Tag Archives: Journal of Acquired Immune Deficiency Syndromes

HIV treatment breaks lead to drug resistance in the female genital tract

Antiretroviral treatment interruptions of 48 hours or more are associated with the emergence of resistant strains of HIV in the female genital tract, investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

The study included 102 women in Kenya who started first-line antiretroviral therapy based on a non-nucleoside reverse transcriptase inhibitor (NNRTI). Drug-resistant virus was detected in the genital tract of five women in the twelve months after treatment was started. Treatment interruptions were the most important risk factor for this outcome.

“We found that ART [antiretroviral therapy] adherence was a key determinant of genital tract resistance and that treatment interruptions of whatever cause lead to a substantial increase in the hazard of detecting genotypic resistance to antiretrovirals in female genital tract secretions,” write the authors. “Efforts to prevent treatment interruptions by improving program effectiveness, promoting adherence and timely refills, and avoiding the use of more toxic antiretroviral agents could therefore play an important role in reducing transmitted drug resistance.”

First-line HIV therapy often comprises two nucleoside reverse transcriptase inhibitors (NRTIs) combined with an NNRTI. This treatment can have a powerful and durable anti-HIV effect. However, it requires high levels of adherence. Drug-resistant strains of HIV can emerge with poorer adherence. Older drugs in the NNRTI class, nevirapine (Viramune) and efavirenz (Sustiva or Stocrin), have a low barrier to resistance.

Little is currently known about the emergence of drug-resistant virus in the genital tract of women treated with NNRTI-based therapy. This is an important gap in knowledge as drug-resistant virus is potentially transmissible.

Investigators therefore designed a prospective study involving women who started first-line HIV treatment in Mombasa between 2005 and 2008. During the first twelve months after starting therapy viral load was monitored at three-monthly intervals in both plasma and the genital tract. Samples with viral load above 1000 copies/ml were sent for resistance testing. The investigators conducted analysis to see which factors were associated with the emergence of drug-resistant virus in the genital tract.

Overall, the women had high levels of adherence to their antiretroviral therapy. Assessed by pill count, median adherence was 97%. However, there were 40 treatment interruptions. Their median duration was four days. Median pill-count adherence following treatment interruptions was just 83%.

Drug-resistant virus was detected in the blood of nine women (incidence, 10 per 100 person-years) and in the genital secretions of five individuals (incidence, 5.5 per 100 person-years). All five women with resistant HIV in their genital secretions also had resistant virus in their blood.

The investigators’ first set of analysis showed that a number of factors were associated with genital tract resistance. These included treatment interruptions (p = 0.006), pill-count adherence (p = 0.001) and a higher baseline viral load (p = 0.04).

But only treatment interruptions remained significant after controlling for potentially confounding factors. Interruptions were associated with a more than 14-fold increase in the risk of genital tract resistance (aHR = 14.2; 95% CI, 1.3-158.4; p = 0.03).

“The reasons for treatment interruption in this study included both unavoidable discontinuations due to drug toxicity or systemic illness and avoidable interruptions due to late refills, when it is likely that consecutive doses were missed,” note the investigators. “Despite a comprehensive program of adherence support including pre-ART counseling, directly administered therapy during the first month of treatment, a support group, pill boxes and transportation reimbursements, we were unable to prevent these events.”

Transport problems and pharmacy stock-outs have emerged as major barriers to adherence in resource-limited settings. The investigators are concerned that “such barriers may lead to the development of genital tract resistance due to treatment interruptions, suggesting an increased risk for transmission of drug-resistant virus”.

The Aids Library of Philadelphia FIGHT has a video on YouTube which explore the subject of HIV which is resistant to anti-HIV medications. Further information can be found on their website.

Original Article via NAM and Philadelphia Fight’s YouTube Channel

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HIV treatment integrated into general health care delivers ‘equal or better’ results in MSF programmes

Outcomes for people taking antiretroviral treatment in Médecins sans Frontières’ (MSF) integrated general healthcare programmes were as good or better than those in vertical HIV programmes, researchers report in a nine-country study published the advance online edition of the Journal of Acquired Immune Deficiency Syndromes.

While those in integrated programmes may have started ART at a more advanced disease stage, the risk of death was similar to those in vertical programmes but loss to follow-up was less (aHR 1.02; 95% CI: 0.83-1.24 and aHR 0.71; 95% CI: 0.61-0.83, respectively) among patients followed for up to 30 months.

The authors say this analysis of retrospective observational cohort data from 17 programmes (seven vertical and 10 integrated) on ART delivery and care “validates the programme design of integration and its associated benefits.”

