New Publications in HIV : Archive

20 April 2009

HIV RNA levels 6 months after ART initiation is a strong, independent predictor of subsequent survival in HIV-infected individuals in Sub-Saharan Africa

Marazzi M et al. CROI 2009;Abstract 597. Feb This study investigated the prognostic role of virological response to ART in patients from five DREAM-supported sites in three countries undergoing comprehensive treatment monitoring.

In a sensitivity analysis, when the multivariable model was additionally adjusted for WHO stage, HIV RNA >10,000 copies/mL remained independently predictive of death (vs <50 copies/mL, HR 3.97; 95%CI 1.75–8.00; p=0.001).

Conclusions: An HIV RNA <10,000 copies/mL level at 6 months (12–36 weeks) after ART initiation is a strong predictor of survival In a Sub-Saharan African setting.
Link 20 April 2009

Safety of switching nevirapine twice daily to nevirapine once daily in virologically suppressed patients.

Podzamczer D et al. J Acquir Immune Defic Syndr 2009 Feb 12. [Epub ahead of print] This randomized, open-label study investigated switching NVP once daily to twice daily with a primary endpoint of proportion of patients with ALT/aspartate transaminase (AST) ≥grade 3.

In the per-protocol analysis, 97.9% (once daily) and 99.3% (twice daily) of patients were event free (difference, 1.4%; 95CI –1.95–5.4%), demonstrating non-inferiority.

Conclusion: Switching to once-daily NVP was not inferior to continued twice daily NVP.
Link 20 April 2009

Gemini: a noninferiority study of saquinavir/ritonavir versus lopinavir/ritonavir as initial HIV-1 therapy in adults.

Walmsley S et al. J Acquir Immune Defic Syndr 2009 Feb 12. [Epub ahead of print] This, randomised, open-label, non-inferiority study compared SQV/r 1000 mg/100 mg twice daily and LPV/r 400 mg/100 mg twice daily, each with FTC/TDF 200 mg/300 mg every day.

SQV/r was noninferior to LPV/r: a similar proportion of patients had HIV-1 RNA levels <50 copies per mL at week 48 (64.7% vs 63.5%; estimated difference in proportion for noninferiority 1.14%; 96% CI –9.6 to11.9; p<0.012).

Conclusion: SQV/r was non-inferior to LPV/r in terms of virologic suppression at 48 weeks and had a better triglyceride profile in treatment-naïve patients.
Link 20 April 2009

Tenofovir se in human immunodeficiency virus-1-infected children in the United Kingdom and Ireland.

Riordan A et al. Pediatr Infect Dis J 2009;28:204–9. This study analysed the use of TDF in a cohort of HIV-1-infected children.

159 of 1253 children had taken TDF: 18% received >120% and 37% received <80% of the suggested paediatric dose (8 mg/kg). Twelve (7.5%) children experienced serious adverse events and stopped TDF permanently, 11 taking concurrent lopinavir-ritonavir, and 10 ddI; five had renal toxicity.

Conclusions: TDF seems to be an effective ARV in this paediatric cohort but considerable underdosing and overdosing occurs and a small number of children experienced serious adverse events.
Link 23 April 2009

High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients

Rey D et al. J Antimicrob Chemother 2009;63:380–8. • Randomized, open-label trial comparing lamivudine, tenofovirDF and nevirapine once daily with zidovudine/lamivudine and nevirapine twice daily in naive HIV-1-infected patients.
• The results showed an unexpected and high rate of early virological failures in patients treated with once-daily lamivudine, tenofovirDF and nevirapine, with a high incidence of resistance mutations to NNRTIs and K65R conferring broad cross-resistance to nucleoside analogues.
• Conclusion: once-daily combination of tenofovirDF, lamivudine and nevirapine should not be given as a first-line ARV therapy.
Link 23 April 2009

HIV monotherapy with ritonavir-boosted protease inhibitors: a systematic review.

Bierman WFW et al. AIDS 2009;23:279–91. • Systematic review of all PI monotherapy studies to assess the efficacy of ritonavir-boosted PI monotherapy.
• Conclusions: The overall efficacy of ritonavir-boosted PI monotherapy is inferior to HAART. The efficacy improves in patients started on monotherapy after suppressed HIV-RNA for at least 6 months. The majority of patients with prolonged viral suppression on HAART can successfully be treated with PI monotherapy.
Link 23 April 2009

HIV RNA levels 6 months after ART initiation is a strong, independent predictor of subsequent survival in HIV-infected individuals in Sub-Saharan Africa

Marazzi M et al. CROI 2009;Abstract 597. • This study investigated the prognostic role of virological response to ART in patients from five DREAM-supported sites in three countries undergoing comprehensive treatment monitoring.
• In a sensitivity analysis, when the multivariable model was additionally adjusted for WHO stage, HIV RNA >10,000 copies/mL remained independently predictive of death (vs <50 copies/mL, HR 3.97; 95%CI 1.75–8.00; p=0.001).
• Conclusions: An HIV RNA <10,000 copies/mL level at 6 months (12–36 weeks) after ART initiation is a strong predictor of survival In a Sub-Saharan African setting.
Link 28 April 2009

Safety of switching nevirapine twice daily to nevirapine once daily in virologically suppressed patients.

Podzamczer D et al. J Acquir Immune Defic Syndr 2009 Feb 12. [Epub ahead of print] • This randomized, open-label study investigated switching NVP once daily to twice daily with a primary endpoint of proportion of patients with ALT/aspartate transaminase (AST) ≥grade 3.
• In the per-protocol analysis, 97.9% (once daily) and 99.3% (twice daily) of patients were event free (difference, 1.4%; 95CI –1.95–5.4%), demonstrating non-inferiority.
• Conclusion: Switching to once-daily NVP was not inferior to continued twice daily NVP.
Link 28 April 2009

Gemini: a noninferiority study of saquinavir/ritonavir versus lopinavir/ritonavir as initial HIV-1 therapy in adults.

Walmsley S et al. J Acquir Immune Defic Syndr 2009 Feb 12. [Epub ahead of print • This, randomised, open-label, non-inferiority study compared SQV/r 1000 mg/100 mg twice daily and LPV/r 400 mg/100 mg twice daily, each with FTC/TDF 200 mg/300 mg every day.
• SQV/r was noninferior to LPV/r: a similar proportion of patients had HIV-1 RNA levels <50 copies per mL at week 48 (64.7% vs 63.5%; estimated difference in proportion for noninferiority 1.14%; 96% CI –9.6 to11.9; p<0.012).
• Conclusion: SQV/r was non-inferior to LPV/r in terms of virologic suppression at 48 weeks and had a better triglyceride profile in treatment-naïve patients.
Link 28 April 2009

Tenofovir se in human immunodeficiency virus-1-infected children in the United Kingdom and Ireland

Riordan A et al. Pediatr Infect Dis J 2009;28:204–9. • This study analysed the use of TDF in a cohort of HIV-1-infected children.
• 159 of 1253 children had taken TDF: 18% received >120% and 37% received <80% of the suggested paediatric dose (8 mg/kg). Twelve (7.5%) children experienced serious adverse events and stopped TDF permanently, 11 taking concurrent lopinavir-ritonavir, and 10 ddI; five had renal toxicity.
• Conclusions: TDF seems to be an effective ARV in this paediatric cohort but considerable underdosing and overdosing occurs and a small number of children experienced serious adverse events.
Link 28 April 2009

Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells.

