New Publications in HIV : Archive

23 April 2009

Hepatology A clinical textbook

• Available as a free download, this medical textbook provides a comprehensive and up-to-date overview of research, diagnosis and treatment of hepatic conditions including HBV and HCV Link 28 April 2009

Tuberculosis pharmacotherapy: strategies to optimize patient care

Mitnick CD et al. Expert Opin. Pharmacother 2009;10:381–.401 • Review of the role that existing treatments and new agents could have in shortening or improving treatment for TB.
• Of the existing drugs, rifamycins have the greatest potential for shortening treatment and improving outcomes in HIV-positive individuals, without dramatic increases in toxicity.
• Conclusion: The challenge in TB pharmacotherapy is to devise well-tolerated, efficacious, short-duration regimens that can be used successfully in heterogeneous patient populations.
Link 28 April 2009

Immunopathogenesis of hepatic flare in HIV/hepatitis B virus (HBV)–coinfected individuals after the initiation of HBV-active antiretroviral therapy.

Crane M et al. J Infect Dis 2009;199:974–81. • This study investigated hepatic flare in ART-naïve HIV/HBV-coinfected individuals in Thailand who were starting HBV-active ART as part of a prospective clinical trial.
• HBV DNA and ALT levels at baseline were higher in patients with hepatic flare than in patients without (p=0.01).
• Conclusions: Raised HBV DNA and ALT levels prior to starting HBV-active ART are risk factors for hepatic flare. The pathogenesis of HF after starting HBV-active ART is probably consistent with immune restoration disease.
Link 29 April 2009

High mortality among patients with AIDS who received a diagnosis of tuberculosis in the first 3 months of antiretroviral therapy.

Koenig SP et al. Clin Infect Dis 2009;48:829–31. • This study investigated mortality among 201 patients with AIDS and TB in Haiti.
• Patients with a diagnosis of TB within the first 3 months of starting ART were 3.25 times more likely to die than other patients with AIDS and TB.
• Conclusion: Failure to recognize active TB when starting ART leads to increased mortality.
Link 29 April 2009

Assessment of liver fibrosis by transient elastography in persons with hepatitis C virus infection or HIV-hepatitis C virus coinfection.

Kirk GD et al. Clin Infect Dis 2009;48:963–72. • This study compared elastography with histology to stage liver fibrosis among HCV-infected and HIV/HCV-co-infected individuals in an urban, primarily black population.
• Elastography correctly staged liver fibrosis in 79–83% of participants compared with histology.
• Conclusions: Elastography was similar to histology in predicting fibrosis stage in most individuals. Elastography is a promising technique to expand liver disease screening and monitoring.
Link 29 April 2009

Changes in cancer mortality among HIV-infected patients: the Mortalité 2005 Survey.

Bonnet F et al. Clin Infect Disease • This study investigated cancer-related deaths among HIV-positive infected patients using data from a French national survey conducted in 2005 and compared the results with a similar 2000 survey.
• Compared with 2000 (29% of deaths were cancer related), there was a significant increase in cancer-related deaths (n= 344, 34% p=0.02). 134 of these deaths were and 210 were not AIDS related. The proportion of hepatitis-related cancers (6% vs 11%, p=0.03) and non-AIDS/hepatitis-related cancers (38% vs 50%, p=0.01) significantly increased from 2000 to 2005, compared with the proportion of AIDS-related cancer.
• Conclusions: There was an increasing proportion of lethal non-AIDS-related cancers from 2000 to 2005. Cancer prophylaxis, early diagnosis, and improved management should be included in routine long-term follow-up.
Link 29 April 2009

Editorial Malignancy-related deaths among HIV-infected patients.

Monforte AA. Clin Infect Disease 2009;48:640–1. • This study investigated cancer-related deaths among HIV-positive infected patients using data from a French national survey conducted in 2005 and compared the results with a similar 2000 survey.
• Compared with 2000 (29% of deaths were cancer related), there was a significant increase in cancer-related deaths (n= 344, 34% p=0.02). 134 of these deaths were and 210 were not AIDS related. The proportion of hepatitis-related cancers (6% vs 11%, p=0.03) and non-AIDS/hepatitis-related cancers (38% vs 50%, p=0.01) significantly increased from 2000 to 2005, compared with the proportion of AIDS-related cancer.
• Conclusions: There was an increasing proportion of lethal non-AIDS-related cancers from 2000 to 2005. Cancer prophylaxis, early diagnosis, and improved management should be included in routine long-term follow-up.
Link 06 May 2009

Upper-room ultraviolet light and negative air ionization to prevent tuberculosis transmission.