The success of scale-up of access to ART in resource-poor settings with outcomes matching those of resource-rich settings has been achieved primarily through large-scale vertical treatment programmes, notably in urban areas.

However, resource demands make vertical programmes neither feasible nor appropriate in rural settings or in areas of low HIV prevalence with other competing health issues.

The authors suggest programmes integrating HIV care into other health activities offer a possible feasible alternative model using HIV resources and staff to provide both HIV and non-HIV services.

Benefits include:

  • Improved access to HIV care in areas where vertical programmes are not feasible.
  • Retention in care made easier since services are both closer to the patient and spread across disciplines.
  • Strengthened health programmes as HIV often brings additional resources including clinical training, improved laboratory services and procurement supply systems.
  • HIV treated as any other illness may reduce stigma.
  • Same staff able to treat many different conditions in the same place.
  • Improved programme cohesiveness.

Yet, the advantages that integration brings may mean sacrificing the quality of care that dedicated services and specialised staff provide in vertical programmes. With this in mind the authors chose to compare outcomes of patients treated with ART in MSF’s integrated and vertical HIV programmes.

Vertical programmes were defined as specifically designed to treat HIV in a population. Integrated programmes were defined as providing comprehensive health care within which HIV was included as part of general healthcare services.

Although programmes differed in their degree of integration into general health services, all testing and treatment protocols, adherence counselling and patient follow-up, data collection and monitoring, laboratory protocols and drug supply and procurement were standardised across all MSF programmes; and out-of-programme training and advisory staff were the same. Drugs and materials were supplied through MSF but the programmes were integrated into Ministry of Health facilities.

The authors used Cox regression to determine the link between death and programme design, adjusting for potential confounders including gender, and at baseline: age, body mass index, clinical WHO stage, tuberculosis; programme age at the patient’s start of ART (providing ART for 12 months or more or less than 12 months) and setting (rural or urban).

Ninety per cent (15876) of the 17,561 adults who started ART in the 17 programmes were treated in the vertical programmes with the remaining 10% (1685) in the integrated programmes. Eighty-eight per cent (15,403) had at least six months of follow-up for inclusion in the 12-month treatment outcome analysis. 14,523 had complete data for inclusion in the Cox regression.

Median time on ART for all patients was 12.7 months (IQR: 4.5-24.0) and 6.8 months (IQR: 2.3-15.0) for vertical and integrated programmes, respectively.

Before adjusting for possible confounders, estimates showed a higher proportion of deaths in integrated programmes, 11.9% compared to 7.9%. The authors suggest this is explained because patients were more clinically immunosuppressed at baseline (a higher proportion at WHO clinical stage 4).

This is in keeping with other findings. Patients targeted in integrated programme often present for care when they are already sick. In contrast, the authors note, to vertical programmes that do large-scale community counselling and testing so attracting more asymptomatic patients.

After adjusting for other factors the Cox proportional hazards model showed the risks of death were similar in both programmes, with clinical WHO stage at the start of ART the most significant influence (aHR 1.99, 95% CI: 1.74-2.29). And, the risk of loss-to-follow-up was 29% less in integrated than in vertical programmes.

Reasons include, the authors suggest, integrated services allow for better treatment of co-existing illnesses, including tuberculosis; lower patient numbers mean more individualised care and follow-up; easier access with services closer to the patient; and normalisation of HIV reduces stigma.

The authors note these findings are comparable to other published studies. They cite the ART-LINC cohort of 18 programmes in low-income settings in Africa, Asia and Latin Americas. Combined death and loss to follow-up rates were 21%, 19% and 24% for ART-LINC, MSF vertical and integrated programmes, respectively.

The greater the programme experience, the more protective it was against death (aHR 0.77, 95% CI: 0.66-0.89).

However, risk of loss to follow-up was greater in more experienced programmes (aHR 3.33, 95% CI: 2.92-3.79). The authors suggest as programmes grow in size less time is spent on patient selection, preparation and counselling for ART adherence.

Not surprisingly, the risk was even greater among patients treated in rural settings (aHR 3.82, 95% CI: 3.49-4.20) because of travel distances and limited travel options, note the authors.

Limitations include: the Cox hazards model, because of the body mass index variable, did not follow the assumption of proportional hazards, so potentially reducing its power.

Vertical programmes were larger and predominantly in urban centres so may have had an unmeasured effect on outcomes.

The range of programmes from different countries over a number of years supports the generalizability of the findings yet data quality, in spite of a standardised database, may have varied.

Sensitivity analyses, however, did not change the main findings.

