New Publications in HIV : Archive

06 May 2009

Challenges for Scaling up ART in a Resource-Limited Setting: A Retrospective Study in Kibera, Kenya.

Unge C et al. J Acquir Immune Defic Syndr 2009 Feb 12. [Epub ahead of print] • This retrospective cohort study investigated levels of dropout and adherence in an ART programme in Kibera, Kenya.
• The dropout rate was 23 per 100 person-years and the probability of retention in the program at 6, 12 and 24 months was 0.83, 0.74 and 0.65, respectively.
• Conclusion: Despite free drugs and low associated costs, dropout probabilities were higher and adherence lower versus other sub-Saharan Africa studies. The results show that ART programs in resource-limited settings risk low adherence and retention rates when expanding services.
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 15 May 2009

Low levels of antiretroviral-resistant HIV infection in a routine clinic in Cameroon that uses the World Health Organization (WHO) public health approach to monitor antiretroviral treatment and adequacy with the WHO recommendation for second-line treatmen

Kouanfack C, Montavon C, Laurent C et al. Clin Infect Dis 2009;48:1318–22. • This cross-sectional study was conducted at a routine HIV/AIDS clinic in Cameroon using the WHO public health approach to treatment.
• The results showed low rates of virological failure and drug resistance at 12 and 24 months after initiation of ART.
• The results also showed that the WHO recommendation for second-line treatment would be effective in almost all patients with HIV drug-resistance mutations.
Link 15 May 2009

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.
Link 08 June 2009

HIV-related lipodystrophy in Africa and Asia.

Womack J. AIDS Read 2009;19:131–9, 148–52. • This article reviews the literature on lipodystrophy in Africa and Asia.
• Lipodystrophy in resource-constrained settings has significant implications for patient health, QoL and long-term adherence.
• Lipoatrophy may be an important adverse effect of ART in Africa and Asia.
• Although a causative link has not been identified from the literature, the consistent evidence from the West means that it is reasonable to support the WHO’s effort to remove d4T from first-line therapy options.
• Affordability and access to alternative NRTIs and the newer ARV classes are key issues.
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 09 June 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, 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.
Link 24 August 2009

High frequency of clinically significant mutations after first-line generic highly active antiretroviral therapy failure: implications for second-line options in resource-limited settings.

Kumarasamy N, Madhavan V, Venkatesh KK et al. Clin Infect Dis 2009;49:306–9. • Continuing failed ART regimens may lead to the accumulation of mutations, potentially limiting options for second-line treatment.
• This study investigated the pattern of drug-resistance mutations among 138 Indian patients who experienced failure of first-line NNRTI-based ART.
• Conclusions: There was a high frequency of drug-resistance mutations in patients who experienced immunological treatment failure. This suggests a need for VL monitoring.
Link 24 August 2009

Virological monitoring and resistance to first-line highly active antiretroviral therapy in adults infected with HIV-1 treated under WHO guidelines: a systematic review and meta-analysis.

Gupta RK, Hill A, Sawyer AW, Cozzi-Lepri A et al. Lancet Infect Dis. 2009;9:409–17. • This meta-analysis assessed the effect of variable monitoring on the emergence of resistance after therapy with commonly used drug combinations by reviewing studies reporting resistance in patients infected with HIV and a CD4 count of <200 cells/μL treated with two NRTIs and an NNRTI.
• Resistance at VF to NNRTIs at 48 weeks was 88.3% (95% CI: 82.2–92.9) in infrequently monitored patients, compared with 61.0% (95% CI: 48.9–72.2) in frequently monitored patients (p<0.001).
• Lamivudine resistance was 80.5% (95% CI: 72.9–86.8) and 40.3% (95% CI: 29.1–52.2) in infrequently and frequently monitored patients, respectively (p<0.001).
• The prevalence of at least one thymidine analogue mutation was 27.8% (95% CI: 21.2–35.2) and 12.1% (95% CI: 5.9–21.4), respectively (p<0.001).
• Genotypic resistance at 48 weeks to lamivudine, NRTIs and NNRTIs was substantially higher in patients who were less frequently monitored.
• Conclusion: There is a need for cheap point-of-care VL tests to identify early viral failures and limit the emergence of resistance.
Link 16 September 2009

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.
Link 16 September 2009

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.
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 16 November 2009

Operational research in low-income countries: what, why, and how?