Escombe AR et al. PLoS Med 2009;6:e1000034. • This study investigated the efficacy of upper-room UV lights and negative air ionization for the prevention of airborne TB transmission using a guinea pig air-sampling model.
• Upper-room UV lights and negative air ionization prevented most airborne TB transmission.
• Conclusion: Upper-room UV light is an effective, low-cost intervention for TB infection control in high-risk clinical settings provided there is adequate mixing of room air.
Link 06 May 2009

Isoniazid preventive therapy, HAART and tuberculosis risk in HIV-infected adults in South Africa: a prospective cohort.

Golub JE et al. AIDS 2009;23:631–6. • This study investigated the effect of isoniazid preventive therapy (IPT), HAART or IPT and HAART on the incidence of TB in HIV-positive adults in South Africa.
• Compared to treatment-naive patients, HAART reduced the risk of TB by 64% (adjusted HR 0.36; 95% CI 0.25–0.51) and HAART after IPT reduced the risk by 89% (adjusted HR 0.11; 95% CI 0.02–0.78).
• Conclusion: IPT significantly reduced the risk of TB in adults receiving HAART in a high-incidence setting in South Africa and is an inexpensive and cost-effective strategy.
Link 06 May 2009

Effect of pulmonary tuberculosis on mortality in patients receiving HAART.

Westreich D et al. AIDS 2009;23:707–15. • This study estimated the effect of ongoing treatment for pulmonary TB at the time of starting HAART on subsequent risk of death.
• Comparing patients receiving HAART with and without treated pulmonary TB, the adjusted HR was 1.06 (95% CI 0.75–1.49), indicating no difference in mortality risk.
• Conclusion: The observed increase in death appeared not to be due to the presence of pulmonary TB but to confounding factors. Starting HAART soon after initiation of TB treatment is not likely to increase the risk of death.
Link 07 May 2009

Nevirapine pharmacokinetics in HIV-infected and HIV/HCV-coinfected individuals.

Vogel M et al. J Antimicrob Chemother 2009 Mar 6. • This study investigated the differences in NVP pK between patients with HIV infection and HIV/HCV co-infection that could be responsible for higher rates of hepatotoxicity.
• No difference was observed between the two groups in minimum and maximum drug levels or total drug exposure in terms of area under the curve.
• Conclusion: HCV co-infection does not alter the NVP pK in patients with preserved liver function.
Link 14 May 2009

Immunogenicity and safety of yellow fever vaccination for 102 HIV-infected patients.

Veit O, Niedrig M, Chapuis-Taillard C et al. Clin Infect Dis 2009;48:659–66. • This study investigated neutralization titres in 102 HIV-positive patients from the Swiss HIV Cohort Study who received yellow fever vaccine (17DV) and compared the results to HIV-negative individuals.
• During the first year after vaccination, fewer HIV-positive patients (65/78, 83%; p=0.01) than HIV-negative individuals had reactive neutralization titres, and these were significantly lower (p<0.001). Higher neutralization titres during the first year after vaccination were associated with undetectable HIV RNA levels, increasing CD4-cell count and female sex.
• Conclusions: Compared with HIV-negative individuals, HIV-positive patients responded to 17DV with lower reactive neutralization titres, more frequently demonstrated non-protective neutralization titres and experienced a more rapid decline in neutralization titres during follow-up. Vaccination with 17DV appears to be safe in HIV-positive patients who have high CD4-cell counts, although a rate of serious adverse events of up to 3% cannot be excluded.
Link 14 May 2009

Improved virologic response in chronic hepatitis C genotype 4 treated with nitazoxanide, peginterferon, and ribavirin.

Rossignol JF, Elfert A, El-Gohary Y et al. Gastroenterology 2009;136:856–62. • This Egyptian study investigated the efficacy and safety of nitazoxanide plus peginterferon alfa-2a, with or without ribavirin, for the treatment of HCV.
• The percentages of rapid (64% versus 38%, p=0.048) and sustained (79% versus 50%, p=0.023; respectively) virological response were significantly higher in patients who received nitazoxanide plus peginterferon alfa-2a and ribavirin than in those who received peginterferon alfa-2a plus ribavirin. Patients who received nitazoxanide plus peginterferon alfa-2a without ribavirin had intermediate rates of rapid (54%) and sustained (61%) virological response.
• Conclusions: The combination of nitazoxanide with peginterferon alfa-2a and ribavirin increased the percentage of patients with a rapid and sustained virological response compared with peginterferon plus ribavirin, without an increase in adverse events.
Link 14 May 2009

Nitazoxanide: beyond parasites toward a novel agent for hepatitis C.