The authors conclude “In a time of intense debate regarding the merits of specific funding to HIV services, our data provide evidence in these settings [rural and relatively low prevalence) that resources dedicated to HIV through integrated programmes can benefit the individual patient, and as previously described can also strengthen the health system as a whole.”

Original Article by Carole Leach-Lemens at NAM

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Big Increase In Repeat Pregnancy Rates In HIV-Positive Women In UK & Ireland

Rates of repeat pregnancies among HIV-positive women in the UK and Ireland have increased substantially since 1997, investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

In 2009 over a third of all pregnancies involved women who had at least one other pregnancy. Younger age and geographic region of origin were associated with having a subsequent pregnancy.

“A substantial and increasing proportion of pregnancies in diagnosed HIV-infected women are occurring in those who have already received HIV-related care in one or more previous pregnancy,” comment the authors. “The main demographic characteristics independently associated with repeat pregnancies were younger age…and being born in Middle or Western Africa.”

A large proportion of HIV-positive women are of childbearing age. However, mother-to-child transmission can be prevented in most cases with appropriate antiretroviral treatment and care. This low risk of transmission combined with the excellent prognosis provided by modern antiretroviral treatment means that HIV-positive women in resource-rich countries can realistically consider childbearing.

In the UK and Ireland the number of pregnancies in HIV-positive women has increased significantly over the last decade. A significant proportion of these women have experienced at least one other pregnancy while receiving HIV care. Given their often complex medical, obstetric and social needs, the care of this group of women can be complex.

Despite this, little is currently known about the demographics and health status of HIV-positive women who experience repeat pregnancies.

Therefore investigators from the National Study of HIV in Pregnancy and Childhood examined 20 years of data obtained from pregnant HIV-positive women in the UK and Ireland. Data from 1990 and 2009 were included in the study.

The investigators’ aims were to characterise the pattern and rate of repeat pregnancies and to establish the demographic and clinical characteristics of HIV-positive women with two or more recorded pregnancies.

A total of 14096 pregnancies were recorded in HIV-positive women during the study period. Just over a quarter (2737; 26%) were repeat pregnancies. This figure included 2117 women who had two pregnancies, 475 with three pregnancies and 145 with four or more pregnancies.

Outcomes were recorded for 13,355 pregnancies. In all, 11,915 (89%) resulted in a live birth, 121 (1%) in a still birth and 10% in either miscarriage or termination.

Both the number and proportion of repeat pregnancies increased significantly. There were 158 recorded pregnancies in 1997, and 32 (20%) were repeat pregnancies. By 2009, the total number of pregnancies had increased to 1465, with 565 (37%) being repeat pregnancies.

Further analysis of the 2009 figures showed that 28% were second pregnancies, 7% were third and 3% were fourth or subsequent pregnancies.

“The increase in repeat pregnancies over the last two decades is likely to reflect a combination of factors including the accumulation of diagnosed HIV-infected women who have already had pregnancy,” suggest the investigators. “Major improvements in quality of life and AIDS-free survival of people living with HIV, and substantial reductions in the risk of mother-to-child-transmission are also likely to have had an impact.”

Overall, the rate of repeat pregnancies was 6.7 per 100 woman-years.

The median interval between first and second deliveries was 2.7 years, with an interval of 2.3 years between second and third deliveries, with the same interval between third and fourth deliveries.

Analysis of the factors associated with repeat pregnancy was restricted to women who received care after 2000. A total of 11,426 pregnancies in 8661 women were therefore included. Just over a quarter (26%) were repeat pregnancies.

The probability of a repeat pregnancy declined significantly with increasing age (p < 0.001).

Women born in central African countries and West Africa were more likely to experience sequential pregnancies than women born in other regions.

“This pattern is likely to reflect a complex range of cultural, behavioural and migratory factors such as fertility patterns in women’s countries of origin and the demographics of women who migrate from different regions,” write the researchers.

There was no robust evidence that either CD4 cell count or health were associated with repeat pregnancies.

“The number of diagnosed HIV-infected women in the UK and Ireland having more than one pregnancy has increased substantially and is likely to continue to grow,” conclude the authors.

They stress the importance of understanding the characteristics of these repeat pregnancies. “Variations in the probability of repeat pregnancies, according to demographic characteristics, are important considerations when planning the reproductive health services and HIV care for people living with HIV.”

