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Treatment outcomes : Treatment outcomes

Long-term survival in HIV positive patients with up to 15 Years of antiretroviral therapy.

McManus H et al. PLoS One 2012;7(11):e48839.

• This study examined long-term survival in 2,675 HIV+ patients receiving ART in the Australian HIV Observational Database (AHOD) to describe changes in mortality versus the general population and to develop longer-term survival models. • Standardised mortality ratios (SMRs) were examined by duration of ART, CD4 and VL. Survival was analysed using Cox-proportional hazards and parametric survival models. • The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0–4.0). SMRs were 8.6 (95% CI: 7.2-10.2), 2.1 (95% CI: 1.5–2.9) and 1.5 (95% CI: 1.1–2.0) for CD4 count <350, 350–499 and ≥500 cells/mm3, respectively. • SMRs for patients with a CD4 count <350 cells/m3 were much higher than for patients with a higher CD4 count across all durations of ART. • SMRs for patients with a VL >400 copies/mL were much higher across all durations of ART. • Parametric models showed a fairly constant mortality risk by year of ART up to 15 years of treatment. • Conclusion: Observed mortality remained fairly constant by duration of ART. Mortality rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the general population.

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Editorial STRETCHing delivery of HIV health services.

Boyd M, Mohapi L. Lancet 2012 Aug 14. [Epub ahead of print].

• This study assessed the effects on mortality, viral suppression and other health outcomes and quality indicators of the Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) programme, which provides educational outreach training of nurses to initiate and re-prescribe ART and to decentralise care. • Thirty-one primary-care ART clinics were randomly assigned to implement the STRETCH programme (intervention group) or to continue with standard care (control group). • Two cohorts were enrolled: (1) adults (aged ≥16 years) with CD4 counts of ≤350 cells/μL not receiving ART and (2) adults receiving ART at enrolment and for ≥6 months. • The primary outcome was time to death in cohort 1 and the proportion of patients with an undetectable VL (<400 copies/mL) 12 months after enrolment in cohort 2. • In cohort 1, 997/4,943 patients (20%) analysed in the intervention group and 747/3,862 (19%) in the control group with known status at the end of the trial had died. The time to death was similar (HR 0.94; 95% CI: 0.76–1.15). • In cohort 2, VL suppression 12 months after enrolment was equivalent in the intervention (2,156/3,029 patients [71%]) and control (2,230/3,202 [70%]) groups (risk difference 1.1%, 95% CI: –2.4 to 4.6). • Conclusions: Expansion of the role of primary-care nurses to include ART initiation and re-prescription can be done safely and can improve health outcomes and quality of care but might not reduce the time to ART or mortality.

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Editorial. Viral load monitoring in resource-limited settings: a medical and public health priority.

Ford N et al. AIDS 2012;26:1719–20. Aug

• This analysis used a Markov model to compare the cost-effectiveness of three different strategies for long-term monitoring of ART failure and regimen switching in sub-Saharan Africa: a symptom-based approach and monitoring of either CD4 cell counts or VL.
• A symptom-based approach produced a life expectancy of 64.0 months at a total cost of US$4,028/person.
• Both laboratory-based strategies, at testing intervals of 6 or 12 months, were cost saving and improved life expectancy versus a symptom-based approach.
• The life-expectancy gain was larger for VL than CD4 count at 6- (2.3 versus 0.9 months) and 12-monthly testing (2.0 versus 0.8 months).
• Cost savings of 6-monthly VL or CD4 count were similar (US$630 versus US$621), whereas 12-monthly CD4 counts were more cost-saving than 12-monthly VL (US$1,132 versus US$880).
• Conclusion: Routine VL monitoring may be preferred as a replacement for CD4 cell counts because of its additional public-health advantages in preventing drug resistance, supporting adherence and reducing HIV transmission.

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Cost-effectiveness of laboratory monitoring for management of HIV treatment in sub-Saharan Africa: a model-based analysis.

Hamers RL et al. AIDS 2012;26:1663–1672. August

• This analysis used a Markov model to compare the cost-effectiveness of three different strategies for long-term monitoring of ART failure and regimen switching in sub-Saharan Africa: a symptom-based approach and monitoring of either CD4 cell counts or VL.
• A symptom-based approach produced a life expectancy of 64.0 months at a total cost of US$4,028/person.
• Both laboratory-based strategies, at testing intervals of 6 or 12 months, were cost saving and improved life expectancy versus a symptom-based approach.
• The life-expectancy gain was larger for VL than CD4 count at 6- (2.3 versus 0.9 months) and 12-monthly testing (2.0 versus 0.8 months).
• Cost savings of 6-monthly VL or CD4 count were similar (US$630 versus US$621), whereas 12-monthly CD4 counts were more cost-saving than 12-monthly VL (US$1,132 versus US$880).
• Conclusion: Routine VL monitoring may be preferred as a replacement for CD4 cell counts because of its additional public-health advantages in preventing drug resistance, supporting adherence and reducing HIV transmission.

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Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial.

Gibb DM et al. PLoS Med 2012 May;9(5):e1001217.

• This study investigated pregnancy outcome and maternal/infant ART in Ugandan/Zimbabwean HIV-infected women initiating ART during the DART trial. • Of 226 live births, seven (3%) infants died <2 weeks from perinatal causes and there were seven (3%) congenital abnormalities, with no effect of in utero TDF exposure (p>0.4). • Of 219 surviving infants, 182 (83%) enrolled in a follow-up study. From mothers' ART, 62/9/111 infants had no/20–89%/≥90% in utero TDF exposure; most were also exposed to AZT/3TC. • All 172 infants tested were HIV–. Overall, 14 infants died at a median age of 9 months (IQR 3–23), giving a 12-month mortality of 5%. • During follow-up, no bone fractures were reported. There was no evidence that in utero TDF affected growth after 2 years (p=0.38). • Conclusions: The 1-year infant mortality (5%) was similar to the 2–4% post-neonatal mortality observed in the region. No increase in congenital, renal or growth abnormalities was observed with in utero TDF exposure.

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The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study.

The HIV-CAUSAL Collaboration. AIDS 2012 Apr 26. [Epub ahead of print].

• This study compared regimens with EFV or NVP plus ≥2 NRTIs among HIV+, ARV-naïve and AIDS-free individuals in Europe and the United States included in the HIV-CAUSAL Collaboration. • The ITT effect for NVP versus EFV regimens on clinical, immunological and virological outcomes was estimated. The models included baseline covariates and were adjusted for potential bias introduced by censoring via inverse probability weighting. • 14,857 individuals initiated an EFV regimen (262 deaths, 744 AIDS-defining illnesses) and 7,724 a NVP regimen (196 deaths, 420 AIDS-defining illnesses). • The ITT HRs for NVP versus EFV regimens were 1.58 (95% CI: 1.26–1.97) for death and 1.26 (95% CI: 1.07–1.48) for AIDS-defining illness. • Individuals on NVP regimens experienced a smaller 12-month increase in CD4 cell count by 10.80 cells/mm and were 54% more likely to have VF at 12 months than those on EFV regimens. • Conclusions: The ITT estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count and smaller risk of VF at 12 months for EFV versus NVP.

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The cost-effectiveness of cotrimoxazole in people with advanced HIV infection initiating antiretroviral therapy in sub-Saharan Africa.

