 1.66 (P = .0001) at 9-12 months, and 1.75 (P = .0008) at 12-15 months. The rates of morbidity were consistently higher among NBF infants during each age interval, compared with BF infants. The 15 months cumulative mortality among BF and NBF children was 3.5% and 6.4% (P = .03), respectively. CONCLUSIONS Cessation of BF is associated with acute morbidity events and cumulative mortality. Prolonged BF should be encouraged, in addition to close monitoring of infant health and provision of support services.

Botswana's Tebelopele voluntary HIV counseling and testing network: use and client risk factors for HIV infection, 2000-2004.

Background:HIV services, including voluntary counseling and testing (VCT) and antiretroviral (ARV) therapy, expanded rapidly in Botswana from 2000 through 2004. Methods:Client data from Botswanas Tebelopele VCT network were analyzed to describe clients, factors associated with HIV infection, and trends in VCT use. Results:Tebelopele provided free, anonymous, same-day HIV tests for 117,234 clients from 2000 through 2004. Before ARV therapy was available, 8.3% of clients sought a test because of illness, and 26.3% were HIV-positive. After ARV therapy became available, 20.1% of clients sought a test because of illness, and 38.8% were HIV-positive. Most VCT clients (82.7%) were unmarried; 89.8% reported no or 1 sexual partner in the last 3 months; and 50.2% of unmarried clients reported always using condoms in the last 3 months. In multivariate analysis, higher educational level, marriage, and always using condoms were associated with a lower risk of HIV. Having only 1 recent sexual partner was associated with less condom use and a higher risk of being HIV-positive for men. Conclusions:VCT has been well accepted in Botswana. Analysis of this data set supports efforts to promote 100% condom use and to emphasize that partner reduction must be combined with condom use and HIV testing to protect against HIV.

Postexposure prophylaxis of breastfeeding HIV-exposed infants with antiretroviral drugs to age 14 weeks: updated efficacy results of the PEPI-Malawi trial.

Background:This analysis updates and extends efficacy estimates of the PEPI-Malawi trial through age 24 months at study completion in September 2009. Methods:Infants of breastfeeding HIV-infected women were randomized at birth to the following: (1) single-dose nevirapine (NVP) + 1-week zidovudine (ZDV) (control); (2) control + extended daily NVP (ExtNVP) through 14 weeks; (3) control + extended daily NVP + ZDV (ExtNVP/ZDV) through 14 weeks. We estimated rates of HIV infection, death and HIV infection, or death using Kaplan-Meier analysis. Results:This analysis includes 3126 infants uninfected at birth as follows: 1004 control, 1071 ExtNVP, and 1051 ExtNVP/ZDV. By 9 months, HIV infection rates were 5.0% in ExtNVP, 6.0% in ExtNVP/ZDV, and 11.1% in control (P < 0.001 comparing extended regimens with control). At age 24 months, HIV infection rates had risen to ∼11% in the extended arms compared with 15.6% in the controls (P < 0.05). The rates of HIV infection or death were also significantly lower in extended arms. There were no differences in severe adverse events with the exception of higher possibly related events in the ExtNVP/ZDV arm. Conclusions:Daily infant antiretroviral prophylaxis reduces postnatal HIV infection by ∼70% during the period of prophylaxis. But continued HIV transmission after prophylaxis stops suggests more prolonged infant prophylaxis is needed.

Association of recent HIV infection and in-utero HIV-1 transmission.

Objective:We previously developed a multiassay algorithm (MAA) to identify recent HIV infection that includes the BED-capture enzyme immunoassay, an avidity assay based on the Genetic Systems HIV-1/HIV-2 + O enzyme immunoassay, CD4 cell count, and HIV viral load. We used this MAA to evaluate the association between recent maternal HIV infection and in-utero transmission of HIV. Methods:Plasma samples were collected at delivery from 2561 HIV-infected women in the postexposure prophylaxis of infants-Malawi trial. The MAA described above was used to identify women with recent HIV infection. Logistic regression models assessed association between recent HIV infection and in-utero HIV transmission (defined as a positive infant HIV DNA test at birth). Results:Seventy-three women were identified as recently infected using the MAA. Those women were younger and had lower parity than women who were identified as not recently infected using the MAA (P < 0.0001 for age and parity). The frequency of in-utero HIV transmission was 17.8% among women identified as recently infected, compared with 6.7% among women identified as not recently infected (13/73 vs. 166/2488, P = 0.001). In a multivariate model, three factors were independently associated with in-utero HIV transmission: recent infection [adjusted odds ratio (AOR): 2.49, 95% confidence interval (CI): 1.30–4.78, P = 0.006], log10 HIV viral load at delivery (AOR: 2.01, 95% CI: 1.60–2.51, P < 0.0001), and younger age (per 10 year increase, AOR: 0.66, 95% CI: 0.43–0.93, P = 0.02). Conclusion:Results obtained using a MAA suggest that recent maternal HIV acquisition is strongly associated with in-utero HIV transmission, independent of HIV viral load at delivery.

Pooled Individual Data Analysis of 5 Randomized Trials of Infant Nevirapine Prophylaxis to Prevent Breast-Milk HIV-1 Transmission

BACKGROUND In resource-limited settings, mothers infected with human immunodeficiency virus type 1 (HIV-1) face a difficult choice: breastfeed their infants but risk transmitting HIV-1 or not breastfeed their infants and risk the infants dying of other infectious diseases or malnutrition. Recent results from observational studies and randomized clinical trials indicate daily administration of nevirapine to the infant can prevent breast-milk HIV-1 transmission. METHODS Data from 5396 mother-infant pairs who participated in 5 randomized trials where the infant was HIV-1 negative at birth were pooled to estimate the efficacy of infant nevirapine prophylaxis to prevent breast-milk HIV-1 transmission. Four daily regimens were compared: nevirapine for 6 weeks, 14 weeks, or 28 weeks, or nevirapine plus zidovudine for 14 weeks. RESULTS The estimated 28-week risk of HIV-1 transmission was 5.8% (95% confidence interval [CI], 4.3%-7.9%) for the 6-week nevirapine regimen, 3.7% (95% CI, 2.5%-5.4%) for the 14-week nevirapine regimen, 4.8% (95% CI, 3.5%-6.7%) for the 14-week nevirapine plus zidovudine regimen, and 1.8% (95% CI, 1.0%-3.1%) for the 28-week nevirapine regimen (log-rank test for trend, P < .001). Cox regression models with nevirapine as a time-varying covariate, stratified by trial site and adjusted for maternal CD4 cell count and infant birth weight, indicated that nevirapine reduces the rate of HIV-1 infection by 71% (95% CI, 58%-80%; P < .001) and reduces the rate of HIV infection or death by 58% (95% CI, 45%-69%; P < .001). CONCLUSIONS Extended prophylaxis with nevirapine or with nevirapine and zidovudine significantly reduces postnatal HIV-1 infection. Longer duration of prophylaxis results in a greater reduction in the risk of infection.