Zachariah R, Harries AD, Ishikawa N et al. Lancet Infect Dis 2009;9:711–7. • This article provides a definition of operational research, clarifies its relevance to infectious-disease control programmes and describes some of the factors and challenges for its integration into programmes.
• Investment in operational research is needed to enable more efficient healthcare, particularly in areas with a high disease burden and limited resources.
• Research capacity needs to be developed, specific resources allocated, and different stakeholders (e.g. academic institutions, national programme managers, and non-governmental organisations) brought together to promote operational research.
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 11 January 2010

Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.

DART Trial Team. Lancet [Epub ahead of print • This study investigated the possible long-term effects on clinical outcomes of routine toxicity and efficacy monitoring of HIV+ patients receiving ART in Uganda and Zimbabwe.
• HIV+ adults with CD4 counts >200 cells/μL starting ART were randomly assigned to laboratory and clinical monitoring or clinically driven monitoring.
• The primary endpoints were new WHO stage 4 HIV events or death and serious adverse events.
• In the clinically driven monitoring group, 459 (28%) patients versus 356 (21%) in the laboratory and clinical monitoring had a new WHO stage 4 event or died (p=0.0001) and 283 (17%) versus 260 (16%) patients had a new serious adverse event (HR 1.12 [95% CI: 0.94–1.32]; p=0.19).
• Conclusions: ART can be delivered safely without routine laboratory monitoring. Differences in disease progression suggest a role for CD4-cell count monitoring to guide the switch to second-line treatment from the second year of ART.
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 22 March 2010

Impact of antiretroviral therapy on incidence of pregnancy among HIV-infected women in Sub-Saharan Africa: a cohort study.

Myer L et al. PLoS Med 2010;7:e1000229. • This study investigated whether ART influences pregnancy rates by analyzing data from 11 Mother-to-Child Transmission-Plus (MTCT-Plus) Initiative programs in seven African countries.
• In total, 589 pregnancies were observed among 4,531 women (incidence: 7.8/100 person-years).
• The rate of new pregnancies was significantly higher among women receiving ART (9.0/100 person-years) than those not on ART (6.5/100 person-years) (adjusted HR: 1.74; 95% CI: 1.19–2.54).
• Conclusions: ART was associated with a significantly higher pregnancy rate among HIV+ women in sub-Saharan Africa. The results indicate the importance of pregnancy planning and management as a component of HIV care services
Link 22 March 2010

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.
Link 07 June 2010

Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis

Donnell D et al. Lancet 2010 May 27. • This study investigated the effect of ART use by HIV+ heterosexual African adults on the risk of transmission to their uninfected partners.
• Only one of 103 genetically-linked HIV-1 transmissions was from an infected patient who had started ART, corresponding to a transmission rate of 0•37 (95% CI: 0•09–2•04) per 100 person-years in those who had initiated treatment and 2•24 (95% CI: 1•84–2•72) per 100 person-years in those who had not, a 92% reduction (adjusted incidence rate ratio: 0•08; 95% CI: 0•00–0•57; p=0•004).
• In people not on ART, the highest HIV-1 transmission rate (8•79 per 100 person-years) was in those with a CD4 cell count <200 cells/mm3. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count >200 cells/mm3, 70% (66/94) of transmissions occurred when plasma HIV RNA was >50,000 copies/mL.
• Conclusions: Low CD4 cell counts and high plasma HIV RNA levels may be beneficial in guiding the use of ART to help prevent transmission and achieve population-level reductions in HIV-1 transmission.
Link 07 June 2010

HIV drugs for treatment, and for prevention.