Abimbola TO, Marston BJ. J Acquir Immune Defic Syndr 2012;60:e8–14.

• This study evaluated the cost-effectiveness and possible cost savings related to prevention of specific opportunistic infections (OIs) of expanding access to cotrimoxazole (CTX) for HIV+ patients in averting mortality during the first 6 months of ART in sub-Saharan Africa. • A decision-analytic model was developed to estimate the incremental cost, deaths averted and incremental cost-effectiveness ratio. • Full coverage reduced deaths from 94 to 72 per 1000 patients, averting 22 deaths during the first 6 months of ART vs the base case. • The incremental cost of moving from base case to full coverage was estimated at $3.29 per person on ART and $146.91 per death averted over 6 months. • Additional benefits from averted OI cases would likely be realised as well as savings from averted OI treatment costs. • Conclusions: The results suggest that expanding CTX coverage is a cost-effective approach to reducing mortality among patients with advanced HIV initiating ART and may also yield benefits for OIs.

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The cost-effectiveness of preexposure prophylaxis for HIV prevention in the United States in men who have sex with men.

Juusola JL et al. Ann Intern Med 2012;156:541–50.

• Using a dynamic model of HIV transmission and progression combined with a detailed economic analysis, this study estimated the effectiveness and cost-effectiveness of PrEP in men who have sex with men (MSM) in the US. • Initiating PrEP in 20% of MSM would reduce new HIV infections by an estimated 13% and result in a gain of 550,166 QALYs over 20 years at a cost of $172,091 per QALY gained. • Initiating PrEP in a larger proportion of MSM would prevent more infections but at an increasing cost per QALY gained (up to $216,480 if all MSM receive PrEP). • PrEP in the general MSM population would cost <$100,000 per QALY gained if the daily cost of ARV drugs for PrEP was <$15 or if PrEP efficacy was >75%. • Conclusions: PrEP in the general MSM population could prevent a substantial number of HIV infections but is expensive. • PrEP in high-risk MSM compared favourably with other cost-effective interventions but could result in annual expenditures of >$4 billion.

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Expanding ART for treatment and prevention of HIV in South Africa: estimated cost and cost-effectiveness 2011–2050.

Granich R et al. PLoS One 2012;7:e30216.

• This cost-effectiveness analysis investigated the impact of expanded ART in South Africa. • A best case scenario of 90% annual HIV testing coverage in adults 15–49 years old and four ART eligibility scenarios were modelled: CD4 count <200 (current practice), <350 and <500 cells/mm3 and all CD4 levels. • Expanding ART to a CD4 count <350 cells/mm3 would prevent an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths would decline 15% from 12.5 to 10.6 million and costs drop $504 million over 5 years and $3.9 billion over 40 years with breakeven by 2013. • Expanding to ART to a CD4 count <500 cells/mm3 would prevent an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. • Expanding to all CD4 levels would decrease HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. • Conclusions: Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden.

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Efficacy and safety of rilpivirine (TMC278) versus efavirenz at 48 weeks in treatment-naïve, HIV-1-infected patients: Pooled results from the phase 3 double-blind, randomized ECHO and THRIVE trials.

Cohen C et al. J Acquir Immune Defic Syndr 2012 Feb 16. [Epub ahead of print].

• A pooled analysis of the phase III, double-blind, double-dummy ECHO and THRIVE trials comparing RPV and EFV. • Treatment-naïve, HIV-1+ adults were randomised 1:1 to RPV 25 mg qd or EFV 600 mg qd, with background TDF/FTC (ECHO) or TDF/FTC, AZT/3TC or SBC/3TC (THRIVE). • The primary endpoint was confirmed response (VL <50 copies/mm3; ITT-TLOVR algorithm) at week 48. • Confirmed responses were RPV 84% and EFV 82%. The difference in response rates was 2.0% (95% CI: –2.0–6.0%). • The incidence of VF was 9% RPV vs 5% EFV. • Responses were similar for RPV and EFV by background regimen, gender, race and clade. • RPV vs EFV had a smaller incidence of AEs leading to discontinuation (3% vs 8%), treatment-related grade 2–4 AEs (16% vs 31%), rash (3% vs 14%), dizziness (8% vs 26%), abnormal dreams/nightmares (8% vs 13%) and grade 2–4 lipid abnormalities. • Conclusions: At week 48, RPV 25 mg qd and EFV 600 mg qd had comparable response rates. RPV had more VFs and improved tolerability vs EFV.

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Impact of late diagnosis and treatment on life expectancy in people with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study.

May M et al. BMJ 2011;343:d6016.

• This study estimated life expectancy in HIV+ patients receiving treatment versus that in the general population and assessed the impact of late treatment (defined as a CD4 count <200 cells/mm3 at the start of ART). • The main outcome measure was life expectancy at the exact age of 20 years (the average additional years that will be lived by a person after age 20), according to the cross-sectional, age-specific mortality rates during the study period (1996–2008). • Life expectancy (SE) increased from 30.0 (1.2) to 45.8 (1.7) years from 1996–9 to 2006–8 and was 39.5 (0.45) for male and 50.2 (0.45) years for female patients versus 57.8 and 61.6 years for men and women in the general population (1996–2006). • Delaying ART resulted in up to 15 years’ loss of life: life expectancy was 37.9 (1.3), 41.0 (2.2) and 53.4 (1.2) years in those starting ART with a CD4 count of <100, 100–199 and 200–350 cells/mm3, respectively. • Conclusions: Life expectancy in HIV+ patients has increased by >15 years from 1996–2008 but is still about 13 years less than that of the general population. Earlier diagnosis and ART treatment may increase life expectancy.

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Editorial Optimizing initial therapy for HIV infection.

Hull MW, Montaner JS. J Infect Dis 2011;204:1154–6. Oct

• The AIDS Clinical Trials Group A5202 study compared blinded ABC/3TC to TDF/FTC with EFV or ATV/r in HIV+ treatment-naïve patients, stratified by screening HIV RNA (< or ≥105 copies/mL). Due to higher VF with ABC/3TC in the high HIV RNA stratum, blinded treatment was stopped in this group but follow-up continued for all patients. • In the low stratum, time to VF was similar for ABC/3TC and TDF/FTC with ATV/r (HR]: 1.25; 95% CI: 0.76–2.05) or EFV (HR: 1.23; 95% CI: 0.77–1.96), with significantly shorter times to regimen modification for ABC/3TC with EFV or ATV/r and to safety events with EFV. • In the high stratum prior to stopping blinded treatment, higher VF rates were seen for ABC/3TC with EFV (HR: 2.46; 95% CI: 1.20–5.05) or ATV/r (HR: 2.22; 95% CI: 1.19–4.14). • Conclusions: In the low HIV RNA stratum, time to VF with ABC/3TC or TDF/FTC was similar for EFV and ATV/r. In the high stratum, the VF rate was significantly higher for ABC/3TC versus TDF/FTC with either EFV or ATV/r.

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Abacavir/lamivudine versus tenofovir DF/emtricitabine as part of combination regimens for initial treatment of HIV: final results.

