- Email: [email protected]
Early treatment of HIV-1 infection
CORRESPONDENCE 2
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Autran B, Garcelain G, Li TS, et al. Positive effects of combined antiretroviral therapy on CD4+ cell homeostasis and function in advanced HIV disease. Science 1997; 277: 112–16. Perelson AS, Essinger P, Cao Y, et al. Decay characteristic of HIV-infected compartments during combination therapy. Nature 1997; 387: 188–91. Finzi D, Hermankova M, Pierson T, et al. Identification of a reservoir for HIV-1 in patients on highly active therapy. Science 1997; 278: 1295–300. Levy JA, Surrogate marker in AIDS research. Is there truth in numbers? JAMA 1996; 376: 161–62.
Sir—Jay Levy’s remark1 of decreased CD8-cell antiviral response in patients on triple therapy is valuable. Preliminary data of research in progress at our centre on the immunological effects of HAART administered as postexposure prophylaxis in HIV-1negative health-care workers seems to support the fact that the immune system could be compromised by the drugs. Thus, we are concerned even about the treatment of primary infection. Rosemberg and colleagues2 showed that antiviral therapy given before seroconversion seems to protect the cellular immune response to HIV-1. However, data reported by Ho at the 12th World AIDS Conference showed that eradication is still a dream, at least with this present approach. In primary infection drugs should be administered for a still undefined period and, as Levy underlines, virus production after discontinuation of HAART is usually increased. Moreover, the immune response observed in long-term survivors controls replication of HIV-1 without the need for antiviral treatment and the mean time to progression in the rest of the HIV-1 infected population is 8–10 years. For these reasons, together with the question of “should we be treating HIV1 infection early?”, we provocatively ask, “should primary HIV-1 infection be treated?” Finally, we agree with Levy’s call for new efforts in the understanding of the immune control of HIV-1 infection, since being able to preserve or potentiate the immune response in the very early stages is the most promising approach. *Francesco Milazzo, Stefania Piconi, Giuliano Rizzardini 1st Department of Infectious Diseases and Allergy, Luigi Sacco Hospital, 20157 Milan, Italy 1
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Lewy JA. Caution: should we be treating HIV infection early? Lancet 1998; 352: 982–83. Rosemberg ES, Billingsley JM, Caliendo AM, et al. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 1997, 278: 1447–50.
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Author’s reply Sir—Your correspondents’ views underscore my comments on the administration of antiretrovirals to infected individuals before they may be required. I appreciate the understanding of Anthony Fauci and colleagues that flexibility is important in establishing thresholds of recommendation of treatments. The studies of Francesco Montella and Francesco Milazzo and their co-workers indicate what has been seen as well at our institution: that late treatment of HIV-1 infection can lead to good immune responses. I would, however, withhold judgment about treatment of acute infection. Therapeutic intervention at that early period may help the initial anti-HIV-1 response in the host. We await the results of studies in progress to evaluate this possibility. With respect to my Viewpoint, I would like to correct the calculation of the number of productively infected cells at 30 000 viral RNA copies per mL. The amount of viral RNA copies per mL should have read 30⫻103 and not 30⫻10 4. Thus, by these calculations, the number of infected cells releasing virus would actually be 45 000, again much fewer than the billions of cells infected. Jay A Levy University of California, San Francisco, CA 94143, USA
Breastfeeding and maternal employment Sir—I was surprised to read J H Knopf’s interpolation (Nov 21, p 1704)1 that the “real message” of my Oct 3 commentary2 is that the costs are too high for working mothers to breastfeed. In fact, the real messages were what I actually stated: (1) breastfeeding is beneficial for health reasons (and results in the health care costs savings to which Knopf alludes); (2) breastfeeding can be tremendously enjoyable for babies and mothers; (3) full-time employed mothers do not breastfeed for as long as part-time employed or unemployed mothers (but none of the groups studied breastfed for very long); and (4) society, and employers in particular, ought to make it easier for mothers to breastfeed for more extended periods, and there are some easy ways to accomplish that. I also suggest that, since I am a fulltime employed breastfeeding mother of a 20-month-old-baby, the idea that I
would “trivialise the benefits of breastfeeding”, allude to “putative costs to the breastfeeding working mother which authentic breastfeeding advocates would laughingly debunk”, or “force breastfeeding women into [a] recently vacated closet” is especially misguided. I had hoped not to be doctrinaire in advocating the value of breastfeeding, since this decision is complex and personal, and regret that my view was misinterpretable as being negative. Erica Frank Department of Community and Preventive Medicine, Emory University, Atlanta, GA 30303, USA (e-mail: [email protected]) 1 2
Knopf JH. Breastfeeding and maternal employment. Lancet 1998; 352: 1704. Frank E. Breastfeeding and maternal employment: two rights don’t make a wrong. Lancet 1998; 352: 1083–84.