Original Article via Michael Carter at NAM

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September Round Up

If you’re reading this, the chances are you’re subscribed or receiving this news via Twitter but just in case you’re a casual browser why not stay a while, subscribe or follow us and read up on LASS and HIV/STI updates.  Here’s a brief roundup from last month’s posts

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GOVERNMENT & UK

A House of Lords Select Committee published a damning report on HIV in the UK, warning that the current priority given to HIV and Aids treatment by policy makers is ‘woefully inadequate’, and revealing that over 100,000 people in the UK will be living with the disease by next year. The Lords Select Committee on HIV and Aids in the UK also warned that the total cost of treatment would soon top £1 billion per year, and called for all new patients at GPs’ surgeries to be tested for the illness on an opt-out basis.

The Government announced last month that the rules on gay men donating blood will change from a lifetime ban to a 12 month deferral period.  This decision follows a review of the current policies around exclusion and deferral from blood donation by the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO).

Employing sport to communicate HIV messages isn’t new, but one initiative aims to go further – imparting skills for planning, evaluating and funding a football-based HIV campaign
Follow LASSleics on TwitterSCIENCE

Scientists in the US have developed a strain of green-glowing cats with cells that resist infection from a virus that causes feline AIDS, a finding that may help prevent the disease in cats and advance AIDS research in people.

Raising the CD4 cell threshold for the initiation of antiretroviral therapy to 500 cells/mm3 would mean that almost 50% of patients would need to start HIV treatment within a year of their infection with HIV, investigators from an international study of seroconverters report in the October 15th edition of Clinical Infectious Diseases.

Scientists spent a decade trying—and failing—to map the structure of an enzyme that could help solve a crucial part of the AIDS puzzle. It took online gamers all of three weeks.

Spanish researchers have completed the first human trial of a new vaccine against HIV. It has been successful in 90% of the HIV-free volunteers during phase I testing. This vaccine brings great hope to eradicate HIV forever.
Follow LASSleics on TwitterINTERNATIONAL

The Zimbabwe government says it is considering drastic measures of door-to-door HIV testing campaigns for every citizen in the country in a move to try and eliminate new HIV infections.

Linkage to facility-based HIV care from a mobile testing unit is feasible, South African researchers report in the advance online edition of the Journal of Acquired Immune Deficiency Syndromes.  In a stratified random sample of 192 newly diagnosed individuals who had received CD4 test results, linkage to care was best among those who were ART eligible, Darshini Govindasamy and colleagues found.

The David Kato Vision & Voice Award will be presented annually, on Human Rights Day (10th December), to an individual who demonstrates courage and outstanding leadership in advocating for the sexual rights of lesbian, gay, bisexual, transgender and intersex (LGBTI) people, particuarly in enviroments where these uinduvidual face continued rejection, marginalization, isolation and persecution.  David Kato, the advocacy officer for Sexual Minorities Uganda was one of Uganda’s most prominent gay rights activists until January, when he was murdered in his home weeks after winning a court victory over a tabloid that called for homosexuals to be killed.  Read more about it here.
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Each month, a registered dietician from the NHS, visits LASS to offer helpful advice and information on food nutrition and healthy eating for people who live with HIV.  Our next session “The Truth About Fats” will be on Friday, 16th September 2011 from 12:00pm.  This is an opportunity to ask questions and speak with the dietitian directly about any concerns you may have.

Well done to TRADE Sexual Health after a very successful Gay Pride.  This year’s Leicester Gay Pride saw Trade Sexual Health join forces yet again with the Leicester GUM Clinic to present the Health & Wellbeing Marquee 2011!

  • Excellent strategy, well communicated.
  • Excellent and trusted leadership.
  • Excellent coaching and mentoring across the organisation.

These are just three of the positive statements used to describe Leicestershire AIDS Support Services by Investors in People after our recent assessment.  We are proud to announce that we are now officially recognised as an investor in people organisation.

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Mobile Testing Units Show Success in Linking People to HIV Care

Linkage to facility-based HIV care from a mobile testing unit is feasible, South African researchers report in the advance online edition of the Journal of Acquired Immune Deficiency Syndromes.

In a stratified random sample of 192 newly diagnosed individuals who had received CD4 test results, linkage to care was best among those who were ART eligible, Darshini Govindasamy and colleagues found.

The lower the CD4 cell count the greater the linkage to care: all of those with CD4 counts at or under 200 cells/mm3, two-thirds of those with CD4 counts of 201-350 cells/mm3 and a third of those with CD4 counts over 350 cells/mm3 linked to care.

An estimated two million people died as a result of HIV/AIDS in sub-Saharan Africa in 2008. South Africa now has the largest ART programme in the world, yet half of those in need of treatment do not get it. And a large number of those who do present for care, present late with low CD4 cell counts increasing their risk of early death.