Mitsuyasu RT et al. Nat Med 2009;15:285–92. • This randomized, double-blind, placebo-controlled, phase 2 study investigated the evaluated the safety and efficacy of anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ haematopoietic progenitor cells.
• There were no OZ1-related adverse events and there was no statistically significant difference in viral load between OZ1 and placebo at the primary endpoint. However, HIV-1 viral loads were consistently lower in the OZ1 group for all analyses.
• Conclusion: Cell-delivered gene transfer is safe and biologically active and can be developed as a conventional therapeutic product.
Link 28 April 2009

Adaptation of HIV-1 to human leukocyte antigen class I.

Kawashima Y et al. Nature 2009 Feb 25. [Epub ahead of print] • This study analysed viral sequences and HLA alleles from >2,800 subjects in five continents.
• The results showed strong evidence of HIV adaptation to HLA at a population level.
• Conclusion: The process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.
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

The challenge of finding a cure for HIV infection.

Richman DD et al. Science 2009;323:1304–7. • This article reviews the current understanding of suppressive ART, the latent viral reservoir, and the needs for and challenges of attacking this reservoir to achieve a cure. Link 29 April 2009

Do benefits of earlier antiretroviral treatment initiation outweigh harms for individuals at risk for poor adherence?

Braithwaite RS et al. Clin Infect Dis 2009;48:822–6. • This study used a validated computer simulation of HIV disease progression to compare alternative treatment thresholds for patients with suboptimal adherence.
• Earlier treatment increased life expectancy across a wide range of adherence (50–100%).
• Conclude: Delaying treatment for patients with suboptimal adherence may not always be appropriate.
Link 29 April 2009

Editorial Balancing adherence concerns with the risks of HIV disease progression.

Johnson SC. Clin Infect Dis 2009;48:827–8. • This study used a validated computer simulation of HIV disease progression to compare alternative treatment thresholds for patients with suboptimal adherence.
• Earlier treatment increased life expectancy across a wide range of adherence (50–100%).
• Conclude: Delaying treatment for patients with suboptimal adherence may not always be appropriate.
Link 06 May 2009

Response to zidovudine/didanosine-containing combination antiretroviral therapy among HIV-1 subtype C-infected adults in Botswana: two-year outcomes from a randomized clinical trial.

Bussmann H et al. J Acquir Immune Defic Syndr 2009 Mar 11. [Epub ahead of print] • The Tshepo study was a randomized open-label trial in treatment-naïve, HIV-1 subtype C-infected adults that compared the efficacy and tolerability PI-sparing combination ARV with NRTIs (ZDV+3TC, ZDV+ddI and d4T+3TC) and NNRTIs (NVP and EFV) and different adherence strategies (standard care versus an intensified adherence strategy)
• The ZDV/ddI arms were discontinued due to inferiority in the primary endpoint (VF and resistance).
• The proportion of patients with VF and genotypic resistance mutations was 11% for ZDV/ddI-based ART versus 2% in those receiving either ZDV/3TC- or d4T/3TC-based ART (p=0.002).
• Conclusions: The preliminary results showed that NNRTI-based ART had excellent efficacy and tolerability in HIV-1 subtype C-positive adults. However, ZDV/ddI-containing ART was inferior to the dual NRTIs d4T/3TC or ZDV/3TC when used with an NNRTI as first-line ART.
Link 07 May 2009

Should HIV therapy be started at a CD4 cell count above 350 cells/microl in asymptomatic HIV-1-infected patients?

Sabin CA, Phillips AN. Curr Opin Infect Dis 2009;22:191–7. • The article reviews the data on the optimal time to initiate HAART in HIV-positive individuals with a CD4 cell count >350 cells/μL.
• Although there is little randomized data, the results of several observational studies generally support earlier initiation of HAART.
• Conclusions: Data generally support starting HAART in patients with CD4 cell counts >350 cells/μL. However, it is not possible to rule out possible long-term detrimental effects of earlier use of HAART until the results from fully powered randomized trials are available.
Link 14 May 2009

Is the interruption of antiretroviral treatment during pregnancy an additional major risk factor for mother-to-child transmission of HIV type 1?

Galli L, Puliti D, Chiappini E et al. Clin Infect Dis 2009;48:1310–7. • This prospective study investigated the effects of discontinuing ART during pregnancy on the rate of mother-to-child transmission.
• Among 937 HIV-positive pregnant women, ART was interrupted in 81 (8.6%) in the first and 11 (1.2%) in the third trimester. The rate of mother-to-child transmission was 1.3% (95% CI: 0.7–2.3%) overall, 4.9% (95% CI: 1.9–13.2%) with first-trimester interruption and 18.2% (95% CI, 4.5%–72.7%) with third- trimester interruption.
• Conclusion: Discontinuing ART during pregnancy increases the rate of mother-to-child transmission of HIV-1.
Link 14 May 2009

Effect of HIV-1 subtype on virologic and immunologic response to starting highly active antiretroviral therapy.

Geretti AM, Harrison L, Green H et al. Clin Infect Dis 2009;48:1296–305. • This study used data from the linked UK Collaborative Group on HIV Drug Resistance and the UK Collaborative HIV Cohort Study databases to investigate the effect of HIV-1 subtype (B: np1550; C: np272; A: np66; circulating recombinant form AG: np57 and D: np41) on virological and immunological response in treatment-naïve patients starting HAART.
• In adjusted analyses, VL was suppressed more rapidly in patients with subtype C (HR: 1.16; 95% CI: 1.01–1.33; p=0.04) and subtype A (HR: 1.35; 95% CI: 1.04–1.74; p=0.02) relative to subtype B. CD4-cell count recovery rates were similar for all subtypes.
• Conclusions: Patients infected with prevalent non-B subtypes were as likely to achieve VL suppression as those infected with subtype B and showed comparable rates of CD4 cell count recovery.
Link 14 May 2009

Are all subtypes created equal? The effectiveness of antiretroviral therapy against non–subtype B HIV-1

Pond SLK, Smith DM. Clin Infect Dis 2009;48:1306–9. • This study used data from the linked UK Collaborative Group on HIV Drug Resistance and the UK Collaborative HIV Cohort Study databases to investigate the effect of HIV-1 subtype (B: np1550; C: np272; A: np66; circulating recombinant form AG: np57 and D: np41) on virological and immunological response in treatment-naïve patients starting HAART.
• In adjusted analyses, VL was suppressed more rapidly in patients with subtype C (HR: 1.16; 95% CI: 1.01–1.33; p=0.04) and subtype A (HR: 1.35; 95% CI: 1.04–1.74; p=0.02) relative to subtype B. CD4-cell count recovery rates were similar for all subtypes.
• Conclusions: Patients infected with prevalent non-B subtypes were as likely to achieve VL suppression as those infected with subtype B and showed comparable rates of CD4 cell count recovery.
Link 14 May 2009

Effect of Early versus Deferred Antiretroviral Therapy for HIV on Survival.

Kitahata MM, Gange SJ, Abraham AG et al. N Engl J Med 2009 Apr 1. [Epub ahead of print] • This study investigated the optimal time for starting ART in asymptomatic patients by conducting two parallel analyses involving 17,517 treatment-naïve patients in the US and Canada from 1996–2005. Patients were stratified by CD4-cell count (351–500 or >500 cells/mm3) at the start of ART.
• In the first analysis, which included 8,362 patients, 2,084 (25%) started therapy at a CD4-cell count of 351–500 cells/mm3 and 6,278 (75%) delayed treatment. There was an increased risk of death of 69% with delayed versus early treatment (RR: 1.69; 95% CI: 1.26–2.26; p<0.001).
• In the second analysis, which included 9,155 patients, 2,220 (24%) started treatment at a CD4-cell count of >500 cells/mm3 and 6,935 (76%) delayed treatment. There was an increased risk of death of 94% with delayed versus early treatment (RR: 1.94; 95% CI: 1.37–2.79; p<0.001).
• Conclusions: Early initiation of ART significantly improved survival compared with delayed treatment.
Link 14 May 2009

When to Start Antiretroviral Therapy — Ready When You Are?