Acute myocardial infarction associated with sildenafil Sir—J Feenstra and colleagues (Sept 19, p 957)1 describe a patient who had a myocardial infarction 30 min after taking his first dose of sildenafil. Apparently, the patient had no risk factors for ischaemic heart disease. How long after the myocardial infarction was blood sampled for measurement of serum lipids? Serum concentrations of cholesterol and its fractions are lower than the usual for a particular patient for up to 12 weeks after an acute myocardial infarction.2 In addition, serum LDL cholesterol was 3·4 mmol/L, which is the accepted limit2 for initiation of drug therapy in patients with coronary heart disease. Moreover, guidelines2 state that if LDL cholesterol at discharge in a patient who has had an acute myocardial infarction is equal to, or above 3·4 mmol/L, firm decisions about cholesterol-lowering therapy can be made, since the LDL concentration will probably be higher later, when the patient has not only recovered from the acute event but also re-established normal habits. Hence, Feenstra and colleagues’ patient probably had hypercholesterolaemia as a risk factor for ischaemic heart disease. In fact following the guidelines, drug treatment to lower cholesterol should be initiated at discharge. *L López-Lázaro, M García-Arenillas, A Portolés-Pérez, E Vargas-Castrillón, A Moreno-González Clinical Pharmacology Department, University Hospital San Carlos, 28040 Madrid, Spain (e-mail: “luislopez”[email protected])
THE LANCET • Vol 352 • December 12, 1998
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Autran B, Garcelain G, Li TS, et al. Positive effects of combined antiretroviral therapy on CD4+ cell homeostasis and function in advanced HIV disease. Science 1997; 277: 112–16. Perelson AS, Essinger P, Cao Y, et al. Decay characteristic of HIV-infected compartments during combination therapy. Nature 1997; 387: 188–91. Finzi D, Hermankova M, Pierson T, et al. Identification of a reservoir for HIV-1 in patients on highly active therapy. Science 1997; 278: 1295–300. Levy JA, Surrogate marker in AIDS research. Is there truth in numbers? JAMA 1996; 376: 161–62.
Sir—Jay Levy’s remark1 of decreased CD8-cell antiviral response in patients on triple therapy is valuable. Preliminary data of research in progress at our centre on the immunological effects of HAART administered as postexposure prophylaxis in HIV-1negative health-care workers seems to support the fact that the immune system could be compromised by the drugs. Thus, we are concerned even about the treatment of primary infection. Rosemberg and colleagues2 showed that antiviral therapy given before seroconversion seems to protect the cellular immune response to HIV-1. However, data reported by Ho at the 12th World AIDS Conference showed that eradication is still a dream, at least with this present approach. In primary infection drugs should be administered for a still undefined period and, as Levy underlines, virus production after discontinuation of HAART is usually increased. Moreover, the immune response observed in long-term survivors controls replication of HIV-1 without the need for antiviral treatment and the mean time to progression in the rest of the HIV-1 infected population is 8–10 years. For these reasons, together with the question of “should we be treating HIV1 infection early?”, we provocatively ask, “should primary HIV-1 infection be treated?” Finally, we agree with Levy’s call for new efforts in the understanding of the immune control of HIV-1 infection, since being able to preserve or potentiate the immune response in the very early stages is the most promising approach. *Francesco Milazzo, Stefania Piconi, Giuliano Rizzardini 1st Department of Infectious Diseases and Allergy, Luigi Sacco Hospital, 20157 Milan, Italy 1
2
Lewy JA. Caution: should we be treating HIV infection early? Lancet 1998; 352: 982–83. Rosemberg ES, Billingsley JM, Caliendo AM, et al. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 1997, 278: 1447–50.