Darling JM, Fried MW. Gastroenterology 2009;136:760–3. • This Egyptian study investigated the efficacy and safety of nitazoxanide plus peginterferon alfa-2a, with or without ribavirin, for the treatment of HCV.
• The percentages of rapid (64% versus 38%, p=0.048) and sustained (79% versus 50%, p=0.023; respectively) virological response were significantly higher in patients who received nitazoxanide plus peginterferon alfa-2a and ribavirin than in those who received peginterferon alfa-2a plus ribavirin. Patients who received nitazoxanide plus peginterferon alfa-2a without ribavirin had intermediate rates of rapid (54%) and sustained (61%) virological response.
• Conclusions: The combination of nitazoxanide with peginterferon alfa-2a and ribavirin increased the percentage of patients with a rapid and sustained virological response compared with peginterferon plus ribavirin, without an increase in adverse events.
Link 14 May 2009

Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trial.

Conde MB, Efron A, Loredo C et al. Lancet 2009;373:1183–9. • This study compared the addition of moxifloxacin or ethambutol to an isoniazid, rifampicin plus pyrazinamide regimen in adults with sputum smear-positive TB in Rio de Janeiro.
• At 8 weeks, cultures had converted to negative in 80% (59/74) of moxifloxacin patients versus 63% (45/72) in ethambutol patients (difference 17.2%; 95% CI: 2.8–31.7; p=0.03).
• Conclusion: Moxifloxacin improved culture conversion in the initial phase of TB therapy.
Link 15 May 2009

Treatment of chronic hepatitis C in Asia: when East meets West.

Yu ML, Chuang WL. J Gastroenterol Hepatol 2009;24:336–45. • This article reviews the optimum treatment of chronic HCV in the West and Asia.
• Currently, pegylated-interferon plus ribavirin is the standard of care. Increasing evidence indicates that Asians have a higher likelihood of achieving a sustained virological response than Caucasians with this regimen.
Link 05 June 2009

Response-guided therapy for chronic hepatitis C virus infection in patients coinfected with HIV: a pilot trial.

Van den Eynde E, Crespo M, Esteban JI et al. Clin Infect Dis 2009;48:1152–9. • This study investigated the feasibility of response-guided treatment for chronic HCV infection in patients co-infected with HIV in a tertiary-care hospital.
• Treatment duration (24, 48 or 60 weeks) was individualised on the basis of week 4 and week 12 virological response. The primary efficacy endpoint was sustained virologic response.
• Overall, 33 (55%) of 60 patients achieved a sustained virological response. In 17/19 patients (89.5%) who showed a rapid virological response, HCV was eradicated after 24 weeks of therapy. The rate of sustained virological response was significantly higher among patients with genotype 3 and low pre-treatment HCV RNA levels.
• Conclusion: Response-guided treatment was feasible and may be useful to optimize individual HCV therapy in patients co-infected with HIV.
Link 05 June 2009

Paradigm shift to address drug resistant tuberculosis in people living with HIV needed, and needed now.

Getahun H, Havlir D, Granich R et al. Trop Med Int Health 2009;14:376–8. • This editorial reviews the steps that should be taken to address the problem of drug-resistant TB in people living with HIV.
• Steps include an urgent need for a systematic review of the extent and magnitude of the convergence of the HIV and drug-resistant TB epidemics, particularly in Africa and Eastern Europe, and a greater emphasis on prevention, early diagnosis and treatment of TB, including drug-resistant TB.
Link 05 June 2009

Chronic hepatitis B: who to treat and which choice of treatment?

Di Marco V, Craxì A. Expert Rev Anti Infect Ther 2009;7:281–91. • This article reviews the treatment options for chronic hepatitis B and which patients should be treated.
• Treatment options are IFN-alpha, pegylated IFN, 3TC, adefovir dipivoxil, entecavir, telbivudine and TDF.
• Treatment choice should take into account the patient’s clinical features, antiviral efficacy, risk of resistance development, safety profile, method of administration and cost.
• Patients who should be treated include hepatitis B e antigen-positive patients with a prolonged phase of immune clearance and hepatitis B e antigen-negative patients with elevated levels of serum HBV DNA, abnormal alanine aminotransferase and histologic evidence of moderate or severe liver inflammation and/or fibrosis.
• Patients with compensated or decompensated cirrhosis should also be treated to prevent disease flare and improve liver function.
Link 05 June 2009

Hepatitis C virus virology and new treatment targets.