Sax PE, Baden LR. N Engl J Med 2009 Apr 1. [Epub ahead of print] • This study investigated the optimal time for starting ART in asymptomatic patients by conducting two parallel analyses involving 17,517 treatment-naïve patients in the US and Canada from 1996–2005. Patients were stratified by CD4-cell count (351–500 or >500 cells/mm3) at the start of ART.
• In the first analysis, which included 8,362 patients, 2,084 (25%) started therapy at a CD4-cell count of 351–500 cells/mm3 and 6,278 (75%) delayed treatment. There was an increased risk of death of 69% with delayed versus early treatment (RR: 1.69; 95% CI: 1.26–2.26; p<0.001).
• In the second analysis, which included 9,155 patients, 2,220 (24%) started treatment at a CD4-cell count of >500 cells/mm3 and 6,935 (76%) delayed treatment. There was an increased risk of death of 94% with delayed versus early treatment (RR: 1.94; 95% CI: 1.37–2.79; p<0.001).
• Conclusions: Early initiation of ART significantly improved survival compared with delayed treatment.
Link 14 May 2009

Safe substitution to zidovudine among HIV-infected patients initiated on stavudine-containing highly active antiretroviral therapy from a resource-limited setting.

Kumarasamy N, Venkatesh KK, Devaleenol B et al. Int J Infect Dis 2009 Mar 26. [Epub ahead of print] • This retrospective study in Southern India investigated the substitution of d4T with AZT in patients who started d4T-based HAART due to the development of anaemia.
• During the study period, half of 619 patients who started d4T-based HAART subsequently received AZT. After substitution, three patients (2.7%) who substituted after <6 months and one patient (0.6%) who substituted between 6–12 months developed anemia. Patients who substituted after <6 months had significantly higher median CD4-cell counts at 1- and 6-month follow-up than patients who substituted at 6–12 months (p<0.05).
• Conclusion: In settings where TDF is either expensive or not available, starting d4T followed by prompt substitution with AZT can be a safe option for anaemic patients.
Link 05 June 2009

Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies.

Lancet 200918;373:1352–63. • This study analysed data from 15 cohort studies of ARV-naïve patients who started ART with a CD4-cell count <550 cells/μL to compare the effect of deferred with immediate initiation of ART on rates of AIDS and death and on death alone.
• Delaying ART until a CD4 cell count of 251–350 cells/μL was associated with higher rates of AIDS and death than starting treatment in the range 351–450 cells/μL (HR: 1•28; 95% CI: 1•04–1•57). The adverse effect of delayed treatment increased with decreasing CD4-cell count threshold.
• Delayed initiation of ART was also associated with higher mortality rates, although effects on mortality were less marked than effects on AIDS and death (HR: 1•13; 95% CI: 0•80–1•60, for delayed initiation at CD4 cell count 251–350 cells/μL vs 351–450 cells/μL).
• Conclusion: The results suggest that 350 cells/μL should be the minimum threshold for initiation of ART.
Link 05 June 2009

Should the CD4 threshold for starting ART be raised?

Wood R, Lawn SD. 200918;373:1314–6. • This study analysed data from 15 cohort studies of ARV-naïve patients who started ART with a CD4-cell count <550 cells/μL to compare the effect of deferred with immediate initiation of ART on rates of AIDS and death and on death alone.
• Delaying ART until a CD4 cell count of 251–350 cells/μL was associated with higher rates of AIDS and death than starting treatment in the range 351–450 cells/μL (HR: 1•28; 95% CI: 1•04–1•57). The adverse effect of delayed treatment increased with decreasing CD4-cell count threshold.
• Delayed initiation of ART was also associated with higher mortality rates, although effects on mortality were less marked than effects on AIDS and death (HR: 1•13; 95% CI: 0•80–1•60, for delayed initiation at CD4 cell count 251–350 cells/μL vs 351–450 cells/μL).
• Conclusion: The results suggest that 350 cells/μL should be the minimum threshold for initiation of ART.
Link 05 June 2009

Emerging Concepts in the Immunopathogenesis of AIDS.

Douek DC, Roederer M, Koup RA. 2009;60:471–84 • This article reviews the role immune activation plays in HIV immunopathogenesis, how this could be mediated directly by HIV replication in the gut mucosal barrier, how HIV affects multiple T-cell functions and phenotypes and how chronic HIV replication induces immune pathways to negatively regulate certain functions in HIV-specific T-cells. 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

A randomized, controlled trial of initial anti-retroviral therapy with abacavir/lamivudine/zidovudine twice-daily compared to atazanavir once-daily with lamivudine/zidovudine twice-daily in HIV-infected patients over 48 weeks (ESS100327, the ACTION Study)

Kumar PN, Salvato P, Lamarca A et al. AIDS Res Ther 2009 Apr 9;6:3. • The ACTION study investigated whether alternate treatment options may meet the needs of both general and special patient populations for whom traditional first-line regimens are unsuitable.
• This 48-week study compared the safety and efficacy of a triple NRTI regimen (ABC/3TC/ZDV twice daily) with a PI plus dual NRTI regimen (ATV once daily + 3TC/ZDV twice-daily) in treatment-naïve patients.
• ABC/3TC/ZDV was non-inferior to ATV+3TC/ZDV, with 62% vs 59% of patients achieving a VL <50 copies/mL at week 48 (95% CI –5.9–10.4). Similar results were observed in patients with baseline VL<100,000 copies/mL (66% vs 59%; 95% CI: –5.6–19.5). However, the non-inferiority criterion was not meet in patients with baseline VL ≥100,000 copies/mL (39% vs 60%; 95% CI: –49.2–7.4).
• Conclusions: ABC/3TC/ZDV demonstrated comparable virological efficacy to ATV+3TC/ZDV. In patients with a baseline VL ≥100,000 copies/mL, ATV+3TC/ZDV showed better virological efficacy.
Link 08 June 2009

CD4 cell-guided scheduled treatment interruptions in HIV-infected patients with sustained immunologic response to HAART.

Maggiolo F, Airoldi M, Callegaro A et al. AIDS 2009;27:799–807 • The LOTTI study compared continuous HAART with a CD4-cell-guided scheduled treatment interruption (STI) strategy. The primary endpoint was the development of an opportunistic disease, death from any cause or the occurrence of diseases, other than opportunistic, requiring hospital admission.
• Patients in the STI group stopped therapy for a total of 241 STI cycles and the mean time off therapy was 65.3% of the follow-up period.
• The primary endpoint occurred in 12.1% of patients on STI and in 11.6% of controls (OR: 1.05; 95% CI: 0.54–2.05). A higher proportion of patients in the STI group were diagnosed with pneumonia (p=0.037), while clinical events influencing cardiovascular risk were significantly (p<0.0001) more frequent among controls.
• Conclusions: The two strategies may be considered clinically equivalent. CD4-cell-guided STIs are a possible alternative for chronically infected patients responding to HAART provided that CD4-cell decrements are steadily maintained above a safe threshold.
Link 08 June 2009

Is it smart to continue to study treatment interruptions?

