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Robert W. Coombs

Bio: Robert W. Coombs is an academic researcher from University of Washington. The author has contributed to research in topics: Viral load & Zidovudine. The author has an hindex of 70, co-authored 256 publications receiving 25267 citations. Previous affiliations of Robert W. Coombs include University of Rochester & University of Washington Medical Center.


Papers
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Journal ArticleDOI
TL;DR: In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds.
Abstract: Background and Methods Maternal-infant transmission is the primary means by which young children become infected with human immunodeficiency virus type 1 (HIV). We conducted a randomized, double-blind, placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission. HIV-infected pregnant women (14 to 34 weeks' gestation) with CD4+ T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled. The zidovudine regimen included antepartum zidovudine (100 mg orally five times daily), intrapartum zidovudine (2 mg per kilogram of body weight given intravenously over a one-hour period, then 1 mg per kilogram per hour until delivery), and zidovudine for the newborn (2 mg per kilogram orally every six hours for six weeks). Infants with at least one positive HIV culture of peripheral-blood mononuclear cells were classified as HIV-infected. Results From April 1991 through Decemb...

3,604 citations

Journal ArticleDOI
TL;DR: Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women, and both study medications significantly reduced the HIV- 1 incidence among both men andWomen.
Abstract: Background Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. Methods We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1–serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1–seronegative partner in each couple was randomly assigned to one of three study regimens — once-daily tenofovir (TDF), combination tenofovir–emtricitabine (TDF–FTC), or matching placebo — and followed monthly for up to 36 months. At enrollment, the HIV-1–seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. Results We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF–FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1–seronegative partner was male. Among HIV-1–seropositive par...

2,752 citations

Journal ArticleDOI
TL;DR: It was shown that AZT decreased the maternal-infant transmission of HIV and helped decrease infant mortality due to the viral infection.
Abstract: In 1994, Edward M. Connor and colleagues published \"Reduction of Maternal-Infant Transmission of Human Immunodeficiency Virus Type 1 with Zidovudine Treatment.\" Their study summarized how to reduce the transfer of human immunodeficiency virus, or HIV, from pregnant women to their fetuses with Zidovudine, otherwise known as AZT. HIV is a virus that weakens the immune system by destroying white blood cells, a part of the body ́s immune system. Fifteen to forty percent of infants born to HIVpositive mothers become infected during fetal development, labor and delivery, or breast-feeding. From April 1991 to December 1993, Connor and his colleagues researched HIV-positive pregnant women who took AZT, a drug that treats but does not cure an HIV infection. In their article, Conner and colleagues showed that AZT decreased the maternal-infant transmission of HIV and helped decrease infant mortality due to the viral infection.

1,964 citations

Journal ArticleDOI
TL;DR: This drug combination reduced HIV-1 replication, increased CD4+ cell counts, and decreased levels of activation markers in serum more than did treatment with zidovudine and either saquinavir or zalcitabine.
Abstract: Background In patients with human immunodeficiency virus (HIV) infection, combined treatment with several agents may increase the effectiveness of antiviral therapy. We studied the safety and efficacy of saquinavir, an HIV-protease inhibitor, given with one or two nucleoside antiretroviral agents, as compared with the safety and efficacy of a combination of two nucleosides alone. Methods In this double-blind trial, patients with HIV infection were randomly assigned to receive either saquinavir (1800 mg per day) plus both zidovudine (600 mg per day) and zalcitabine (2.25 mg per day) or zidovudine plus either saquinavir or zalcitabine. The 302 patients enrolled had CD4+ counts of 50 to 300 cells per cubic millimeter and had previously received zidovudine for a median of 27 months. The study lasted 24 weeks, with an optional double-blind extension period of an additional 12 to 32 weeks. Results Ninety-six percent of the patients completed the 24-week study. In all three treatment groups, CD4+ cell counts ros...