Meier V, Ramadori G. Expert Rev Anti Infect Ther 2009;7:329–50. • This article reviews the virology of HCV infection and new treatment targets.
• Almost half of patients who have chronic HCV infection cannot be cured with standard treatment (pegylated IFN-alpha and ribavirin). For these patients, there is currently no approved treatment.
• Due to recent progress in structure determination of HCV proteins and the development of a sub-genomic replicon system, specifically targeted antiviral therapies have been developed and are in preclinical and clinical trials
Link 05 June 2009

Prevention and treatment of HIV and other sexually transmitted infections among men who have sex with men and transgender populations: report of a technical consultation, 15–17 September 2008,

Geneva, Switzerland. WHO • This is a report of a WHO/UN meeting on the role the health sector should play in the prevention, treatment and care of HIV and other STIs among men who have sex with men (MSM), transgender people and their sexual partners.
• The key principles agreed were:
• A rights-based approach will guarantee the human rights of MSM and transgender people and will ensure that they and their sexual partners have the right to information and commodities that enable them to protect themselves against HIV and other STIs, protection from discrimination and criminalization and information on where to seek appropriate care.
• Knowing the epidemic and the response to it means knowing where infections are occurring, who is at risk or vulnerable and who is infected. It also means understanding the local, social and structural determinants of risk.
• The HIV and STI epidemics among MSM and transgender people cannot be addressed by the health sector alone. It requires partnerships and engagement across sectors (particularly legal and education) and with the MSM and transgender communities
Link 08 June 2009

Epidemiology of antituberculosis drug resistance 2002-07: an updated analysis of the Global Project on Anti-Tuberculosis Drug Resistance Surveillance.

Wright A, Zignol M, Van Deun A et al. Lancet 2009 Apr 15. [Epub ahead of print] • This study reports the latest data on the extent of worldwide TB drug resistance.
• Data on drug susceptibility were collected from 90,726 patients in 83 countries and territories.
• The median prevalence of resistance to any drug in new cases of TB was 11.1% (range 7.0–22.3%). The prevalence of multidrug resistance in new TB cases ranged from 0% in eight countries to 7% in two provinces in China and 6.8–22.3% in nine countries of the former Soviet Union.
• Five countries, all from the former Soviet Union, reported 25 cases or more of extensively drug-resistant (XDR) TB.
• Conclusions: MDR TB remains a threat to TB control in provinces in China and countries of the former Soviet Union. Data on drug resistance are unavailable in many countries, especially in Africa, emphasising the need to develop easier methods for TB resistance surveillance.
Link 08 June 2009

Scratching the surface of ignorance on MDR tuberculosis.

Borgdorff MW, Small PM. Lancet 2009 Apr 15. [Epub ahead of print] • This study reports the latest data on the extent of worldwide TB drug resistance.
• Data on drug susceptibility were collected from 90,726 patients in 83 countries and territories.
• The median prevalence of resistance to any drug in new cases of TB was 11.1% (range 7.0–22.3%). The prevalence of multidrug resistance in new TB cases ranged from 0% in eight countries to 7% in two provinces in China and 6.8–22.3% in nine countries of the former Soviet Union.
• Five countries, all from the former Soviet Union, reported 25 cases or more of extensively drug-resistant (XDR) TB.
• Conclusions: MDR TB remains a threat to TB control in provinces in China and countries of the former Soviet Union. Data on drug resistance are unavailable in many countries, especially in Africa, emphasising the need to develop easier methods for TB resistance surveillance.
Link 08 June 2009

Rifamycin-resistant Mycobacterium tuberculosis in the highly active antiretroviral therapy era: a report of 3 relapses with acquired rifampin resistance following alternate-day rifabutin and boosted protease inhibitor therapy.

Jenny-Avital ER, Joseph K. Clin Infect Dis 2009;48:1471–4. • This article reports three genetically confirmed cases of relapse with rifamycin-resistant TB following concurrent treatment with rifabutin and a RTV-boosted PI during a prior episode of drug-susceptible TB.
• Conclusion: Higher doses of rifabutin and a RTV-boosted PI as treatment for TB should be studied further.
Link 25 June 2009

Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial.

Zolopa AR, Andersen J, Komarow L et al. PLoS ONE 2009;4:e5575. • This clinical trial (ACTG A5164) compared early ART (given within 14 days of starting treatment for acute opportunistic infections) with deferred ART (given after treatment for acute opportunistic infection was completed).
• Early and deferred ART started a median of 12 and 45 days after starting treatment for acute opportunistic infections, respectively.
• The difference in the primary endpoint was not statistically significant: AIDS progression/death, 14% versus 24%; no progression but with incomplete viral suppression, 38% versus 31%; and no progression with optimal viral suppression, 48% versus 45% for early versus deferred treatment (p=0.22).
• However, early ART was associated with fewer AIDS progression/deaths (OR: 0.51; 95% CI: 0.27–0.94), a longer time to AIDS progression/death (HR: 0.53; 95% CI: 0.30–0.92), a shorter time to achieving a CD4 count >50 cells/mL (p<0.001) and no increase in adverse events.
• Conclusions: These results support the early initiation of ART in patients presenting with acute AIDS-related opportunistic infections.
Link 25 June 2009

A randomized trial comparing plasma drug concentrations and efficacies between 2 nonnucleoside reverse-transcriptase inhibitor-based regimens in HIV-infected patients receiving rifampicin: the N2R Study.