AIDS 2009;27:757–9. Hirschl B, Flanigan T. • The LOTTI study compared continuous HAART with a CD4-cell-guided scheduled treatment interruption (STI) strategy. The primary endpoint was the development of an opportunistic disease, death from any cause or the occurrence of diseases, other than opportunistic, requiring hospital admission.
• Patients in the STI group stopped therapy for a total of 241 STI cycles and the mean time off therapy was 65.3% of the follow-up period.
• The primary endpoint occurred in 12.1% of patients on STI and in 11.6% of controls (OR: 1.05; 95% CI: 0.54–2.05). A higher proportion of patients in the STI group were diagnosed with pneumonia (p=0.037), while clinical events influencing cardiovascular risk were significantly (p<0.0001) more frequent among controls.
• Conclusions: The two strategies may be considered clinically equivalent. CD4-cell-guided STIs are a possible alternative for chronically infected patients responding to HAART provided that CD4-cell decrements are steadily maintained above a safe threshold.
Link 08 June 2009

The nucleoside backbone affects durability of efavirenz- or nevirapine-based highly active antiretroviral therapy in antiretroviral-naive individuals.

Annan NT, Nelson M, Mandalia S et al. J Acquir Immune Defic Syndr 2009 Apr 6. [Epub ahead of print] • This study investigated the efficacy of NNRTI-based regimens (NVP or EFV) and the effect of year treatment started, NRTI backbone, sex and ethnicity on treatment outcome in ARV-naïve patients starting HAART.
• Of 994 patients, 73% started EFV- and 27% NVP-based regimens. There was no difference between the two groups for virological success (EFV, 71%; NVP, 72%; p=0.77) or treatment failure (EFV, 23%; NVP, 26%; p=0.58).
• The year HAART was started was significantly associated with virological success and treatment failure (p<0.001). The likelihood of virological success for d4T/3TC was 52% [HR: 1.52; 95% CI: 1.17–1.97; p=0.002]. The non-thymidine analogues were least likely to be associated with virological success (HR: 0.62; 95% CI: 0.48–0.80; p<0.001). Sex and ethnicity were not associated with treatment outcome.
• Conclusions: There was no significant difference between NVP and EFV for time to virological success or treatment failure. Year of starting HAART and NRTI backbones were significant predictors of virological success and treatment failure.
Link 08 June 2009

Clinical experience with the combined use of lopinavir/ritonavir and rifampicin.

L'homme RF, Nijland HM, Gras L et al. AIDS 2009;27:863–5. • In this study of 34 patients treated concomitantly with LPV/r and rifampicin, only 15% used the recommended increased dose of LPV/r.
• Of the patients on a non-adjusted dose of LPV/r, 67% had a sub-therapeutic LPV plasma concentration and 38% had a detectable VL.
• Forty percent of patients on an increased dose of LPV/r prematurely stopped the drug combination because of adverse events.
• Conclusion: Combined use of LPV/r and rifampicin is challenging because there has to be a balance between suboptimal efficacy and toxicity.
Link 08 June 2009

Second-line therapy.

HIV & AIDS Treatment in Practice Issue 134, April 2009, 2009 • This newsletter reviews second-line therapy in resource-constrained settings.
• Lack of VL testing means that many patients who are failing treatment go undetected for long periods, resulting in high levels of drug resistance, especially to NRTIs.
• The WHO recommends two NRTI backbones (TDF + 3TC or FTC, or ABC/ddI) and a boosted PI (LPV/r or ATV/r) for use in second-line therapy.
• Responses to second-line regimens have been good in the small cohorts of patients reported so far, but there is very little information about the effects of these recommended regimens.
• Studies are looking at other approaches, including boosted PI monotherapy or using new classes (e.g. a PI and an integrase inhibitor).
• All second-line drugs are significantly more costly than first-line drugs, so preventing failure of first-line treatment is critical.
Link 08 June 2009

Simplification strategies to reduce antiretroviral drug exposure: progress and prospects.

McKinnon JE, Mellors JW, Swindells S. Antivir Ther 2009;14:1–12. • This article reviews progress in the simplification of ART, recent clinical trial results and future prospects. Link 08 June 2009

The variability and predictors of quality of AIDS care services in Brazil.

Nemes MI, Melchior R, Basso CR et al. BMC Health Serv Res 2009;9:51. • This article reports the results of a survey of 336 AIDS health centres in seven Brazilian states conducted in 2002. The survey consisted of a multiple-choice questionnaire comprising 107 parameters of service inputs and processes for delivering care, with responses assessed according to their likely impact on service quality.
• Parameters of service delivery processes were more important than those relating to service inputs for determining quality.
• Predictors of quality services included larger care sites, specialization for HIV/AIDS and location within large municipalities.
• Conclusions: Service quality was highly variable. Many sites had deficiencies in service delivery processes that could benefit from quality improvement initiatives. A set of service delivery indicators were identified that could be used for routine monitoring of HIV/AIDS service delivery in Brazil and potentially in other similar settings.
Link 08 June 2009

Maraviroc: perspectives for use in antiretroviral-naive HIV-1-infected patients.

Vandekerckhove L, Verhofstede C, Vogelaers D. J Antimicrob Chemother 2009 Apr 18. [Epub ahead of print] • This article reviews the prospective and retrospective analyses of the MERIT data and highlights the impact of these results on the use of maraviroc in clinical practice.
• Due to its mode of action, it is expected that maraviroc will be effective only in a subpopulation of patients harbouring the R5 virus.
• Maraviroc has not met the criteria of potency, durability and convenience in a prospective analysis required for first-line regimens and cannot be advocated for clinical use in treatment-naive patients.
• Whether maraviroc can be used together with other drugs with a low genetic barrier, such as non-nucleoside analogues or integrase inhibitors in first-line regimens is currently unclear.
• The favourable lipid profile and tolerability support the use of maraviroc as a safe alternative in a consolidation or maintenance regimen after achieving full virological suppression, especially in patients experiencing side effects on NNRTIs, PIs or integrase inhibitors.
Link 25 June 2009

Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys.

Johnson PR, Schnepp BC, Zhang J et al. Nat Med 2009 May 17. [Epub ahead of print] • This study reports the use of a simian immunodeficiency virus (SIV) model to deliver to muscle an adeno-associated virus gene transfer vector expressing antibodies or antibody-like immunoadhesins with predetermined SIV specificity.
• SIV-specific molecules were endogenously synthesized in myofibres and passively distributed to the circulatory system, resulting in long-lasting neutralizing activity in serum and complete protection against intravenous challenge with virulent SIV.
• This strategy bypasses the adaptive immune system and holds considerable promise as a unique approach to developing an effective HIV vaccine.
Link 25 June 2009

HIV viremia and changes in kidney function.

Longenecker CT, Scherzer R, Bacchetti P et al. AIDS 2009;23:1089–96. • This prospective cohort study evaluated the effect of HIV infection on longitudinal changes in kidney function (measured by glomerular filtration rate) and identified independent predictors of kidney function changes in HIV-infected individuals.
• HIV infection was associated with both clinical decline (OR: 2.2; 95% CI: 1.3–3.9; p=0.004) and clinical improvement (OR: 7.3; 95% CI: 3.9–13.6; p≤0.0001). A decrease in HIV VL during follow-up was independently associated with clinical improvement; conversely, higher VL at baseline and during follow-up was associated with clinical decline.
• Conclusion: Compared with controls, HIV-infected individuals were more likely to have clinical decline and clinical improvement in kidney function during 5 years of follow-up. The extent of viraemic control was strongly associated with longitudinal changes in kidney function.
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 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

Efavirenz dose reduction is safe in patients with high plasma concentrations and may prevent efavirenz discontinuations.