Dabis F et al. Lancet 2010 May 27. • This study investigated the effect of ART use by HIV+ heterosexual African adults on the risk of transmission to their uninfected partners.
• Only one of 103 genetically-linked HIV-1 transmissions was from an infected patient who had started ART, corresponding to a transmission rate of 0•37 (95% CI: 0•09–2•04) per 100 person-years in those who had initiated treatment and 2•24 (95% CI: 1•84–2•72) per 100 person-years in those who had not, a 92% reduction (adjusted incidence rate ratio: 0•08; 95% CI: 0•00–0•57; p=0•004).
• In people not on ART, the highest HIV-1 transmission rate (8•79 per 100 person-years) was in those with a CD4 cell count <200 cells/mm3. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count >200 cells/mm3, 70% (66/94) of transmissions occurred when plasma HIV RNA was >50,000 copies/mL.
• Conclusions: Low CD4 cell counts and high plasma HIV RNA levels may be beneficial in guiding the use of ART to help prevent transmission and achieve population-level reductions in HIV-1 transmission.
Link 07 June 2010

Decline in early life mortality in a high HIV prevalence rural area of South Africa: evidence of HIV prevention or treatment impact?

Ndirangu J et al. AIDS 2010;24:593–602. • This retrospective study investigated the temporal and spatial associations between early life mortality rates and a prevention of mother-to-child transmission (PMTCT) programme (single-dose NVP), an HIV treatment programme and maternal HIV in a largely rural population with a high prevalence of antenatal HIV.
• Mortality was independently associated with birth season (adjusted HR: 1.16; 95% CI: 1.02–1.33), maternal education (HR: 1.21; 95% CI: 1.02–1.43), maternal HIV (HR: 4.34; 95% CI: 3.11–6.04) and ART availability (HR: 0.46; 95% CI: 0.33–0.65).
• Children born at home (unlikely to have received PMTCT) had a 35% higher risk of dying than children born in a facility where PMTCT was available (HR: 1.35; 95% CI: 1.04–1.74).
• Conclusions: The results confirm the importance of maternal survival and show the importance of the PMTCT and maternal HIV treatment in improving the survival of their young children.
Link 25 June 2010

Body mass index and risk of tuberculosis and death.

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

Nurse versus doctor management of HIV-infected patients receiving antiretroviral therapy (CIPRA-SA): a randomised non-inferiority trial.

Sanne I et al. Lancet 2010 Jun 15 • This study compared outcomes of nurse versus doctor management of ART care for HIV+ patients in two South African primary-care clinics.
• 371 (46%) patients reached an endpoint of treatment failure: 192/404 (48%) in the nurse group and 179/408 (44%) in the doctor group. The HR for composite failure was 1.09 (95% CI: 0.89–1.33), which was within the limits for non-inferiority.
• After a median follow-up of 120 weeks (IQR 60–144), deaths (10 vs 11), virological failures (44 vs 39), toxicity failures (68 vs 66) and programme losses (70 vs 63) were similar in the nurse and doctor groups, respectively.
• Conclusion: Nurse-monitored ART is non-inferior to doctor-monitored therapy. The results support the use of appropriately trained nurses for monitoring ART.
Link 25 June 2010

Operational research in HIV priority areas: the African way.

Boyd MA, Nwizu CA. Lancet. 2010 Jun 15. • This study compared outcomes of nurse versus doctor management of ART care for HIV+ patients in two South African primary-care clinics.
• 371 (46%) patients reached an endpoint of treatment failure: 192/404 (48%) in the nurse group and 179/408 (44%) in the doctor group. The HR for composite failure was 1.09 (95% CI: 0.89–1.33), which was within the limits for non-inferiority.
• After a median follow-up of 120 weeks (IQR 60–144), deaths (10 vs 11), virological failures (44 vs 39), toxicity failures (68 vs 66) and programme losses (70 vs 63) were similar in the nurse and doctor groups, respectively.
• Conclusion: Nurse-monitored ART is non-inferior to doctor-monitored therapy. The results support the use of appropriately trained nurses for monitoring ART.
Link 25 June 2010

Antiretroviral regimens in pregnancy and breast-feeding in Botswana.