Manosuthi W, Sungkanuparph S, Tantanathip P et al. Clin Infect Dis 2009;48:1752–9. • This clinical trial (N2R) in patients with concurrent HIV-1 and TB infection receiving rifampicin compared EFV- and NVP-based ART.
• At weeks 6 and 12, the mean (± SD) concentrations 12 hours after dosing for EFV were 4.27±4.49 and 3.54±3.78 mg/L, respectively, and for NVP were 5.59±3.48 and 5.6±2.65 mg/L, respectively.
• At week 12, 3.1% of EFV patients and 21.3% NVP patients had drug concentrations that were less than the recommended minimum concentrations (OR: 8.396; 95% CI: 1.808–38.993; p=0.002).
• Conclusions. EFV-based ART was less compromised by concomitant use of rifampicin than NVP-based ART in patients with concurrent HIV-1 and TB infection. Low drug exposure and low body weight were important predictive factors for treatment failure.
Link 25 June 2009

Efavirenz and nevirapine interactions with rifampicin: resolving the dilemmas?

Lalloo UG. Clin Infect Dis 2009;48:1760–2. • This clinical trial (N2R) in patients with concurrent HIV-1 and TB infection receiving rifampicin compared EFV- and NVP-based ART.
• At weeks 6 and 12, the mean (± SD) concentrations 12 hours after dosing for EFV were 4.27±4.49 and 3.54±3.78 mg/L, respectively, and for NVP were 5.59±3.48 and 5.6±2.65 mg/L, respectively.
• At week 12, 3.1% of EFV patients and 21.3% NVP patients had drug concentrations that were less than the recommended minimum concentrations (OR: 8.396; 95% CI: 1.808–38.993; p=0.002).
• Conclusions. EFV-based ART was less compromised by concomitant use of rifampicin than NVP-based ART in patients with concurrent HIV-1 and TB infection. Low drug exposure and low body weight were important predictive factors for treatment failure.
Link 24 August 2009

Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection.

McHutchison JG, Everson GT, Gordon SC et al. N Engl J Med 2009;360:1827–38. • This study compared telaprevir, a PI specific for the HCV non-structural 3/4A serine protease, plus peginterferon alfa-2a and ribavirin with peginterferon alfa-2a and ribavirin in patients with HCV genotype 1 infection.
• Telaprevir was administered for 12 weeks with peginterferon alfa-2a and ribavirin for 12 (T12PR12), 24 (T12PR24) or 48 (T12PR48) weeks. Control patients received peginterferon alfa-2a and ribavirin for 48 weeks.
• The primary endpoint was a sustained virologic response (an undetectable HCV RNA level 24 weeks after the end of therapy).
• The rate of sustained virologic response was 41% in the control group compared with 61% in the T12PR24 group (p=0.02), 67% in the T12PR48 group (p=0.002) and 35% in the T12PR12 group.
• The rate of discontinuation due to adverse events was higher in the three telaprevir-based groups than the control group (21% versus 11%). Rash the most common reason for discontinuation.
• Conclusions: Telaprevir significantly improved the sustained virologic response rates in patients with HCV genotype 1 infection, although the rate of discontinuation due to adverse events as higher.
Link 24 August 2009

Telaprevir and peginterferon with or without ribavirin for chronic HCV infection.

Hézode C, Forestier N, Dusheiko G et al. N Engl J Med 2009;360:1839–50. • This study investigated telaprevir in treatment-naïve patients with chronic HCV genotype 1 infection.
• Patients were randomised to one of four regimens: telaprevir for 12 weeks plus peginterferon alfa-2a and ribavirin for 12 weeks (T12PR12), telaprevir for 12 weeks plus peginterferon alfa-2a and ribavirin for 24 weeks (T12PR24), telaprevir and peginterferon alfa-2a without ribavirin for 12 weeks (T12P12) and peginterferon alfa-2a and ribavirin for 48 weeks (control).
• The primary endpoint was a sustained virologic response (an undetectable HCV RNA level 24 weeks after the end of therapy).
• The rate of sustained virologic response was 46% in the control group compared with 36% in the T12P12 group (p=0.20), 48% in the T12PR12 and T12P12 groups combined (p=0.89), 60% in the T12PR12 group (p=0.12) and 69% in the T12PR24 group (p=0.004).
• Conclusions: Telaprevir for 12 weeks plus peginterferon alfa-2a and ribavirin for 24 weeks had a significantly higher rate of sustained virologic response than standard therapy.
Link 24 August 2009

Tuberculosis treatment and risk of stavudine substitution in first-line antiretroviral therapy.