1936
Author’s reply Sir—Your correspondents’ views underscore my comments on the administration of antiretrovirals to infected individuals before they may be required. I appreciate the understanding of Anthony Fauci and colleagues that flexibility is important in establishing thresholds of recommendation of treatments. The studies of Francesco Montella and Francesco Milazzo and their co-workers indicate what has been seen as well at our institution: that late treatment of HIV-1 infection can lead to good immune responses. I would, however, withhold judgment about treatment of acute infection. Therapeutic intervention at that early period may help the initial anti-HIV-1 response in the host. We await the results of studies in progress to evaluate this possibility. With respect to my Viewpoint, I would like to correct the calculation of the number of productively infected cells at 30 000 viral RNA copies per mL. The amount of viral RNA copies per mL should have read 30⫻103 and not 30⫻10 4. Thus, by these calculations, the number of infected cells releasing virus would actually be 45 000, again much fewer than the billions of cells infected. Jay A Levy University of California, San Francisco, CA 94143, USA
Breastfeeding and maternal employment Sir—I was surprised to read J H Knopf’s interpolation (Nov 21, p 1704)1 that the “real message” of my Oct 3 commentary2 is that the costs are too high for working mothers to breastfeed. In fact, the real messages were what I actually stated: (1) breastfeeding is beneficial for health reasons (and results in the health care costs savings to which Knopf alludes); (2) breastfeeding can be tremendously enjoyable for babies and mothers; (3) full-time employed mothers do not breastfeed for as long as part-time employed or unemployed mothers (but none of the groups studied breastfed for very long); and (4) society, and employers in particular, ought to make it easier for mothers to breastfeed for more extended periods, and there are some easy ways to accomplish that. I also suggest that, since I am a fulltime employed breastfeeding mother of a 20-month-old-baby, the idea that I
would “trivialise the benefits of breastfeeding”, allude to “putative costs to the breastfeeding working mother which authentic breastfeeding advocates would laughingly debunk”, or “force breastfeeding women into [a] recently vacated closet” is especially misguided. I had hoped not to be doctrinaire in advocating the value of breastfeeding, since this decision is complex and personal, and regret that my view was misinterpretable as being negative. Erica Frank Department of Community and Preventive Medicine, Emory University, Atlanta, GA 30303, USA (e-mail: [email protected]) 1 2
Knopf JH. Breastfeeding and maternal employment. Lancet 1998; 352: 1704. Frank E. Breastfeeding and maternal employment: two rights don’t make a wrong. Lancet 1998; 352: 1083–84.
Acute myocardial infarction associated with sildenafil Sir—J Feenstra and colleagues (Sept 19, p 957)1 describe a patient who had a myocardial infarction 30 min after taking his first dose of sildenafil. Apparently, the patient had no risk factors for ischaemic heart disease. How long after the myocardial infarction was blood sampled for measurement of serum lipids? Serum concentrations of cholesterol and its fractions are lower than the usual for a particular patient for up to 12 weeks after an acute myocardial infarction.2 In addition, serum LDL cholesterol was 3·4 mmol/L, which is the accepted limit2 for initiation of drug therapy in patients with coronary heart disease. Moreover, guidelines2 state that if LDL cholesterol at discharge in a patient who has had an acute myocardial infarction is equal to, or above 3·4 mmol/L, firm decisions about cholesterol-lowering therapy can be made, since the LDL concentration will probably be higher later, when the patient has not only recovered from the acute event but also re-established normal habits. Hence, Feenstra and colleagues’ patient probably had hypercholesterolaemia as a risk factor for ischaemic heart disease. In fact following the guidelines, drug treatment to lower cholesterol should be initiated at discharge. *L López-Lázaro, M García-Arenillas, A Portolés-Pérez, E Vargas-Castrillón, A Moreno-González Clinical Pharmacology Department, University Hospital San Carlos, 28040 Madrid, Spain (e-mail: “luislopez”[email protected])
THE LANCET • Vol 352 • December 12, 1998