Van Luin M, Gras L, Richter C et al. J Acquir Immune Defic Syndr 2009 Jul 10. [Epub ahead of print] • This study investigated whether EFV dose reduction in patients with high plasma concentrations prevents toxicity-induced EFV discontinuations.
• HIV-infected patients with a high EFV plasma concentration (≥4.0 mg/L) while using EFV 600 mg once daily as part of HAART regimen were selected from the AIDS Therapy Evaluation in The Netherlands cohort study.
• Of 180 patients with high plasma EFV levels, 47 subsequently had the dose reduced from 600 mg to 400 mg once-daily, which resulted in a 41% decrease in the median EFV plasma concentration.
• At week 48, the Kaplan-Meier estimated cumulative incidence of toxicity-induced EFV discontinuations was 11.5% in patients on the standard dose versus 2.3% in patients who had a dose reduction (p=0.066, log-rank test).
• Dose reduction was not associated with loss of virological suppression.
• Conclusions: Dose reduction may prevent toxicity-induced discontinuations in patients with high EFV plasma concentrations without compromising virological efficacy.
Link 25 August 2009

Modified directly observed antiretroviral therapy compared with self-administered therapy in treatment-naive HIV-1-infected patients: a randomized trial.

Gross R, Tierney C, Andrade A et al. Arch Intern Med 2009;169:1224–32. • This open-label, randomized trial investigated whether modified directly observed therapy (mDOT) improves initial ART success versus self-administered therapy.
• Eighty-two patients received mDOT and 161 self-administered therapy with LPV/r, FTC and either extended-release d4T or TDF (all once daily). The primary outcome was virologic success at week 24 and secondary outcomes were virologic success, clinical progression and adherence at week 48.
• Over 24 weeks, mDOT had greater virologic success (0.91; 95% CI: 0.81–0.95) than self-administered therapy (0.84; 95% CI: 0.77–0.89), but the difference (0.07; lower bound 95% CI: –0.01) did not reach the prespecified threshold of 0.075.
• Over 48 weeks, there was no significant difference in virologic success between mDOT (0.72; 95% CI: 0.61–0.81) and self-administered therapy (0.78; 95% CI: 0.70–0.84) (difference, –0.06; 95% CI: –0.18–0.07; p=0.19).
• Conclusions: The potential benefit of mDOT was marginal and not sustained after discontinuation and should not be incorporated routinely for care of treatment-naïve patients.
Link 16 September 2009

Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial.

Lennox JL, Dejesus E, Lazzarin A et al. Lancet 2009 Jul 31 [Epub ahead of print] • This study compared the safety and efficacy of RAL with EFV as part of ART for treatment-naive patients.
• Patients (n=556) were randomised to 400 mg oral RAL twice daily (n=281) or 600 mg oral EFV (282) once daily, in combination with TDF and FTC. Three patients were not treated.
• The primary efficacy endpoint was a viral RNA concentration <50 copies/mL at week 48 in the per-protocol population.
• In the RAL group, 86.1% (n=241 patients) and 81.9% (n=230) in the EFV group patients achieved the primary endpoint (difference 4.2%; 95% CI: –1.9 to 10.3).
• The time to viral suppression was shorter for RAL than EFV (log-rank test p<0.0001).
• Significantly fewer drug-related adverse events occurred with RAL (n=124 [44.1%]) than EFV (n=217 [77.0%]; difference –32.8%; 95% CI: –40.2 to –25.0; p<0.0001).
• Conclusions: RAL-based ART had rapid and potent ARV activity, which was non-inferior to that of EFV at week 48. RAL is a well-tolerated alternative to EFV as part of ART in treatment-naïve patients.
Link 16 September 2009

Raltegravir: a new choice in HIV and new chances for research.

Emery S, Winston A. Lancet 2009 Jul 31 [Epub ahead of print] • This study compared the safety and efficacy of RAL with EFV as part of ART for treatment-naive patients.
• Patients (n=556) were randomised to 400 mg oral RAL twice daily (n=281) or 600 mg oral EFV (282) once daily, in combination with TDF and FTC. Three patients were not treated.
• The primary efficacy endpoint was a viral RNA concentration <50 copies/mL at week 48 in the per-protocol population.
• In the RAL group, 86.1% (n=241 patients) and 81.9% (n=230) in the EFV group patients achieved the primary endpoint (difference 4.2%; 95% CI: –1.9 to 10.3).
• The time to viral suppression was shorter for RAL than EFV (log-rank test p<0.0001).
• Significantly fewer drug-related adverse events occurred with RAL (n=124 [44.1%]) than EFV (n=217 [77.0%]; difference –32.8%; 95% CI: –40.2 to –25.0; p<0.0001).
• Conclusions: RAL-based ART had rapid and potent ARV activity, which was non-inferior to that of EFV at week 48. RAL is a well-tolerated alternative to EFV as part of ART in treatment-naïve patients.
Link 22 October 2009

Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.

The ART-LINC of IeDEA Study Group. AIDS 2009;23:1867–74 • This study investigated switching from NNRTI-based first-line regimens to PI-based regimens in 17 ART programmes in Africa, South America and Asia and compared times to switching, CD4 cell counts at switching and adjusted HRs for switching.
• All sites monitored CD4 cell count and had access to second-line ART and 10 sites monitored VL. A total of 20,113 patients, including 6369 (31.7%) patients from 10 programmes with access to VL monitoring, were analysed; 576 patients (2.9%) switched.
• Median time to switching was 16.3 months (interquartile range 10.1–26.6) in programmes with VL monitoring and 21.8 months (interquartile range 14.0–21.8) in those without (p<0.001).
• Median CD4 cell count at switching was 161 cells/μL (interquartile range 77–265) in programmes with VL monitoring and 102 cells/μL (interquartile range 44–181) in those without (p<0.001).
• Conclusion: In resource-limited settings, switching to second-line regimens tends to occur earlier and at higher CD4 cell counts in ART programmes with VL monitoring versus those without.
Link 26 October 2009

Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand.

Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S et al. N Engl J Med 2009;361 • This community-based, randomised, multicentre, double-blind, placebo-controlled trial evaluated a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) in combination with a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E).
• The study included 16,402 healthy men and women aged 18–30 years primarily at heterosexual risk for HIV infection.
• There was a trend toward the prevention of HIV-1 infection, with an efficacy of 26.4% (95% CI: −4.0–47.9; p=0.08) in the ITT population and 26.2% (95% CI: −13.3–51.9; p=0.16) in the per-protocol population (12,452 patients).
• Vaccination did not affect the degree of viremia or the CD4+ T-cell count in patients with a subsequent diagnosis of HIV-1 infection.
• Conclusions: this vaccine regimen may reduce the risk of HIV infection in a community-based population largely at heterosexual risk of infection.
• Although providing only a modest benefit, the results are encouraging for future research
Link 26 October 2009

HIV vaccine trial results — an opening for further research.

Dolin R. N Engl J Med 2009;361 • This community-based, randomised, multicentre, double-blind, placebo-controlled trial evaluated a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) in combination with a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E).
• The study included 16,402 healthy men and women aged 18–30 years primarily at heterosexual risk for HIV infection.
• There was a trend toward the prevention of HIV-1 infection, with an efficacy of 26.4% (95% CI: −4.0–47.9; p=0.08) in the ITT population and 26.2% (95% CI: −13.3–51.9; p=0.16) in the per-protocol population (12,452 patients).
• Vaccination did not affect the degree of viremia or the CD4+ T-cell count in patients with a subsequent diagnosis of HIV-1 infection.
• Conclusions: this vaccine regimen may reduce the risk of HIV infection in a community-based population largely at heterosexual risk of infection.
• Although providing only a modest benefit, the results are encouraging for future research
Link 26 October 2009

HIV vaccine trials and tribulations.