Westreich DJ, Sanne I, Maskew M et al. Clin Infect Dis 2009;48:1617–23. • This study investigated the effect of TB treatment on stavudine toxicity among patients receiving first-line ART.
• Three exposure categories were considered: ongoing TB treatment at ART initiation, concurrent initiation of TB treatment and ART and TB treatment started after ART initiation. The outcome was single-drug stavudine substitution.
• Patients with ongoing and concurrent TB treatment were at increased risk of stavudine substitution, irrespective of stavudine dosage.
• TB treatment started after ART initiation had no effect on stavudine substitution risk.
• Conclusions: The risk of stavudine substitution was increased among patients who received TB treatment and was especially elevated during the period soon after ART initiation. In settings in which alternative ARVs are available, initiation of stavudine in patients receiving TB treatment may need to be reconsidered.
Link 25 August 2009

Uncontrolled viral replication as a risk factor for non-AIDS severe clinical events in HIV-infected patients on long-term antiretroviral therapy: APROCO/COPILOTE (ANRS CO8) cohort study.

Ferry T, Raffi F, Collin-Filleul F et al. J Acquir Immune Defic Syndr 2009;51:407–15. • This study investigated the risk factors for non-AIDS severe clinical events in HIV-infected patients on long-term ART in the APROCO/COPILOTE (ANRS CO8) cohort.
• During a median follow-up of 7.3 years, the incidence of non-AIDS events was higher than that of ART-related and AIDS-defining events (10.5, 3.6 and 2.6 per 100 patient-years, respectively).
• Bacterial (mainly airway) infections were the most frequent non-AIDS events (23.4%) followed by non-AIDS-defining malignancies and cardiovascular events (both 9.5%).
• Factors independently associated with the occurrence of a first non-AIDS event were age >60 years [HR: 2.1; 95% CI: 1.3–3.2] and CD4 <100 cells/mL (HR: 2.5; 95% CI: 1.8–3.6) plus plasma HIV RNA >4 log10 copies/mL at the time of the event (HR: 1.9; 95% CI: 1.5–2.5).
• Conclusion: Optimisation and permanent continuation of long-term ART in HIV-infected patients is the best strategy to prevent or reduce the occurrence of non-AIDS severe morbidity.
Link 16 September 2009

Risk of developing specific AIDS-defining illnesses in patients coinfected with HIV and hepatitis C virus with or without liver cirrhosis.

d'Arminio Monforte A, Cozzi-Lepri A, Castagna A et al. Clin Infect Dis 2009;49:612–22. • This study investigated the correlation between the occurrence of different AIDS-defining illnesses and chronic HCV infection or HCV-related liver cirrhosis in a large Italian cohort of HIV patients.
• Patients were stratified into two groups: those without HCV co-infection and with persistently normal aminotransferase levels and patients with HCV co-infection. The patients with HCV co-infection were stratified according to the diagnosis of liver cirrhosis.
• The incidence of new AIDS-defining illnesses was calculated as the number of events per 1000 person-years of follow-up.
• There were 496 AIDS-defining illnesses among 5397 patients with 25,105 person-years of follow-up (50% tested positive for HCV).
• HCV co-infection was associated with an increased risk of developing an AIDS-defining illness (adjusted relative rate [ARR]: 2.61; 95% CI: 1.88–3.61), bacterial infection (ARR: 3.15; 95% CI: 1.76–5.67), HIV-related disease (ARR: 2.68; 95% CI: 1.03–6.97) and mycotic disease (ARR: 3.87; 95% CI: 2.28–6.59).
• The rate of mycotic infection, bacterial infection, toxoplasmosis and HIV-related AIDS-defining illnesses among patients with cirrhosis were significantly higher than that among HIV patients without HCV co-infection and the risk was greater than that estimated for HCV antibody-positive patients without cirrhosis.
• Conclusions: HIV-related bacterial and mycotic infections are strongly associated with positive HCV serostatus and HCV-related cirrhosis. Clinicians should take into account these data when making decisions on initiation of ART for HCV-co-infected patients.
Link 16 September 2009

Coinfection with hepatitis C virus and HIV: more than double trouble.