Sax PE et al. J Infect Dis 2011;204:1191–201. Oct

• The AIDS Clinical Trials Group A5202 study compared blinded ABC/3TC to TDF/FTC with EFV or ATV/r in HIV+ treatment-naïve patients, stratified by screening HIV RNA (< or ≥105 copies/mL). Due to higher VF with ABC/3TC in the high HIV RNA stratum, blinded treatment was stopped in this group but follow-up continued for all patients. • In the low stratum, time to VF was similar for ABC/3TC and TDF/FTC with ATV/r (HR]: 1.25; 95% CI: 0.76–2.05) or EFV (HR: 1.23; 95% CI: 0.77–1.96), with significantly shorter times to regimen modification for ABC/3TC with EFV or ATV/r and to safety events with EFV. • In the high stratum prior to stopping blinded treatment, higher VF rates were seen for ABC/3TC with EFV (HR: 2.46; 95% CI: 1.20–5.05) or ATV/r (HR: 2.22; 95% CI: 1.19–4.14). • Conclusions: In the low HIV RNA stratum, time to VF with ABC/3TC or TDF/FTC was similar for EFV and ATV/r. In the high stratum, the VF rate was significantly higher for ABC/3TC versus TDF/FTC with either EFV or ATV/r.

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Editorial: Antiretroviral therapy: now "it just works".

Sax PE. Clin Infect Dis 2011;53:605–8.

• This study investigated the trend in HIV-1 RNA levels over time in HIV+ patients in a large urban HIV clinical practice in Baltimore, Maryland.
• From 1996 (shortly after HAART was introduced) to 2010, the median HIV-1 RNA level decreased from 10, 400 to <200 copies/mL and the proportion of patients with an HIV-1 RNA level >500 copies/mL decreased from 75% to 16%.
• Conclusions: the results demonstrate the remarkable impact of increased use of and improved management with HAART.

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Dramatic decline in the HIV-1 RNA level over calendar time in a large urban HIV practice.

Moore RD, Bartlett JG. Clin Infect Dis 2011;53:600–4.

• This study investigated the trend in HIV-1 RNA levels over time in HIV+ patients in a large urban HIV clinical practice in Baltimore, Maryland.
• From 1996 (shortly after HAART was introduced) to 2010, the median HIV-1 RNA level decreased from 10, 400 to <200 copies/mL and the proportion of patients with an HIV-1 RNA level >500 copies/mL decreased from 75% to 16%.
• Conclusions: the results demonstrate the remarkable impact of increased use of and improved management with HAART.

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Economic evaluation of monitoring virologic responses to antiretroviral therapy in HIV-infected children in resource-limited settings.

Schneider K et al. AIDS 2011;25:1143–51.

• This study investigated the cost effectiveness and cost utility of different frequencies of plasma VL monitoring in HIV+ children initiating ART in a resource-limited setting (Thailand) using a stochastic agent-based simulation model.
• The model simulated the expected costs and clinical outcomes over time according to different VL monitoring frequencies and initiation of second-line therapies.
• After screening at 6 months, the optimal VL monitoring frequency was annual. Associated costs of VL monitoring and appropriate ART would approximately triple current treatment costs.
• Compared with current practice, a single screening during the first year of ART led to a 58.4% reduction in the total person-years of VF, with annual monitoring leading to a 76.6% reduction.
• The estimated cost of preventing 1 year of VF was US$3,393 with and US$359 without ART costs.
• Conclusions: VL monitoring is cost-effective in many resource-limited settings.

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Evidence for the cure of HIV infection by CCR5{Delta}32/{Delta}32 stem cell transplantation.

Allers K et al. Blood 2011;117:2791–9. March

• This article reports the possible cure of HIV in a patient after transplantation with CCR5Δ32/Δ32 stem cells.
• CD4+ T cells were successfully reconstituted at the systemic level as well as in the gut mucosal immune system following CCR5Δ32/Δ32 stem cell transplantation and the patient remains without any sign of HIV infection.
• During immune reconstitution, there was evidence for the replacement of long-lived host tissue cells with donor-derived cells, indicating that the size of the viral reservoir was reduced over time.
• Conclusions: The results strongly suggest that cure of HIV was achieved in this patient.

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The DART Trial: ‘The Doctor's Dilemma’ revisited

Nunes EP et al J Antimicrob Chemother; First published online 15 February 2011 doi:10.1093/jac/dkr020

• This is a Leading Article commenting on the results of the DART trial.
• Although antiretroviral drugs are now more accessible in developing countries, and adherence to therapy is good, there remain questions regarding the need for routine laboratory monitoring given the scarce laboratory resources available. .
• DART was a randomised controlled trial carried out in Uganda and Zimbabwe in 2003–2008, and evaluated differences in efficacy and safety outcomes in patients receiving routine laboratory monitoring vs monitoring driven by clinical events.
• The results of DART suggest that in resource constrained settings, clinically driven monitoring is the more cost-effective solution.

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Dose optimisation: a strategy to improve tolerability and lower antiretroviral drug prices in low and middle income countries

Hill A et al Open Infect Dis J; 2010;4:85–91

• This article reviews dose optimisation as a means of increasing access to antiretrovirals for HIV-infected people in low and middle income countries.
• 5 million people in these countries are eligible for treatment but are not receiving it; furthermore, 27–29 million infected people are currently not receiving treatment butwill eventually require it as their disease progresses. The overall costs of treatment programs needs to be reduced to allow for greater access to treatment.
• Several doses of new antiretrovirals are usually evaluated in dose-ranging studies. With efavirenz, lopinavir/ritonavir and raltegravir, although there was no difference in efficacy between several doses tested in phase 2 studies, it was the higher doses that were evaluated in phase 3 studies and approved for clinical use.
• Reanalysis of the dose-ranging trials shows that the effective doses of these drugs could be lowered significantly, thereby allowing wider first- and second-line use in low- and middle income countries, by reducing the costs of these drugs by around 30–35%.

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First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial

The PENPACT-1 (PENTA 9/PACTG 390) Study Team Lancet Infect Dis, 2011 Feb 01 [Epub ahead of print]

• This article reports a randomised open-label study (PENPACT-1) comparing NNRTI- and PI-based treatment in previously untreated children.
• 266 children were randomised to receive two NRTIs plus an NNRTI or PI, and then to switch to second-line treatment at viral-load thresholds of either 1000 or 30,000 copies/mL. Median follow-up was 5.0 years.
• At 4 years, mean reductions in viral load were –3.16 log10copies/mL for PIs vs –3.31 log10copies/mL for NNRTIs (p=0.26); and –3.26 vs –3.20 log10copies/mL (p=0.56) for switching at the low vs high thresholds, respectively.
• PI resistance was uncommon and there was no difference in NRTI resistance between the low vs high switch groups. NNRTI resistance was selected early, and NRTI resistance was 10% higher when switched at the high vs the low threshold.
• It was concluded that all the treatment regimens provided good long-term outcomes. Delayed switch from PI-based ART may be reasonable if future drug options are limited, but early switch from first-line NNRTI-based therapy is required in the event of failure.