Anon. Lancet Infect Dis 2009;9:651. • This community-based, randomised, multicentre, double-blind, placebo-controlled trial evaluated a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) in combination with a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E).
• The study included 16,402 healthy men and women aged 18–30 years primarily at heterosexual risk for HIV infection.
• There was a trend toward the prevention of HIV-1 infection, with an efficacy of 26.4% (95% CI: −4.0–47.9; p=0.08) in the ITT population and 26.2% (95% CI: −13.3–51.9; p=0.16) in the per-protocol population (12,452 patients).
• Vaccination did not affect the degree of viremia or the CD4+ T-cell count in patients with a subsequent diagnosis of HIV-1 infection.
• Conclusions: this vaccine regimen may reduce the risk of HIV infection in a community-based population largely at heterosexual risk of infection.
• Although providing only a modest benefit, the results are encouraging for future research
Link 16 November 2009

High rate of virologic suppression with raltegravir plus etravirine and darunavir/ritonavir among treatment-experienced patients infected with multidrug-resistant HIV: results of the ANRS 139 TRIO trial.

Yazdanpanah Y, Fagard C, Descamps D et al. Clin Infect Dis 2009;49:1441–9. • This phase II, non-comparative, multicentre study investigated the safety and efficacy of RAL plus ETV and DRV/r in treatment-experienced patients with multidrug-resistant HIV.
• The primary endpoint was the proportion of patients with plasma HIV RNA levels <50 copies/mL at 24 weeks.
• In addition to the investigational drugs, 90 patients (87%) received optimised background therapy that included NRTIs (86 patients) or ENF (12 patients).
• At weeks 24 and 48, 90% (95% CI: 85–96%) and 86% (95% CI: 80–93%) of patients, respectively, had an HIV RNA level <50 copies/mL. The median CD4 cell count increase was 108 cells/mm3.
• Grade 3/4 adverse events were reported in 15 patients (14.6%). Only one patient discontinued the investigational regimen because of an adverse event.
• Conclusions: The combination of RAL, ETV and DRV/r was well tolerated in treatment-experienced patients infected with multidrug-resistant virus and was associated with a rate of virologic suppression similar to that expected in treatment-naïve patients.
Link 16 November 2009

Interleukin-2 therapy in patients with HIV infection.

INSIGHT-ESPRIT Study Group, SILCAAT Scientific Committee, Abrams D et al. N Engl J Med 2009;361:1548–59. • This paper reports the results of two studies: the Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT).
• In each study, HIV+ patients with CD4 cell counts of 50–299/mm3 (SILCAAT) or ≥300/mm3 (ESPRIT) were randomly assigned to receive interleukin-2 plus ART or ART alone.
• The primary endpoint in both studies was opportunistic disease or death from any cause.
• The HRs for opportunistic disease or death from any cause with interleukin-2 plus ART (vs ART alone) were 0.91 (95% CI: 0.70–1.18; p=0.47) in the SILCAAT study and 0.94 (95% CI: 0.75–1.16; p=0.55) in ESPRIT.
• The HRs for death from any cause and for grade 4 clinical events were 1.06 (p=0.73) and 1.10 (p=0.35), respectively, in the SILCAAT study and 0.90 (p=0.42) and 1.23 (p=0.003), respectively, in ESPRIT.
• Conclusions: Despite a substantial and sustained increase in the CD4 cell count compared with ART alone, the addition of interleukin-2 showed no clinical benefit in either study.
Link 07 December 2009

Trends in multidrug treatment failure and subsequent mortality among antiretroviral therapy-experienced patients with HIV infection in North America.

Deeks SG et al. Clin Infect Dis 2009;49:1582–90. • This study used Multivariate Cox regression to assess the factors associated with time to second regimen failure and time to death after the onset of second regimen failure in patients who experienced VF (defined as an HIV RNA level >1000 copies/mL), received modified therapy and then had a second episode of VF.
• Of 42,790 patients who received therapy, 7,159 experienced a second VF. The risk of second VF decreased from 1996 (56 cases per 100 person-years) through 2005 (16 cases per 100 person-years; p<0.001). The cumulative mortality after onset of second VF was 26% at 5 years and decreased over time.
• A history of AIDS, a lower CD4+ T-cell count and a higher plasma HIV RNA level were each independently associated with mortality.
• Conclusions: Mortality rates for those who have experienced failure of two or more regimens have remained high. Plasma HIV RNA levels, CD4+ T-cell counts at time of treatment failure and a history of AIDS remain independent risk factors for death. These factors remain important targets for those in need of more aggressive therapeutic interventions.
Link 07 December 2009

Rates of virological failure in patients treated in a home-based versus a facility-based HIV-care model in Jinja, southeast Uganda: a cluster-randomised equivalence trial.

Jaffar S et al. Lancet. 2009 Nov 23. • This study investigated whether home-based HIV care was as effective as facility-based care.
• The primary endpoint was VF, defined as RNA >500 copies/mL after 6 months’ treatment.
• Of 729 home-care patients, 117 (16%) had VF versus 80 of 483 (17%) in facility care. VF rates per 100 person-years were 8.19 (95% CI: 6.84–9.82) for home and 8.67 (95% CI: 6.96–10.79) for facility care (rate ratio [RR] 1.04, 0.78–1.40; equivalence shown).
• Mortality rates were similar: 0.95 (0.71–1.28).
• Conclusions: Home-based HIV care was as effective as a clinic-based strategy and could enable improved and equitable access to HIV treatment, especially in areas with poor infrastructure and access to clinic care.
Link 07 December 2009

ART in rural Uganda—efficient scale-up with home-based care?

Korenromp EL, Viisainen KM Lancet. 2009 Nov 23. • This study investigated whether home-based HIV care was as effective as facility-based care.
• The primary endpoint was VF, defined as RNA >500 copies/mL after 6 months’ treatment.
• Of 729 home-care patients, 117 (16%) had VF versus 80 of 483 (17%) in facility care. VF rates per 100 person-years were 8.19 (95% CI: 6.84–9.82) for home and 8.67 (95% CI: 6.96–10.79) for facility care (rate ratio [RR] 1.04, 0.78–1.40; equivalence shown).
• Mortality rates were similar: 0.95 (0.71–1.28).
• Conclusions: Home-based HIV care was as effective as a clinic-based strategy and could enable improved and equitable access to HIV treatment, especially in areas with poor infrastructure and access to clinic care.
Link 18 December 2009

Rapid advice: antiretroviral therapy for HIV infection in adults and adolescents.

WHO guidelines • These three new WHO guidelines update the previous versions published in 2006.
• The guidelines aim to optimise outcomes, including QoL and survival, and to act as a reference tool for countries to adopt and adapt according to their national circumstances.
• The WHO has reviewed emerging evidence on when to initiate ART, which drug regimens to use, the management of co-infections and treatment failure, when to start and what ART to use in pregnancy, to reduce the risk of mother-to-child transmission and when breast feeding.
• The evidence was assembled following systematic reviews, GRADE profile preparation and analysis, consultations with HIV+ individuals, cost and economic impact studies, country-level feasibility assessment, and comparisons of current country guidelines.
• The aim of the guidelines is to outline standards for high-quality care by providing evidence-based recommendations, while considering the risks and benefits, acceptability, feasibility, cost and financial implications.
Link 18 December 2009

Rapid advice: use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants.