738 citations

Journal ArticleDOI
TL;DR: A placebo-controlled trial has shown that treatment with zidovudine reduces the rate at which human immunodeficiency virus type 1 (HIV-1) is transmitted from mother to infant as discussed by the authors.
Abstract: Background and Methods A placebo-controlled trial has shown that treatment with zidovudine reduces the rate at which human immunodeficiency virus type 1 (HIV-1) is transmitted from mother to infant. We present data from that trial showing the number of infected infants at 18 months of age and the relation between the maternal viral load, the risk of HIV-1 transmission, and the efficacy of zidovudine treatment. Viral cultures were obtained, and HIV-1 RNA was measured by two assays in samples of maternal blood obtained at study entry and at delivery. Results In 402 mother–infant pairs, the rate of transmission of HIV-1 was 7.6 percent (95 percent confidence interval, 4.3 to 12.3 percent) with zidovudine treatment and 22.6 percent (95 percent confidence interval, 17.0 to 29.0 percent) with placebo (P<0.001). In the placebo group, a large viral burden at entry or delivery or a positive culture was associated with an increased risk of transmission (the transmission rate was greater than 40 percent in the highe...

728 citations


Cited by
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Journal ArticleDOI
TL;DR: The recent declines in morbidity and mortality due to AIDS are attributable to the use of more intensive antiretroviral therapies.
Abstract: Background and Methods National surveillance data show recent, marked reductions in morbidity and mortality associated with the acquired immunodeficiency syndrome (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of whom had at least one CD4+ count below 100 cells per cubic millimeter, who were seen at nine clinics specializing in the treatment of human immunodeficiency virus (HIV) infection in eight U.S. cities from January 1994 through June 1997. Results Mortality among the patients declined from 29.4 per 100 person-years in 1995 to 8.8 per 100 person-years in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in t...

9,116 citations

Journal ArticleDOI
TL;DR: In this article, Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples.
Abstract: Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we...

5,871 citations

Journal ArticleDOI
TL;DR: These Guidelines were developed by the Panel* on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services and the Henry J. Kaiser Family Foundation.
Abstract: SUMMARY The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced extraordinary complexity into the treatment of HIV-infected persons. In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for the clinical management of HIV-infected adults and adolescents. This report recommends that care should be supervised by an expert, and makes recommendations for laboratory monitoring including plasma HIV RNA, CD4 cell counts and HIV drug resistance testing. The report also provides guidelines for antiretroviral therapy, including when to start treatment, what drugs to initiate, when to change therapy, and therapeutic options when changing therapy. Special considerations are provided for adolescents and pregnant women. As with treatment of other chronic conditions, therapeutic decisions require a mutual understanding between the patient and the health care provider regarding the benefits and risks of treatment. Antiretroviral regimens are complex, have major side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance due to non-adherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic

4,321 citations

Journal ArticleDOI
TL;DR: The exciting evidence generated by this paper – that antiretroviral treatment of HIV-1 infection definitively reduces the risk of onward transmission of the virus by 96% – was rightly dubbed Science magazine's ‘Breakthrough of the Year’ in 2011.
Abstract: MS Cohen, YQ Chen, M McCauley N Engl J Med 2011 365:493–505. The exciting evidence generated by this paper – that antiretroviral treatment of HIV-1 infection definitively reduces the risk of onward transmission of the virus by 96% – was rightly dubbed Science magazine's ‘Breakthrough of the Year’ in 2011.1 ,2 It has long been known that the probability of sexual transmission of HIV is strongly correlated with concentrations of HIV in blood and genital fluids.3 ,4 Effective antiretroviral therapy (ART) produces prolonged and sustained suppression of HIV replication in these compartments, reducing the amount of free virus.5 ,6 Thus, there has long been a …

4,259 citations

Journal ArticleDOI
TL;DR: Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects and Detectable blood levels strongly correlated with the prophylactic effect.
Abstract: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at en rollment, and 100 became infected during follow-up (36 in the FTC–TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P = 0.005). In the FTC–TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC–TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P = 0.57). Conclusions Oral FTC–TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foun dation; ClinicalTrials.gov number, NCT00458393.)

4,247 citations