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High dose atorvastatin decreases cellular markers of immune activation without affecting HIV-1 RNA levels: results of a double-blind randomized placebo controlled clinical trial

Ganesan A et al J Infect Dis, 2011;203:756–64

• This report describes a randomised, double-blind placebo-controlled crossover trial studying the antiviral activity of atorvastatin on HIV-1 RNA and cellular markers of immune activation.
• 24 HIV-infected individuals, not receiving anti-retroviral therapy, were randomised to either 8 weeks’ atorvastatin 80 mg or placebo daily, with crossover after 4–6 weeks’ washout.
• Atorvastatin therapy had no effect on HIV-1 RNA levels, but cellular markers of immune activation were reduced. Circulating proportions of CD4+ HLA-DR+, CD8+ HLA-DR+ and CD8+ HLA-DR+ CD38+ T cells were reduced by 2.5% (p=0.02), 5% (p=0.006) and 3% (p=0.03), respectively, vs placebo.
• Conclusions: The proportion of activated T lymphocytes fell modestly but significantly following short-term administration of atorvastatin.

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Statins as anti-inflammatory therapy in HIV disease

Carr A J Infect Dis 2011;203:751–2

• This Editorial reviews the potential use of statins as anti-inflammatory and antiretroviral treatment, with a focus on the paper by Ganesan et al in the same issue of the journal (J Infect Dis 2011;203:756–64).
• In addition to their lipid-lowering effect, statins reduce plasma levels of C-reactive protein and have several cellular immunological effects. Some studies have shown that statins inhibit HIV replication in vitro, though the mechanism for this is unclear.
• Ganesan et al found significant reductions in cellular markers of immune activation on T-lymphocytes in untreated HIV-infected individuals receiving high-dose atorvastatin. While T-lymphocyte activation is associated with more rapid HIV disease progression, the magnitude of reduction required to affect a clinically relevant difference is unknown.
• A large, longer-term study would be worthwhile, evaluating the effect of statins on inflammatory biomarkers and whether this translates into reduced HIV disease progression and fewer cases of inflammatory non-AIDS related outcomes, such as cardiovascular disease and end-organ damage.

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Triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora study): a randomised controlled trial.

The Kesho Bora Study Group. Lancet Infect Dis 2011 Jan 13 [Epub ahead of print].

• This open-label study investigated the efficacy and safety of triple ART (AZT+3TC+LPV/r) vs AZT plus single-dose NVP prophylaxis in pregnant women infected with HIV at five sites in Burkina Faso, Kenya and South Africa.
• The primary endpoints were HIV-free infant survival at 6 weeks and 12 months, HIV-free survival at 12 months in infants who were ever breastfed, AIDS-free survival in mothers at 18 months and serious adverse events in mothers and babies.
• From June 2005 to August 2008, 882 women were enrolled, 824 of whom were randomised and gave birth to 805 singleton or first, live-born infants.
• The cumulative rate of HIV transmission at 6 weeks and 12 months was 3.3% (95% CI: 1.9–5.6%) and 5.4% (95% CI: 3.6–8.1%) with triple ART vs 5.0% (95% CI: 3.3–7.7%) and 9.5% (95% CI: 7.0–12.9%) with AZT plus single-dose NVP (p=0•029).
• The cumulative rate of HIV transmission or death at 12 months was 10.2% (95% CI: 7.6–13.6%) with triple ART vs 16.0% (95% CI: 12.7–20.0%) with AZT plus single-dose NVP (p=0•017). In infants whose mothers declared they intended to breastfeed, the cumulative rate of HIV transmission at 12 months was 5.6% (95% CI: 3.4–8.9%) vs 10.7% (95% CI: 7.6–14.8%), respectively (p=0•02).
• The incidence of serious adverse events in both mothers and infants was similar in both groups.
• Conclusions: Triple ART prophylaxis during pregnancy and breastfeeding was safe and reduced the risk of HIV transmission.

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Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation.

Allers K et al. Blood 2010 Dec 8

• Key changes made to update the December 1 2009 guidelines include the sections on CD4 T-cell counts, VL and drug-resistance testing, initial combination regimens for ARV-naïve patients, HBV/HIV and TB/HIV co-infection and adverse events.
• This article reports the possible cure of HIV in a patient after transplantation with CCR5Δ32/Δ32 stem cells.
• CD4+ T cells were successfully reconstituted at the systemic level as well as in the gut mucosal immune system following CCR5Δ32/Δ32 stem cell transplantation and the patient remains without any sign of HIV infection.
• During immune reconstitution, there was evidence for the replacement of long-lived host tissue cells with donor-derived cells, indicating that the size of the viral reservoir was reduced over time.
• Conclusions: The results strongly suggest that cure of HIV was achieved in this patient.

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Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study.

Lubomirov R et al. J Infect Dis 2011;203:246–257

• This study investigated the association of pharmacogenetic markers with time to treatment discontinuation during the first year of ART in 577 treatment-naïve patients initiating TDF (n=500) or ABC (n=77) with EFV (n=272), LPV/r (n=184) or ATV/r (n=121).
• During the first year of ART, 190 patients (33%) stopped ≥1 drugs. For EFV and ATV, patients with genetic risk markers vs those without experienced higher discontinuation rates (71.15% vs 28.10% and 62.5% vs 14.6%, respectively).
• The discontinuation HRs were 3.14 (95% CI: 1.35–7.33; p=0.008) for EFV and 9.13 (95% CI: 3.38–24.69; p<0.0001) for ATV.
• Conclusions. Several pharmacogenetic markers identified patients at risk for early treatment discontinuation. These should be validated in the clinical setting.

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The cost-effectiveness and population outcomes of expanded HIV screening and antiretroviral treatment in the United States.

Long EF et al. Ann Intern Med 2010;153:778–89.

• This study used a dynamic mathematical model of HIV transmission and disease progression and cost-effectiveness analysis to evaluate the effects of expanded ART, HIV screening and interventions to reduce risk behaviour on the HIV epidemic in the US.
• One-time HIV screening of low-risk individuals plus annual screening of high-risk individuals was shown to prevent 6.7% of a projected 1.23 million new infections and cost $22,382 per QALY gained, assuming a 20% reduction in sexual activity after screening. Expanding ART to 75% of eligible individuals was shown to prevent 10.3% of infections and cost $20,300 per QALY gained. A combination strategy could prevent 17.3% of infections and costs $21,580 per QALY gained.
• With no reduction in sexual activity, expanded screening could prevent 3.7% of infections. Earlier ART initiation at a CD4 cell count of >350 cells/mm3 could prevent 20–28% of infections. Additional efforts to halve high-risk behaviour could reduce infections by 65%.
• Conclusions: Simultaneous expansion of HIV screening and treatment is cost effective and provides the greatest health benefit. However, this is not sufficient to significantly reduce the HIV epidemic in the US without a substantial decrease in risk behaviour.

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Higher efficacy of nevirapine than efavirenz to achieve HIV-1 plasma viral load below 1 copy/ml.

Haïm-Boukobza S et al. AIDS 2010 Dec 13

• This study compared the level of HIV-1 residual viraemia (VL <50 copies/mL) in 165 patients receiving a TDF/FTC and NVP (n=75) or EFV (n=90)-containing regimen.
• A greater percentage of NVP vs EFV patients had a VL <50 copies/mL (81.3% vs 55.6%; p<0.001). In a multivariate analysis, only NVP vs EFV (p=0.005) and duration of viral suppression with ART (p=0.005) were independently associated with a VL <50 copies/mL.
• Conclusions: The good penetration of NVP could explain the control of viral replication in some anatomic compartments and thus the reduction in VL.