WHO guidelines • These three new WHO guidelines update the previous versions published in 2006.
• The guidelines aim to optimise outcomes, including QoL and survival, and to act as a reference tool for countries to adopt and adapt according to their national circumstances.
• The WHO has reviewed emerging evidence on when to initiate ART, which drug regimens to use, the management of co-infections and treatment failure, when to start and what ART to use in pregnancy, to reduce the risk of mother-to-child transmission and when breast feeding.
• The evidence was assembled following systematic reviews, GRADE profile preparation and analysis, consultations with HIV+ individuals, cost and economic impact studies, country-level feasibility assessment, and comparisons of current country guidelines.
• The aim of the guidelines is to outline standards for high-quality care by providing evidence-based recommendations, while considering the risks and benefits, acceptability, feasibility, cost and financial implications.
Link 18 December 2009

Rapid advice: infant feeding in the context of HIV.

WHO guidelines • These three new WHO guidelines update the previous versions published in 2006.
• The guidelines aim to optimise outcomes, including QoL and survival, and to act as a reference tool for countries to adopt and adapt according to their national circumstances.
• The WHO has reviewed emerging evidence on when to initiate ART, which drug regimens to use, the management of co-infections and treatment failure, when to start and what ART to use in pregnancy, to reduce the risk of mother-to-child transmission and when breast feeding.
• The evidence was assembled following systematic reviews, GRADE profile preparation and analysis, consultations with HIV+ individuals, cost and economic impact studies, country-level feasibility assessment, and comparisons of current country guidelines.
• The aim of the guidelines is to outline standards for high-quality care by providing evidence-based recommendations, while considering the risks and benefits, acceptability, feasibility, cost and financial implications.
Link 18 December 2009

New WHO HIV treatment and prevention guidelines.

Crowley S et al. Lancet 2009 Nov 30. • These three new WHO guidelines update the previous versions published in 2006.
• The guidelines aim to optimise outcomes, including QoL and survival, and to act as a reference tool for countries to adopt and adapt according to their national circumstances.
• The WHO has reviewed emerging evidence on when to initiate ART, which drug regimens to use, the management of co-infections and treatment failure, when to start and what ART to use in pregnancy, to reduce the risk of mother-to-child transmission and when breast feeding.
• The evidence was assembled following systematic reviews, GRADE profile preparation and analysis, consultations with HIV+ individuals, cost and economic impact studies, country-level feasibility assessment, and comparisons of current country guidelines.
• The aim of the guidelines is to outline standards for high-quality care by providing evidence-based recommendations, while considering the risks and benefits, acceptability, feasibility, cost and financial implications.
Link 11 January 2010

Suicide in HIV-Infected Individuals and the General Population in Switzerland, 1988-2008.

Keiser O et al. Am J Psychiatry [Epub ahead of print] • The study investigated time trends and predictors of suicide in the pre-HAART (1988–1995) and HAART (1996–2008) eras in HIV+ patients and the general population in Switzerland using data from the Swiss HIV Cohort Study and the Swiss National Cohort, a longitudinal mortality study in the general population.
• Standardized mortality ratios were used to compare HIV+ patients with the general population and Poisson regression was used to identify suicide risk factors.
• From 1988–2008, 150 of 15,275 patients in the Swiss HIV Cohort Study (followed for a median duration of 4.7 years) committed suicide (rate 158.4 per 100,000 person-years).
• In men, standardized mortality ratios declined from 13.7 (95% CI: 11.0–17.0) in the pre-HAART era to 3.5 (95% CI: 2.5–4.8) in the late HAART era. In women, the ratios declined from 11.6 (95% CI: 6.4–20.9) to 5.7 (95% CI: 3.2–10.3). In both periods, suicide rates tended to be higher in older patients, men, injection-drug users and patients with advanced HIV infection.
• An increase in CD4 cell counts was associated with a reduced risk of suicide.
• Conclusions: Suicide rates decreased significantly with the introduction of HAART but they remain above the rate observed in the general population and risk factors for suicide remain similar.
Link 27 January 2010

HIV-associated resources on the internet.

Armstrong WS, del Rio C. Top HIV Med 2009;17:151–62. • This review summarises high-quality HIV-related websites, including sites that provide access to HIV-related guidelines, conferences with web content, images, case studies, and clinical and scientific databases.
• It also summarises HIV-related reference and journals sites, patient information/advocacy sites and those for professional societies.
Link 27 January 2010

Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials.

Eron JJ et al. Lancet. 2010 Jan 12. • These studies compared substitution of RAL for LPV/r with continuation of LPV/r in HIV+ patients with stable viral suppression on LPV/r-based treatment.
• The primary endpoints were the mean percentage change in serum lipid concentrations from baseline to week 12; the proportion of patients with a vRNA concentration <50 copies/mL at week 24, with a prespecified non-inferiority margin of –12% for each study; and the frequency of adverse events up to 24 weeks.
• The percentage changes in lipid concentrations from baseline to week 12 were significantly greater (p<0.0001) with RAL versus LPV/r in each study.
• At week 24, 84.4% (95% CI: 80.2–88.1) of patients in the RAL group had a vRNA concentration <50 copies/mL versus 90.6% (95% CI: 87.1–93.5) of patients in the LPV/r group (treatment difference –6.2%; 95% CI : –11.2 to –1.3).
• There was no difference in the frequency of adverse events.
• The studies were terminated at week 24 because of lower than expected virological efficacy of RAL compared with LPV/r.
• Conclusion: Although switching to RAL was associated with greater reductions in serum lipid concentrations than continuation of LPV/r, RAL was not as effective as LPV/r.
Link 02 March 2010

Impact of tenofovir on renal function in HIV-infected, antiretroviral-naive patients.

Horberg M et al. J Acquir Immune Defic Syndr 2010;53:62–9. • This retrospective cohort study compared renal function among ARV-naïve patients starting a TDF-containing (964 patients) or TDF-sparing regimen (683 patients).
• Glomerular filtration rate (GFR), serum creatinine and the development of renal proximal tubular dysfunction were evaluated.
• TDF was associated with a larger relative decline in GFR over 104 weeks (–7.6 mL/min/1.73 m2 versus a TDF-sparing regimen (p< 0.001); the relative difference varied by baseline GFR, with the greatest effect seen in patients with a GFR >80 mL/min/1.73 m2.
• TDF was also associated with a higher rate of proximal tubular dysfunction over time (HR[adjusted]:1.95; p=0.01 at 52 weeks and 5.23; p=0.0004 at 104 weeks) and an increased risk of discontinuation (HR(adjusted): 1.21; p=0.02), particularly as renal function deteriorated.
• Conclusions: TDF was associated with a greater effect on renal function and a higher risk of proximal tubular dysfunction in ARV-naïve patients starting ARV treatment.
Link 02 March 2010

Substitution of nevirapine because of efavirenz toxicity in AIDS clinical trials group A5095.

Schouten JT et al. Clin Infect Dis 2010;50:787–91. • In the AIDS Clinical Trials Group study A5095, 9% of patients who experienced an EFV-related adverse event substituted NVP.
• Most adverse events resolved but 15 patients discontinued NVP.
• Grade 3/4 hepatotoxicity was observed in 14% of patients who substituted NVP versus 6% who continued EFV.
• Conclusion: Substitution of NVP because of EFV toxicity was generally safe and effective.
Link 02 March 2010

Nevirapine/zidovudine/lamivudine has superior immunological and virological responses not reflected in clinical outcomes in a 48-week randomized comparison with abacavir/ zidovudine/lamivudine in HIV-infected Ugandan adults with low CD4 cell counts.