Piroth L. Clin Infect Dis 2009;49:623–5. • This study investigated the correlation between the occurrence of different AIDS-defining illnesses and chronic HCV infection or HCV-related liver cirrhosis in a large Italian cohort of HIV patients.
• Patients were stratified into two groups: those without HCV co-infection and with persistently normal aminotransferase levels and patients with HCV co-infection. The patients with HCV co-infection were stratified according to the diagnosis of liver cirrhosis.
• The incidence of new AIDS-defining illnesses was calculated as the number of events per 1000 person-years of follow-up.
• There were 496 AIDS-defining illnesses among 5397 patients with 25,105 person-years of follow-up (50% tested positive for HCV).
• HCV co-infection was associated with an increased risk of developing an AIDS-defining illness (adjusted relative rate [ARR]: 2.61; 95% CI: 1.88–3.61), bacterial infection (ARR: 3.15; 95% CI: 1.76–5.67), HIV-related disease (ARR: 2.68; 95% CI: 1.03–6.97) and mycotic disease (ARR: 3.87; 95% CI: 2.28–6.59).
• The rate of mycotic infection, bacterial infection, toxoplasmosis and HIV-related AIDS-defining illnesses among patients with cirrhosis were significantly higher than that among HIV patients without HCV co-infection and the risk was greater than that estimated for HCV antibody-positive patients without cirrhosis.
• Conclusions: HIV-related bacterial and mycotic infections are strongly associated with positive HCV serostatus and HCV-related cirrhosis. Clinicians should take into account these data when making decisions on initiation of ART for HCV-co-infected patients.
Link 18 December 2009

A meta-analysis of the incidence of non-AIDS cancers in HIV-infected individuals.

Shiels MS et al. J Acquir Immune Defic Syndr 2009;52:611–22. • This meta-analysis estimated the standardized incidence ratios (SIRs) of non-AIDS cancers among HIV+ individuals compared with rates in the general population overall and stratified by gender, AIDS and HAART era using data from 18 studies.
• Among 625,716 HIV+ individuals, there were 4,797 non-AIDS cancers. SIRs for several cancers were increased. In particular, cancers associated with infections, such as anal (28; 95% CI: 21–35), liver (5.6; 95% CI: 4.0–7.7) and Hodgkin’s lymphoma (11; 95% CI: 8.8–15), and smoking, such as lung (2.6; 95% CI: 2.1–3.1), kidney (1.7; 95% CI: 1.3–2.2) and laryngeal (1.5; 95% CI: 1.1–2.0).
• AIDS was associated with greater SIRs for Hodgkin’s lymphoma, leukaemia, lung, brain and all non-AIDS cancers combined.
• Conclusions: HIV+ individuals may be at an increased risk of developing non-AIDS cancers, particularly those associated with infections and smoking. Certain cancers may be associated with advanced immune suppression.
Link 02 March 2010

Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial.

Lingappa JR et al. Lancet 2010 Feb 12. • This multicentre study in southern and east Africa investigated the effect of acyclovir on HIV-1 progression in ARV-naïve heterosexuals with dual HSV type 2 and HIV-1 infection and a CD4 cell count ≥200 cells/mm3.
• The effect of aciclovir on HIV-1 disease progression was defined by a primary composite endpoint of first occurrence of CD4 cell counts <200 cells/mm3, ART initiation or non-trauma related death.
• Acyclovir reduced the risk of HIV-1 disease progression by 16% (HR: 0.84; 95% CI: 0.71–0.98; p=0.03). In patients with CD4 cell counts ≥350 cells/mm3, acyclovir delayed the risk of CD4 cell counts falling to <350 cells/mm3 by 19% (HR: 0.81; 95% CI: 0.71–0.93; p=0.002).
• Conclusions: The role of suppression of HSV type 2 in reducing HIV-1 disease progression before starting ART warrants consideration.
Link 02 March 2010

Treating HIV infection with drugs for HSV-2 infection?

Buvé A, Lynen L. Lancet 2010 Feb 12. • This multicentre study in southern and east Africa investigated the effect of acyclovir on HIV-1 progression in ARV-naïve heterosexuals with dual HSV type 2 and HIV-1 infection and a CD4 cell count ≥200 cells/mm3.
• The effect of aciclovir on HIV-1 disease progression was defined by a primary composite endpoint of first occurrence of CD4 cell counts <200 cells/mm3, ART initiation or non-trauma related death.
• Acyclovir reduced the risk of HIV-1 disease progression by 16% (HR: 0.84; 95% CI: 0.71–0.98; p=0.03). In patients with CD4 cell counts ≥350 cells/mm3, acyclovir delayed the risk of CD4 cell counts falling to <350 cells/mm3 by 19% (HR: 0.81; 95% CI: 0.71–0.93; p=0.002).
• Conclusions: The role of suppression of HSV type 2 in reducing HIV-1 disease progression before starting ART warrants consideration.
Link 02 March 2010

Timing of Initiation of Antiretroviral Drugs during Tuberculosis Therapy.