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A single tablet regimen is associated with higher adherence and viral suppression than multiple tablet regimens in HIV+ homeless and marginally housed people.

Bangsberg DR et al. AIDS 2010;24:2835–40

• This study assessed adherence and virological response to Atripla among a cohort of homeless and marginally housed individuals and compared the results with historical controls followed in the same cohort.
• Adherence was higher with Atripla versus multiple-pill, once-daily therapy (p=0.006) after controlling for multiple confounders.
• Viral suppression (VL <50 copies/mL) was also greater with Atripla (69.2% versus 46.5%; p=0.02) but there was no difference in viral suppression after controlling for adherence.
• Conclusion: Once-daily Atripla appears to be a reasonable option for individuals with multiple barriers to adherence.

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Difference in absolute CD4+ count according to CD4 percentage between Asian and Caucasian HIV-infected patients.

Achhra AC et al. J AIDS Clinic Res 2010;1:101.

This study compared the absolute CD4+ cell count at different CD4+ percentages between untreated Asian (n=442) and Caucasian (n=674) HIV+ individuals, using linear regression methods.
For any given CD4 percentage, Asian patients had a lower CD4+ cell count than Caucasians (p=0.001). The difference varied from 38.9 cells/mm3 (95% CI: 3.3–74.5) at a CD4 percentage of 15% to 108.7 cells/mm3 (95% CI: 42.5–174.9) at 40%.
Conclusions: The impact of these differences on prognosis is unclear but prognostic thresholds for CD4+ cell counts used in Caucasians may be inappropriate in Asian populations

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Outcomes of patients on dual-boosted PI regimens: experience of the Swiss HIV Cohort Study.

Osih RB et al. AIDS Res Hum Retroviruses

This study investigated viral suppression at 24 weeks in patients receiving a dual-boosted PI regimen between January1996 and March 2007 in the Swiss HIV Cohort Study.
A total of 295 patients (72.5%) received a dual-boosted PI regimen for >6 months (median duration 2.2 years).
Of 287 patients who had a VL >400 copies/mL at the beginning of ART, 184 (64.1%) were ever suppressed and 156 (54.4%) were suppressed within 24 weeks. The median time to suppression was 101 days (95% CI: 90–125).
The median number of previous regimens was 6 (range, 3–8).
Acquisition of HIV through intravenous drug use and the use of LPV + SQV or ATV were associated with an increased likelihood of suppression within 6 months.
Conclusions: Patients on a dual-boosted PI regimen were heavily treatment experienced. Viral suppression within 6 months was achieved in >50% of patients.

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Evidence of persistent low level viraemia in long-term HAART suppressed, HIV infected individuals

Hatano H AIDS 2010;24:2535–9

This study investigated the extent to which residual low-level viraemia persists during long-term ART.
The study included 180 HIV+ patients (median duration of HIV infection 12 years) who had at least two consecutive plasma VL levels below the level of detection (<50–75 copies/mL) while taking ART; 36 patients had been virologically suppressed for >5 years. Longitudinal plasma samples taken during periods of VL suppression were analysed.
In the first year of viral suppression, VL declined significantly (p=0.001) but there was no evidence for a continued decline after 12 months (p=0.383). Similarly, HIV antibody levels also declined (p=0.054) but there was no evidence for a continued decline after 12 months (p=0.988).
Conclusions: Viraemia and the HIV-associated host response appear to achieve a steady-state level during long-term combination ART.

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Virologic and immunologic response to HAART, by age and regimen class.

Althoff KN et al. AIDS 2010;24:2469–79.

• This pooled analysis investigated the impact of age and initial HAART regimen class on virological and immunological response within 2 years of starting therapy.
• Of 12,196 eligible patients (mean age 42 years), 57% initiated a PI-based and 48% an NNRTI-based regimen and 50% changed regimen class after initiation.
• A virological response was less likely in patients starting with a boosted-PI regimen (adjusted hazard odds ratios (aHOR): 0.77; 95% CI: 0.73–0.82), irrespective of age.
• The immunological response decreased with increasing age (18–<30 years, ref; 30–<40 years, aHOR: 0.92; 95% CI: 0.85–1.00; 40–<50 years, aHOR: 0.85 ;95% CI: 0.78–0.92; 50–<60 years, aHOR: 0.82; 95% CI: 0.74–0.90; ≥60 years, aHOR: 0.74; 95% CI: 0.65–0.85), irrespective of the initial regimen.
• Conclusions: There was no evidence of an interaction between age or initial HAART regimen and virological or immunological response. However, a decreased immunological response with increasing age may have implications for age-specific guidelines on when to start treatment.

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The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: a randomized controlled trial.

Gandhi R et al. PLoS Med. 2010 Aug 10;7(8). pii: e1000321.

• This double-blind study investigated whether adding RAL lowered the level of residual viremia in 53 HIV-1+ patients on effective ART with plasma HIV-1 RNA levels below the detection limits of commercial assays.
• Patients receiving ART who had plasma HIV-1 RNA levels <50 copies/mL but detectable viremia by single copy assay (SCA) were randomized to the addition of either RAL or placebo for 12 weeks then crossed over for another 12 weeks. The primary endpoint was the plasma HIV-1 RNA by SCA averaged between weeks 10 and 12 compared between treatment groups.
• The HIV-1 RNA level did not differ significantly between the RAL (n=25) and placebo (n=24) groups (median 1.2 versus 1.7 copies/Ml; p=0.55), nor did the change in HIV-1 RNA level from baseline (median –0.2 and –0.1 copies/mL; p=0.71). There was also no significant change in HIV-1 RNA level after patients crossed over.
• Conclusions: RAL intensification did not reduce low-level plasma viraemia in patients on effective ART, suggesting that residual viremia does not arise from ongoing HIV-1 replication and infection of new cells.

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Prognosis of patients with HIV-1 infection starting antiretroviral therapy in sub-Saharan Africa: a collaborative analysis of scale-up programmes.

May M et al. Lancet 2010;376:449–57.

• This study provides two prognostic models to estimate the probability of death in patients starting ART in sub-Saharan Africa.
• Weibull survival models were used to construct two prognostic models: one with CD4 cell count, clinical stage, bodyweight, age and sex (CD4 count model) and one that replaced CD4 cell count with total lymphocyte count and severity of anaemia (total lymphocyte and haemoglobin model) as CD4 cell count is not routinely measured in many African ART programmes. The primary outcome was all-cause mortality in the first year of ART.
• Mortality was strongly associated with high baseline CD4 cell count (≥200 versus <25 cells/mm3; adjusted HR: 0.21; 95% CI: 0.17–0.27), WHO clinical stage (stages III/IV versus I/II; adjusted HR 3.45; 95% CI: 2.43–4.90), bodyweight (≥60 versus <45 kg; adjusted HR 0.23; 95% CI: 0.18–0.30) and anaemia status (none versus severe: HR: 0.27; 95% CI: 0.20–0.36). Other independent mortality risk factors were low total lymphocyte count, advanced age and male sex.
• The probability of death at 1 year ranged from 0.9% (95% CI: 0.6–1.4) to 52.5% (43.8–61.7) with the CD4 count model and from 0.9% (0.5–1.4) to 59.6% (48.2–71.4) with the total lymphocyte and haemoglobin model. Both models accurately predicted early mortality.
• Conclusions: Prognostic models should be used to counsel patients, plan health services and predict outcomes for patients with HIV-1 infection in sub-Saharan Africa.