Shapiro RL et al. N Engl J Med 2010;362:2282–94. • This randomised study investigated the efficacy HAART regimens to prevent mother-to-child transmission of HIV-1.
• Women received ABC/3TC/AZT (NRTI group), LPV/r + AZT/3TC (PI group) or NVP/3TC/AZT (observational group). Infants received single-dose NVP and 4 weeks of AZT.
• The rate of virological suppression to <400 copies/mL was high and did not differ significantly between the three groups at delivery (NRTI 96%, PI 93% and observational 94%) or during breast feeding (NRTI 92%, PI 93% and observational 95%).
• By 6 months of age, 8/709 live-born infants (1.1%) were infected (95% CI: 0.5–2.2): six were infected in utero (four in the NRTI, one in the PI and one in the observational group) and two were infected during breast feeding (in the NRTI group).
• Treatment-limiting adverse events occurred in 2% of women in the NRTI and PI groups and 11% of women in the observational group.
• Conclusions: All regimens resulted in high rates of virological suppression, with an overall mother-to-child transmission rate of 1.1%.
Link 25 June 2010

Maternal or infant antiretroviral drugs to reduce HIV-1 transmission.

Chasela CS et al. N Engl J Med 2010;362:2271–81. • This study investigated the efficacy of a maternal triple-drug ARV regimen or infant NVP prophylaxis for 28 weeks during breast-feeding to reduce post-natal transmission of HIV-1 in Malawi.
• All mothers and infants received perinatal prophylaxis with single-dose NVP and 1 week of AZT plus 3TC.
• Among mother-infant pairs, 5.0% of infants were HIV+ at 2 weeks.
• The estimated risk of HIV-1 transmission at 2–28 weeks was higher in the control group (5.7%) than in either the maternal- (2.9%, p=0.009) or the infant-regimen group (1.7%, p<0.001).
• The estimated risk of infant HIV-1 infection or death at 2–28 weeks was 7.0% in the control group, 4.1% in the maternal- (p=0.02), and 2.6% in the infant-regimen group (p<0.001).
• Conclusions: The use of either a maternal ARV regimen or infant NVP for 28 weeks was effective in reducing HIV-1 transmission during breast feeding.
Link 05 July 2010

Nevirapine-associated early hepatotoxicity: incidence, risk factors, and associated mortality in a primary care ART programme in South Africa.

Chu KM et al. PLoS One 2010;5:e9183. • This study investigated NVP-associated hepatotoxicity among 1,809 HIV+ ARV-naïve adults starting NVP-based therapy.
• The cumulative proportion of early hepatotoxicity was 1–2%, giving an incidence rate at 102 days of 3.6–7.6 per 100 person-years. The median time to hepatotoxicity was 32 days (IQR 28–58 days).
• No association was found between age, gender, baseline CD4 count, concurrent TB infection, prior participation in a programme to prevent mother-to-child-transmission, or baseline weight and early hepatotoxicity.
• Hepatotoxicity was not associated with mortality.
• Conclusions: The cumulative proportion of early hepatotoxicity with NVP-based ART was low in this resource-constrained setting.
Link 05 July 2010

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

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

Effectiveness of non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in women previously exposed to a single intrapartum dose of nevirapine: a multi-country, prospective cohort study.

Stringer JSA et al. PLoS Med 2010 Feb 16;7(2):e1000233. • This study investigated whether women with prior exposure to single-dose NVP would have a higher prevalence of failure with an NNRTI-containing regimen during the first 48 weeks of treatment than women without prior exposure.
• Women who died, discontinued NNRTI-containing ART or had a confirmed plasma VL ≥400 copies/mL were designated treatment failures.
• Overall, 114/355 NVP-exposed (32.1%) and 132/523 NVP-unexposed women (25.2%) were treatment failures (6.9% difference in failure rate; 95% CI: 0.8–13.0%).
• Locally weighted regression analysis indicated a clear inverse relationship between VF and exposure interval.
• Conclusions: Prior exposure to single-dose NVP was associated with an increased risk of treatment failure but this was largely confined to women with more recent exposure. Women needing ART within 12 months of NVP treatment should not be prescribed an NNRTI-containing regimen as first-line therapy.
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