In South Africa traditional HIV counselling and testing (HCT) sites at stationary facilities have increased and consequently so have the numbers tested. Yet this has not resulted in increased numbers on treatment and in care.

Transport costs, being male and having a low CD4 cell count have been well documented as the primary barriers of non-linkage to care.

Successful early diagnosis of HIV has to be accompanied by strategies that assure timely linkage to care and treatment so improving health outcomes.

Mobile testing units offer several advantages: people are often tested at an earlier stage of HIV; it is easier for hard-to-reach and high-risk populations to test; and they are cost-effective. However, maintaining on-going HIV care may prove difficult, requiring referral to stationery facilities.

The authors note no studies have looked at the performance of mobile testing units in linking people diagnosed with HIV to care at public health facilities.

The authors chose to look at whether disease progression as defined by CD4 cell count had an effect on access to care and the associated barriers in a nurse-run, counsellor-supported mobile testing unit.

From August 2008 until December 2009 those diagnosed for the first time with HIV were identified retrospectively from the mobile unit records. Those who got a CD4 cell count were prospectively followed from April to June 2010 to determine linkage to HIV care.

The unit, in the Cape Metropolitan region, Western Cape, South Africa, provides free HCT services to underserved communities.

Along with free client-initiated HCT free screening for other chronic conditions including high blood pressure, diabetes and obesity as well as TB is offered. The population is predominantly black Xhosa-speaking Africans.

Following rapid testing and a positive result and CD4 testing individuals are given detailed referral letters to help their access to care. Individuals are called when results of CD4 counts are available (within 72 hours). Those with no contact number are followed up by home visit or letter. Counselling is provided and patients are encouraged to go to clinics for either pre-ART care or to start ART as appropriate.

Of the 6738 records, overall prevalence of new diagnosis was 6.9% (463), of which 376 met the study’s inclusion criteria.

Because of a higher proportion of patients with CD4 counts at or above 350 cells/mm3 the authors took one-third of patients from this cohort (76), together with all 36 individuals with CD4 cell counts at or below 200 cells/mm3, and the 80 patients with CD4 counts between 201 and 350 cells/mm3.

Of the sample 27% (43) did not get their CD4 test result. Being female, having a CD4 cell count at or under 350 cells/mm3 and having a cellphone improved the likelihood of getting a CD4 count result. These results echo recent studies in South Africa showing a high loss to follow-up prior to receiving a CD4 test result; highlighting the critical need for point of care CD4 testing in both mobile and stationary facilities.

Of the 145 (73%) remaining individuals 10 refused to participate and 56 could not be traced in spite of previously having been contacted and receiving their CD4 counts.

52.5% (49) linked to care, including 100% of those ART-eligible. While the sample size is small, note the authors, the results are considerably higher than in studies of stationary facilities, where rates of post-diagnosis linkage to care varied from 30% to 80% among the ART-eligible.

Over 70% said that the mobile unit’s referral letter helped them access care at a public health facility.

Nonetheless over 30% of those eligible to start ART still had not started two months after their diagnosis but were still in the ART screening process. These results support other studies in sub-Saharan Africa also showing a delay in starting ART after diagnosis.

Having a higher CD4 count, no TB symptoms, not having disclosed and being employed increased the risks of not accessing care.

Not being able to access public health facilities was the most common barrier reported (41%) to linking to care. Other barriers included: 13% worried about ART toxicity and side effects and 9% fearing stigma and disclosure.

Extending hours and opening on the weekends at public facilities and setting up workplace programmes with mobile units could improve linkage to care for the employed, note the authors.

Limitations include the small sample size; the inability to track over 40% of eligible study participants in spite of persistent follow-up so potentially biasing the findings; and incorrect contact information. The study was undertaken 6-18 months after HIV diagnosis makingfollow-up especially challenging.

Strengths include validation of self-reported linkage to HIV care; trained bilingual counsellors assured minimal respondent bias; no incentives were given for participation.

The authors note HIV services at the mobile unit and public health facilities were free so their findings can be generalised to similar settings.

The authors conclude that while linkage to care was best among those ART-eligible, there is an urgent need to design interventions to improve linkage to care for the employed.

Original Article by Carole Leach-Lemens at Nam

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LASS offer a completely free and confidential rapid HIV test and you’ll get the results within 60 seconds from a simple finger prick test.  We use the Insti HIV test produced by BioLytical laboratories.  The test is 99.96% accurate from 90 days post contact for detecting HIV 1 and 2 antibodies.  We also have a mobile testing van which is often out in communities providing mobile rapid HIV tests.  Appointments are not always necessary, if you would like a test, please contact us on 0116 2559995