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Comparative effectiveness of HIV testing and treatment in highly endemic regions.

Bendavid E et al. Arch Intern Med 2010;170:1347–54.

• This study simulated the HIV epidemic and disease progression in South Africa to compare the outcomes of the current HIV treatment campaign with four test and treat strategies to increase ART access: 1 universal test and treat without changes in linkage to care and loss to follow up; 2 universal test and treat with improved linkage to care; 3 universal test and treat with reduced loss to follow up and 4 comprehensive care with universal test and treat, improved linkage to care, and reduced loss to follow up.
• The main outcome measures were survival benefits, new HIV infections and HIV prevalence.
• Compared with the present strategy, 1 was associated with a mean (95% uncertainty bounds) life expectancy gain of 12.0 months (11.3–12.2 months), and 35.3% (32.7–37.5%) fewer HIV infections over 10 years. Substantial additional benefits were provided by 2, 3 and 4: life expectancy gains versus the current strategy were 16.1, 18.6, and 22.2 months and new infections were 55.5%, 51.4% and 73.2% lower, respectively.
• Conclusions: A universal test and treat strategy with the current levels of linkage to care and loss to follow up could substantially reduce HIV mortality and new infections. Increasing linkage to care and preventing loss to follow up provides nearly twice the benefits of universal test and treat alone.

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Rate of CD4+ cell count increase over periods of viral load suppression: relationship with the number of previous virological failures.

Trotta MP et al. Clin Infect Dis 2010;51:456–64.

• This study analysed patients with ≥1 episode of viral suppression after starting first-line ART (n=3,537) from the ICONA Foundation study.
• The percentage of patients with an increase in CD4 cell count >300 cells/mm3 and the rate of CD4 cell count increase per year were estimated.
• The median time to reach a CD4 cell count increase >300 cells/mm3 was significantly associated with the number of failed regimens: 34, 41, 51 and 45 months in patients without evidence of previous virological failure and 1, 2 or ≥3 previous virological failures, respectively (p<0.001). The annual estimated increases in CD4 cell count were 36, 28, 31 and 26 cells/mm3, respectively.
• Conclusions: Patients with ≥1 virological failure took a longer time to reach a CD4 cell count >300 cell/mm3 and had a slower annual increase than those without virological failure.
• First-line ART should be optimised to provide the best chance of achieving an effective CD4 cell response.

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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.

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Comparison of 2 doses of liposomal amphotericin B and conventional amphotericin B deoxycholate for treatment of AIDS-associated acute cryptococcal meningitis: a randomized, double-blind clinical trial of efficacy and safety.

Hamill RJ et al. Clin Infect Dis 2010;51:225–32.

• This study compared the efficacy and safety of liposomal amphotericin B (3 or 6mg/kg/day) with that of conventional amphotericin deoxycholate in patients with AIDS and acute cryptococcal meningitis.
• Efficacy was similar for all three treatments.
• The overall incidence of infusion-related reactions was significantly lower for both liposomal doses compared with conventional amphotericin B (p<0.001).
• The 3 mg/kg/day liposomal amphotericin B dose was associated with significantly less nephrotoxicity than conventional amphotericin B (p=0.004).
• Conclusions: Liposomal amphotericin B provides an equally effective alternative to conventional amphotericin B deoxycholate in patients with AIDS and acute cryptococcal meningitis.

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Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review.

Barth RE et al. Lancet Infect Dis 2010;10:155–66.

• This article reviews the virological efficacy and drug-resistance outcomes of 89 ART studies in sub-Saharan Africa.
• In an on-treatment analysis, 10,351 (78%) of 13,288 patients showed virological suppression after 6 months of ART, 7413 (76%) of 9,794 after 12 months and 3,840 (67%) of 5,690 after 24 months.
• Resistance profiles were associated with commonly used ARVs: the lamivudine-associated M184V mutation was most frequent, followed by the NNRTI-associated K103N mutation. Thymidine-analogue mutations and the K65R mutation were less frequent.
• Conclusions: First-line ART regimens used in sub-Saharan Africa were effective. Drug-resistance profiles suggest that a PI-based regimen with a NRTI backbone is a reasonable second-line option.

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Pretreatment CD4 cell slope and progression to AIDS or death in HIV-infected patients initiating antiretroviral therapy--the CASCADE collaboration: a collaboration of 23 cohort studies.

Wolbers M et al. PLoS Med 2010;7:e1000239.

• This survival analysis of patients from 23 cohorts of the CASCADE study investigated whether the rate of CD4 cell decline prior to ART is related to prognosis and should affect when ART is started.
• A pre-ART CD4 slope was estimated using a linear mixed effects model for each patient. The primary outcome was the time from starting ART to the first new AIDS event or death.
• The HR for AIDS or death was 1.01 (95% CI: 0.97–1.04) for each 10 cells/mm3 per year reduction in pre-ART CD4 cell decline.
• There was no association between pre-ART CD4 cell slope and survival.
• Conclusions: The CD4 cell slope did not improve the prediction of clinical outcome in patients with a CD4 cell count >350 cells/mm3.

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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.

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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.

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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.

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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.

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The risk of virologic failure decreases with duration of HIV suppression, at greater than 50% adherence to antiretroviral therapy

Rosenblum M, Deeks SG, van der Laan M et al. PLoS One 2009;4:e7196.

• This study investigated the hypothesis that the percentage adherence to ART necessary to maintain HIV suppression would decrease the longer the duration of viral suppression.
• Adherence to ART was measured through pill counts. The effect of adherence to ART on the probability of VF during early and late viral suppression was determined.
• Comparing the probability of VF just after achieving viral suppression vs after 12 consecutive months of suppression, there was a statistically significant decrease in the probability of VF for each range of adherence proportions considered, as long as adherence was >50%.
• The estimated risk difference, comparing the probability of VF after 1 month vs after 12 months of continuous viral suppression was 0.47 (95% CI: 0.23–0.63) at 50–74% adherence, 0.29 (95% CI: 0.03–0.50) at 75–89% adherence and 0.36 (95% CI: 0.23–0.48) at 90–100% adherence.
• Conclusions: The risk of VF for adherence >50% declined with a longer duration of continuous viral suppression.

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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.

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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.

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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.

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Slow accumulation of HIV resistance mutations: implications for resource-limited settings?

Stevens WS. J Infect Dis 2009;200:670–2.

• This study investigated the effect of continuing virologically failing ART in resource-limited settings in terms of the rate of accumulation of thymidine analogue mutations (TAMs).
• The study included patients in EuroSIDA with two genotypic resistance tests ([HIV RNA >500 copies/mL in any measure between tests, the first being performed after the first VF of a TA, which was continued until the second test.
• At the first test, 1 year after VF, a median of three TAMs were detected. Overall, 126 TAMs were accumulated during 548 person-years of follow-up (1/4.3 years; 95%CI: 3.7–5.0 years).
• Greater predicted activity of the TA at t0, TAM profile 2 (versus TAM profile 1) at t0, use of a NNRTI at t0 (versus combined NNRTI and PI), and heterosexual acquisition of HIV (versus homosexual) were associated with a faster rate of TAM accumulation.
• Conclusions: Although the estimated rate of TAM accumulation was lower than anticipated, all possible efforts should be continued to increase the availability of drug options in resource-limited settings.