Munderi P et al. HIV Med 2010 Feb 2. • This safety study compared NVP with ABC in ARV-naïve patients with CD4 cell counts <200 cells/mm3 in two Ugandan DART centres.
• Documented WHO stage 4 events were independently reviewed and plasma HIV-1 RNA assayed retrospectively. Exploratory efficacy analyses were ITT.
• The study drug was substituted in 7% of ABC patients vs 11% of NVP patients (p=0.09). At 48 weeks, 62% of ABC patients vs 77% of NVP patients had a VL <50 copies/mL (P<0.001) and mean CD4 cell count increases from baseline were +147 vs +173 cells/mm3, respectively (p=0.006).
• Twenty ABC patients vs 32 NVP patients developed new or recurrent WHO 4 events or died (HR: 0.60; 95% CI: 0.34–1.05; p=0.07) and 48 vs 68 developed new or recurrent WHO 3/4 events or died (HR: 0.67; 95% CI: 0.46–0.96; p=0.03).
• Conclusions: The clear virological/immunological superiority of NVP over ABC was not reflected in clinical outcomes over 48 weeks. The inability of CD4 cell count/VL to predict initial efficacy is unexplained and requires further evaluation.
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 April 2010

Late diagnosis in the HAART era: proposed common definitions and associations with mortality.

UK Collaborative HIV Cohort (UK CHIC) Steering Committee. AIDS 2010;24:723–7. • This observational cohort study attempted to define a presentation after clinical or immunological disease progression that would reliably identify patients at high risk of mortality during the first 3 months after HIV diagnosis.
• Two immunological (CD4 cell count <200 cells/mm3 and <50 cells/mm3) and two clinical (AIDS and severe/moderate AIDS) criteria for presentation with advanced HIV disease were compared.
• The predictive ability of each diagnosis for identifying individuals who died in the first 3 months after HIV diagnosis was assessed.
• Sensitivities of the individual criteria ranged from 18.0% (severe/moderate AIDS) to 50.5% (CD4 cell count <200 cells/mm3) with specificities ranging from 73.5% (CD4 <200 cells/mm3) to 97.8% (severe/moderate AIDS).
• Combinations of clinical and immunological criteria increased the sensitivity but decreased the specificity.
• Conclusion: Presentation with 'advanced HIV disease' was defined as a CD4 cell count <200 cells/mm3 or AIDS and 'late' presentation was defined as a CD4 cell count below that when treatment should be initiated (currently <350 cells/mm3) or AIDS.
Link 22 April 2010

The impact of transmitted drug-resistance on treatment selection and outcome of first-line highly active antiretroviral therapy (HAART).

Bansi L et al. J Acquir Immune Defic Syndr 2010;53:633–9. • This study investigated how resistance testing influences the outcome of first-line HAART in routine practice in the UK.
• The prevalence of transmitted drug resistance and the genotypic sensitivity score (GSS) of first-line HAART regimens were determined using data from the UK Collaborative HIV Cohort (CHIC) Study.
• Amongst patients tested from 1999–2006, 116/1175 (10%) had ≥1 resistance mutation; 64 patients (5.4%) had ≥1 mutation associated with resistance to drugs in the initial HAART regimen and 54 (4.6%) showed a GSS <3.
• Factors independently associated with a GSS <3 were starting HAART in 1999–2001 vs 2004–2006 (OR: 2.63; 95% CI: 1.19–5.83) and use of PI/r-based vs NNRTI-based regimens (OR: 1.97; 95% CI: 1.06–3.64).
• A GSS >3 was independently associated with virological suppression (HR for GSS <3: 0.60; 95% CI: 0.41–0.87).
• Conclusions: Most patients starting HAART after undergoing resistance testing received regimens with a GSS ≥3. A low GSS predicted poor virological suppression and the association persisted after adjusting for PI/r use.
Link 29 July 2010

Test and treat DC: forecasting the impact of a comprehensive HIV strategy in Washington DC.

Walensky RP et al. Clin Infect Dis 2010;51:392–400. • This study used a mathematical model of HIV case detection and treatment to evaluate combinations of HIV-screening and ART-initiation strategies.
• Current practice was defined as no regular screening program and ART at CD4 counts ≤350 cells/mm3 and test and treat was defined as annual screening and administration of ART at diagnosis.
• Outcomes included life expectancy of HIV-infected persons and changes in the population time with transmissible HIV RNA levels.
• The projected life expectancies, from an initial mean age of 41 years, are 23.9, 25.0 and 25.6 years for current practice, test and treat and test and treat with optimised ART, respectively.
• Compared with current practice, test and treat and test and treat with optimized ART would lead to a 14.7% and 27.3% reduction, respectively, in the time spent with transmissible HIV RNA level in the next 5 years.
• Conclusions: An expanded HIV test and treat programme in Washington DC would increase the life expectancy of HIV+ patients but would only have a modest impact on HIV transmission over the next 5 years that is unlikely to halt the HIV epidemic.
Link 13 August 2010

Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel.

Thompson MA, JAMA 2010;304:321–33. • Updated recommendations of the International AIDS Society-USA guidelines for the management of HIV-infected adults, using ARVs and laboratory monitoring tools available in the developed world.
• Conclusions: Patient readiness for treatment should be confirmed before initiation of ART. Treatment is recommended for asymptomatic patients with a CD4 cell count ≤500 cells/mm3, for all symptomatic patients and those with specific conditions and comorbidities.
• Treatment should be considered for asymptomatic patients with a CD4 cell count >500 cells/mm3.
• Components of the initial and subsequent regimens must be individualized, particularly in the context of concurrent conditions.
• Patients receiving ART should be regularly monitored.
• Treatment failure should be detected and managed early, with the goal of therapy, even in heavily pre-treated patients, being HIV-1 RNA suppression below commercially available assay quantification limits.
Link 13 August 2010

Early versus standard antiretroviral therapy for HIV-infected adults in Haiti.

Severe P et al. N Engl J Med 2010;363:257–65. • This randomized, open-label study compared early with standard initiation of ART in HIV+ adults in Haiti who had a confirmed CD4 cell count 200–350 cells/mm3 at baseline and no history of an AIDS illness.
• Early treatment consisted of AZT, 3TC and EFV therapy within 2 weeks of enrollment. Standard treatment used the same regimen when the CD4 cell count fell to ≤200 cells/mm3 or when clinical AIDS developed. The primary endpoint was survival.
• A total of 408 patients were enrolled in each group. There were 23 deaths in the standard- versus six in the early-treatment group (HR: 4.0; 95% CI: 1.6–9.8; p=0.001).
• Conclusions: Early initiation of ART decreased the rates of death and incident TB. Access to ART should be expanded to include all HIV+ adults with a CD4 cell count <350 cells/mm3, including those in resource-limited regions.
Link 13 August 2010

Use of generic antiretroviral agents and cost savings in PEPFAR treatment programs.

Holmes CB et al. JAMA 2010;304:313–20. • This study evaluated the uptake of generic ARVs and changes over time in ARV use and costs among PEPFAR (US President's Emergency Plan for AIDS Relief) -supported programmes in Guyana, Haiti, Vietnam and 13 countries in Africa.
• ARV expenditures increased from $116.8 million (2005) to $202.2 million (2008) and procurement increased from 6.2 million to 22.1 million monthly packs.
• The proportion spent on generic ARVs increased from 9.17% (95% CI: 9.17–9.18%) in 2005 to 76.41% (95% CI: 76.41–76.42%) in 2008 (p<0.001) and the proportion of generic packs procured increased from 14.8% (95% CI: 14.79–1.84%) in 2005 to 89.33% (95% CI: 89.32–89.34%) in 2008 (p<0.001).
• Conclusions: Among PEPFAR-supported programmes in 16 countries, the availability of generic ARVs was associated with increased ARV procurement and substantial estimated cost savings.
Link