Abdool Karim SS et al. N Engl J Med. 2010;362:697–706. • This open-label study conducted in South Africa investigated the optimal timing for starting ART in relation to tuberculosis treatment.
• Patients with tuberculosis and HIV infection were randomised to start ART either during (integrated: two groups) or after the completion of (sequential: one group) standard tuberculosis therapy. The primary end point was death from any cause.
• There was a reduction in the death rate with integrated therapy (5.4 deaths per 100 person-years), vs sequential therapy (12.1 per 100 person-years), a relative risk reduction of 56% (HR: 0.44; 95% CI: 0.25–0.79; p=0.003).
• Conclusions: The initiation of ART during tuberculosis therapy significantly improved survival.
Link 22 March 2010

An algorithm for tuberculosis screening and diagnosis in people with HIV.

Cain KP et al. N Engl J Med 2010;362:707–16. • This study, conducted in eight outpatient clinics in Cambodia, Thailand and Vietnam, compared the characteristics of patients diagnosed with TB with those of patients who did not have TB to derive an algorithm for TB screening and diagnosis.
• The presence of a cough for ≥2–3 weeks during the preceding 4 weeks had a sensitivity of 22–33% for detecting TB.
• The presence of cough or fever of any duration or night sweats lasting ≥3 weeks in the preceding 4 weeks was 93% sensitive and 36% specific for TB.
• In patients with any of these symptoms, a combination of two negative sputum smears, a normal chest radiograph and a CD4+ cell count of ≥350/mm3 helped to rule out a diagnosis of TB, whereas a positive diagnosis could be made only for patients with one or more positive sputum smears; mycobacterial culture was required for most other patients.
• Conclusions: In HIV+ patients, screening for TB should include questions about a combination of symptoms rather than just chronic cough.
Link 22 April 2010

Telaprevir for previously treated chronic HCV infection.

McHutchison JG et al. N Engl J Med 2010;362:1292–303. • This phase II study investigated telaprevir, a specific inhibitor of the HCV serine protease, in the treatment of chronic HCV genotype 1 infection.
• Treatment-naïve patients were randomly assigned to receive one of four regimens of telaprevir (1250 mg on day 1 then 750 mg every 8 hours), peginterferon alfa-2a (180 μg weekly) and ribavirin (dose according to body weight).
• The primary endpoint was the sustained virologic response (an undetectable HCV RNA level 24 weeks after the end of therapy).
• Conclusions: Telaprevir and peginterferon alfa-2a without ribavirin for 12 weeks had a significantly higher rate of sustained virologic response (69%) than standard therapy (46%; p=0.004).
Link 25 June 2010

Body mass index and risk of tuberculosis and death.

Hanrahan CF et al. AIDS 2010;24:1501–8. • This study investigated the effect of BMI on all-cause mortality and TB incidence among a cohort of HIV+ adults in Soweto, South Africa.
• Mortality rates (per 100 person-years) were 10.4 for baseline BMI of ≤18.5, 3.6 for baseline BMI 18.6–25, 1.7 for baseline BMI 25.1–30 and 1.6 for baseline BMI >30.
• Compared to those with normal BMI, overweight (adjusted HR: 0.59; 95% CI: 0.40–0.87) and obese (adjusted HR: 0.48; 95% CI: 0.29–0.80) individuals had a significantly reduced mortality risk and
• Incidence rates (per 100 person-years) of TB by baseline BMI were 7.3 for underweight, 6.0 for normal, 3.2 / for overweight and 1.9 for obese.
• Compared to those with normal BMI, those with overweight (adjusted HR: 0.56; 95% CI: 0.38–0.83) and obese BMI (adjusted HR: 0.33; 95% CI: 0.19–0.55) were at a significantly reduced risk of developing TB.
• Conclusion: HIV+ individuals with an obese or overweight BMI have a significantly reduced risk of both mortality and TB after adjusting for HAART use and CD4 cell count.
Link 05 July 2010

Effect of treating co-infections on HIV-1 viral load: a systematic review

Modjarrad K, Vermund SH. Lancet Infect Dis, 2010;10:455–63 • This systematic review assessed the effect of treating key co-infections on plasma HIV-1-RNA levels in resource-constrained countries.
• Standardised mean plasma VL decreased after the treatment of co-infecting pathogens in all 18 studies.
• Twelve of 14 studies with variance data reported significant differences in HIV VL before and after treatment.
• Conclusions: Although many of the VL reductions were ≤1.0 log10 copies/mL, even small changes in plasma HIV-RNA concentrations can slow HIV progression and could translate into population-level benefits in lowering the risk of HIV transmission.
Link