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Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings.

Cozzi-Lepri A, Phillips AN, Martinez-Picado J et al. J Infect Dis 2009;200:687–97.

• This study investigated the effect of continuing virologically failing ART in resource-limited settings in terms of the rate of accumulation of thymidine analogue mutations (TAMs).
• The study included patients in EuroSIDA with two genotypic resistance tests ([HIV RNA >500 copies/mL in any measure between tests, the first being performed after the first VF of a TA, which was continued until the second test.
• At the first test, 1 year after VF, a median of three TAMs were detected. Overall, 126 TAMs were accumulated during 548 person-years of follow-up (1/4.3 years; 95%CI: 3.7–5.0 years).
• Greater predicted activity of the TA at t0, TAM profile 2 (versus TAM profile 1) at t0, use of a NNRTI at t0 (versus combined NNRTI and PI), and heterosexual acquisition of HIV (versus homosexual) were associated with a faster rate of TAM accumulation.
• Conclusions: Although the estimated rate of TAM accumulation was lower than anticipated, all possible efforts should be continued to increase the availability of drug options in resource-limited settings.

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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.

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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.

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Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance.

Marra CM, Zhao Y, Clifford DB et al. AIDS 2009;23:1359–66.

• This study investigated whether ARV regimens with good CNS penetration control HIV in the CSF by measuring the concentration of HIV RNA in CSF and blood and improve cognition by measuring neuropsychological test scores (NPZ4 and NPZ8).
• ARV regimens were graded by CNS penetration effectiveness (CPE) rank (≥2 or <2).
• The odds of suppression of CSF HIV RNA were higher with a CPE rank ≥2 than <2.
• The odds of suppression of plasma HIV RNA were not associated with CPE rank.
• Patients with impaired neuropsychological performance who received regimens with a CPE rank of ≥2 had lower composite NPZ4 scores over the course of the study.
• Conclusions: ARV regimens with good CNS penetration were more effective in controlling CSF viral replication than those with poorer penetration. ARV regimens with good CNS penetration were associated with poorer neurocognitive performance.

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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, Wester CW, Thomas A et al. J Acquir Immune Defic Syndr. 2009;51:37–46.

• The Tshepo study compared the efficacy and tolerability of three NRTI combinations (ZDV+3TC, ZDV+ddI and d4T+3TC) and two different NNRTIs (NVP and EFV) and two different adherence strategies (the current standard of care and an ‘intensified adherence strategy).
• The ZDV+ddI arms were discontinued due to inferiority in the primary endpoint (VF with resistance).
• VF and genotypic resistance mutations occurred in 11% of patients receiving ZDV+ddI-based ART versus 2% in patients receiving either ZDV+3TC- or d4T+3TC-based ART (p=0.002).
• The median CD4-cell count increase at 1 and 2 years was 137 and 199 cells/mm3 and the percentage of patients with plasma HIV-1 RNA level ≤400 copies/mL was 92.0% and 88.8%.
• Kaplan–Meier survival estimates at 1 and 2 years were 96.6% and 95.4%. One hundred and twenty patients (18.2%) had treatment-modifying toxicities: the most common were lipodystrophy, anaemia, neutropenia, and Stevens–Johnson syndrome.
• Conclusions: The preliminary results show overall excellent efficacy and tolerability of NNRTI-based ART among HIV-1 subtype C–infected adults. However, ZDV+ddI is inferior to d4T+3TC or ZDV+3TC when used with an NNRTI for first-line ART.

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Monitoring HIV treatment in resource‐limited settings: reassuring news on the usefulness of CD4+ cell counts.

Fowler MG, Owor M. J Infect Dis 2009;199:1255–7.

• This study investigated the usefulness of CD4-cell count, CD4-cell percentage (CD4%), HIV-1 load, total lymphocyte count (TLC), BMI and haemoglobin measured at 32 weeks’ gestation as predictors of mortality in a cohort of women in Nairobi, Kenya.
• Mortality rates at 1 and 2 years postpartum were 2.1% (95% CI: 0.7–3.4%) and 5.5% (95% CI: 3.0–8.0%), respectively. CD4-cell count and CD4% had the highest AUC value (>0.9). BMI, TLC and haemoglobin were each associated with but poorly predictive of mortality (positive predictive value <7%). The HIV-1 load did not predict mortality beyond the CD4-cell count.
• Conclusions: The CD4-cell count and CD4% measured during pregnancy were useful predictors of mortality among pregnant women. TLC, BMI, and haemoglobin had limited predictive value. The HIV-1 load did not predict mortality any better than the CD4-cell count alone.

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Comparison of CD4 cell count, viral load, and other markers for the prediction of mortality among HIV-1-infected Kenyan pregnant women.

Brown ER, Otieno P, Mbori-Ngacha DA et al. J Infect Dis 2009;199:1292–1300

• This study investigated the usefulness of CD4-cell count, CD4-cell percentage (CD4%), HIV-1 load, total lymphocyte count (TLC), BMI and haemoglobin measured at 32 weeks’ gestation as predictors of mortality in a cohort of women in Nairobi, Kenya.
• Mortality rates at 1 and 2 years postpartum were 2.1% (95% CI: 0.7–3.4%) and 5.5% (95% CI: 3.0–8.0%), respectively. CD4-cell count and CD4% had the highest AUC value (>0.9). BMI, TLC and haemoglobin were each associated with but poorly predictive of mortality (positive predictive value <7%). The HIV-1 load did not predict mortality beyond the CD4-cell count.
• Conclusions: The CD4-cell count and CD4% measured during pregnancy were useful predictors of mortality among pregnant women. TLC, BMI, and haemoglobin had limited predictive value. The HIV-1 load did not predict mortality any better than the CD4-cell count alone.

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The President's Emergency Plan for AIDS Relief in Africa: An Evaluation of Outcomes.

Bendavid E, Bhattacharya J. Ann Intern Med 2009 Apr 6. [Epub ahead of print]

• This study investigated the effect of the President's Emergency Plan for AIDS Relief (PEPFAR), which started in 2003, on HIV-related deaths, the number of people living with HIV, and HIV prevalence in sub-Saharan Africa.
• From 2004–2007, the difference in the annual change in the number of HIV-related deaths was 10.5% lower in the focus versus control countries (p=0.001). There was no significant difference in the annual growth in the number of people living with HIV.
• Conclusion: After 4 years of PEPFAR activity, HIV-related deaths decreased in sub-Saharan African focus versus control countries but there was no difference in trends of adult prevalence.

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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.

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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

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.

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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.

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A Once-Daily Lopinavir/Ritonavir-Based Regimen Is Noninferior to Twice-Daily Dosing and Results in Similar Safety and Tolerability in Antiretroviral-Naive Subjects Through 48 Weeks.

Gathe J et al. J Acquir Immune Defic Syndr 2009;50:474–81.

• This study compared od and bid dosing of LPV/r plus TDF and FTC od in ARV-naïve patients.
• At week 48, 77% of od vs 76% of bid patients had HIV-1 RNA <50 copies/mL (p=0.715; 95% CI: 5–8%). Response rates, discontinuation rates and adverse events were similar in both groups.
• Conclusions: The response to LPV/r od was noninferior to bid dosing with comparable efficacy and safety. No new PI resistance mutations were detected on virologic rebound.

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National expansion of antiretroviral treatment in Thailand, 2000-2007: program scale-up and patient outcomes

Chasombat S et al. J Acquir Immune Defic Syndr 2009;50:506–12.

• This paper reports the results of the national expansion of an ARV treatment programme in Thailand from 2000 to 2007.
• The initial regimen was NVP plus two NNRTIs in 92.4% of patients. Overall 1-year survival was 0.89 (95% CI: 0.88–0.89). Death was significantly associated with male sex, age >40 years, baseline CD4 count <100 cells/mm3, symptomatic HIV or AIDS, treatment at a district or community hospital and treatment initiation before 2005.
• Conclusions: National ARV treatment programmes can be scaled up rapidly with good patient outcomes. Treatment outcomes were comparable with those for smaller cohorts in other countries and survival rates have improved since 2004.

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Race and sex differences in antiretroviral therapy use and mortality among HIV-infected persons in care.

Lemly DC et al. J Infect Dis 2009 Feb 16. [Epub ahead of print]

• This retrospective cohort study examined all-cause mortality among HIV patients in care on HAART to investigate possible race and sex differences.
• After adjustment for baseline characteristics, death was associated with a number of factors including black race (HR 1.33; p=0.04) and female sex (HR 1.53; p=0.007).
• Conclusions: Race-associated differences in mortality probably resulted from HAART use. Women had an increased mortality risk even after adjustment for HAART use.

Link

Editorial Comment for efficacy and tolerability of initial antiretroviral therapy.

Dorfman D. AIDS 2009;23:355–6.

• Systematic review of initial ART studies investigating efficacy (undetectable plasma HIV viral load by intention-to-treat) and cessation for adverse events.
• Seven variables were independently associated with higher treatment success: non-white race, exclusion for low haemoglobin, lower CD4 cell count, dosing relative to food, dual-nucleoside backbone, NNRTI or ritonavir-boosted PI as the third drug and shorter follow-up. Although the most common cause of treatment cessation, adverse events were reported in only half the studies.
• Conclusion: Multiple reasons influence initial ART success beyond the type of third drug and should be considered when designing and comparing studies. Most studies are too short and report insufficient adverse-event data.

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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.

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Cost-effectiveness analysis of lopinavir/ritonavir and atazanavir+ritonavir regimens in the CASTLE study.

Simpson KN et al. 2009 Feb 14. [Epub ahead of print]

• Cost-effectiveness and budget-impact analysis comparing LPV/r and ATV/r for ARV-naïve patients.
• Use of the LPV/r regimen saved $24,518 and $36,651 at 5 and 10 years, respectively, with lifetime cost savings estimated at $38,490.
• Conclusion: In the CASTLE study, an LPV/r-based regimen in ARV-naïve patients appears to be more cost-effective than an ATV/r-based regimen. The very small added CHD risk predicted by LPV/r treatment is more than offset by the substantial short- and long-term cost savings.

Link

Efficacy and tolerability of initial antiretroviral

Carr A, Amin J. AIDS 2009;23;343–53.

• Systematic review of initial ART studies investigating efficacy (undetectable plasma HIV viral load by intention-to-treat) and cessation for adverse events.
• Seven variables were independently associated with higher treatment success: non-white race, exclusion for low haemoglobin, lower CD4 cell count, dosing relative to food, dual-nucleoside backbone, NNRTI or ritonavir-boosted PI as the third drug and shorter follow-up. Although the most common cause of treatment cessation, adverse events were reported in only half the studies.
• Conclusion: Multiple reasons influence initial ART success beyond the type of third drug and should be considered when designing and comparing studies. Most studies are too short and report insufficient adverse-event data.

Link

Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa.

Lawn SD et al. AIDS 2009;23:335–42.

• Observational community-based study to determine the relationship between mortality risk and the CD4 cell response to ART.
• High mortality in the first year of ART was related to the proportion of time with CD4 cell counts < 200 cells/μL.
• Conclusions: CD4 cell counts are the variable most strongly associated with mortality risk during ART. National HIV programmes in resource-limited settings should be designed to minimize the time patients have CD4 cell counts <200 cells/μL.

Link

Virologic failure endpoint definition in clinical trials: is using HIV-1 RNA threshold <200 copies/ml better than <50 copies/ml? An analysis of ACTG studies.

Ribaudo H et al. CROI 2009;Abstract 580.

• Study evaluating a virological failure (VF) definition of 50 or 200 copies/mL.
• A threshold of 50 copies/mL resulted in a high rate of false-positive VF for many patients who re-suppress to <50 copies/mL without a change in ART.
• Conclusion: A threshold of 200 copies/mL may be preferable to 50 copies/mL.

Link

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

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

Cost-effectiveness analysis of lopinavir/ritonavir and atazanavir+ritonavir regimens in the CASTLE study.

Simpson KN et al. 2009 Feb 14. [Epub ahead of print]

Cost-effectiveness and budget-impact analysis comparing LPV/r and ATV/r for ARV-naïve patients.

Use of the LPV/r regimen saved $24,518 and $36,651 at 5 and 10 years, respectively, with lifetime cost savings estimated at $38,490.

Conclusion: In the CASTLE study, an LPV/r-based regimen in ARV-naïve patients appears to be more cost-effective than an ATV/r-based regimen. The very small added CHD risk predicted by LPV/r treatment is more than offset by the substantial short- and long-term cost savings.

Link

Efficacy and tolerability of initial antiretroviral therapy: a systematic review

Carr A, Amin J. AIDS 2009;23;343–53.

Systematic review of initial ART studies investigating efficacy (undetectable plasma HIV viral load by intention-to-treat) and cessation for adverse events.

Seven variables were independently associated with higher treatment success: non-white race, exclusion for low haemoglobin, lower CD4 cell count, dosing relative to food, dual-nucleoside backbone, NNRTI or ritonavir-boosted PI as the third drug and shorter follow-up. Although the most common cause of treatment cessation, adverse events were reported in only half the studies.

Conclusion: Multiple reasons influence initial ART success beyond the type of third drug and should be considered when designing and comparing studies. Most studies are too short and report insufficient adverse-event data.

Link

Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa.

Lawn SD et al. AIDS 2009;23:335–42. Jan

Observational community-based study to determine the relationship between mortality risk and the CD4 cell response to ART.

High mortality in the first year of ART was related to the proportion of time with CD4 cell counts < 200 cells/μL.

Conclusions: CD4 cell counts are the variable most strongly associated with mortality risk during ART. National HIV programmes in resource-limited settings should be designed to minimize the time patients have CD4 cell counts <200 cells/μL.

Link

Virologic failure endpoint definition in clinical trials: is using HIV-1 RNA threshold <200 copies/ml better than <50 copies/ml? An analysis of ACTG studies.

Ribaudo H et al. CROI 2009;Abstract 580. Feb

Study evaluating a virological failure (VF) definition of 50 or 200 copies/mL.

A threshold of 50 copies/mL resulted in a high rate of false-positive VF for many patients who re-suppress to <50 copies/mL without a change in ART.

Conclusion: A threshold of 200 copies/mL may be preferable to 50 copies/mL.

Link

Article Index