The study authors noted that the decrease in life expectancy for HIV-positive men is comparable to the effect of cigarette smoking or having a chronic disease like diabetes.

“Men who have sex with men who are recently infected are estimated to have a good life expectancy, provided they are diagnosed early (and have good access to HIV care),” said Fumiyo Nakagawa, a researcher at UCL Medical School in London and lead author of the study.

“Our model has also estimated that life expectancy is further prolonged if the individual does not smoke, does not interrupt treatment, and has good adherence to treatment,” she added.

Life expectancy refers to the expected number of years of life remaining for an individual at a given age. In the general population, several factors, including sex, race, and lifestyle habits, are known to influence life expectancy. Various factors, like better drugs, earlier detection, and increased experience of physicians in treating HIV, are thought to contribute to increased life expectancy of people with HIV.

A Danish study published earlier this year found that HIV-positive individuals suffer from higher death rates mainly due to HIV and non-HIV related risk factors such as poor response to antiretroviral therapy, co-infection with hepatitis C or other diseases, and drug and alcohol abuse.

According to the study authors, most studies so far have based life expectancy estimates on current death rates in people with HIV. Since drugs’ ability to suppress the amount of HIV in the blood have improved over time, and since therapy benefits on death rates may take years to fully take effect due to slow increases in CD4 (white blood cell) counts, life expectancy for HIV-positive people may have been underestimated.

In this study, researchers used a computer simulation model of HIV infection and the effects of antiretroviral therapy to estimate life expectancy for a man who has sex with men and who becomes HIV positive in 2010 at the age of 30 years old. They also attempted to determine how life expectancy varied depending on how early or late HIV was diagnosed. For comparison, the researchers used general population death rates for men in the United Kingdom for 2009.

The model assumed that a man with HIV would start a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, then switch to a boosted protease inhibitor-based regimen in the case of virologic failure.

The likelihood of treatment interruption was assumed to be 1.5 times higher in individuals with lower treatment adherence. Based on results from previous studies, a 1.5-fold increase in risk for all non-AIDS deaths was assumed for men with HIV throughout life.

Researchers also assumed a 40 percent chance of being a smoker and no hepatitis C co-infection.

Results showed that in a society with a high rate of HIV diagnosis, in which HIV was likely to be diagnosed soon after infection, the median age of death was estimated to be 75 years old. Risk of death within five and 10 years after infection was 2.3 percent and 5.2 percent, respectively. In addition, 57 percent, 78 percent, and 97 percent of men were diagnosed by three, five, and 10 years after infection, respectively.

Under this model, the median time from infection to diagnosis was 2.8 years, and the median CD4 cell count at diagnosis was 432 cells per microliter. In addition, the average time from infection to starting antiretroviral therapy was almost six years. Individuals were estimated to spend an average of 39 years on treatment, of which all but roughly seven years were spent actually receiving antiretroviral therapy (as opposed to periods of interrupted treatment).

The chance of treatment interruption at least once during an individual’s lifetime was estimated at 85 percent. Estimated life expectancy increased by 1.5 years when it was assumed that no treatment interruptions occurred.

It was estimated that 41 percent of individuals will at some stage progress to AIDS. However, only 14 percent of deaths were predicted to be from AIDS-related illnesses, and only 10 percent of men predicted to die of AIDS were also predicted to have resistance to all three major antiretroviral drug classes (nucleoside-reverse transcriptase inhibitors, NNRTIs, and protease inhibitors) plus integrase inhibitors.

Results also showed that in a society with a low HIV diagnosis rate, in which HIV was diagnosed only when symptoms were present, life expectancy for HIV-positive men who have sex with men was 71.5 years, indicating that an average of 10.5 years of life were lost compared to people without HIV.

With a low diagnosis rate, the median CD4 count was 140 cells per microliter at diagnosis; 22 percent, 37 percent, and 74 percent of individuals were diagnosed with HIV within three, five, and 10 years after infection, respectively. Consequently, there was a higher risk of death within 10 years after diagnosis (13 percent compared to 5.2 percent with a high diagnosis rate).

However, the effect of late diagnosis on life expectancy after this time was less significant due to the long-lasting effects of antiretroviral therapy, even in those who start treatment when CD4 cell counts are low.

The researchers estimated that the effect of late diagnosis would be greatest in the first 15 to 20 years after infection. Late diagnoses also increased the probability of transmitting HIV to others because lack of treatment increases risk of HIV transmission.

For more information, please see the study in the journal AIDS (abstract).

The guidelines contain updated recommendations in several areas, including diagnosis of HIV in infants, start of antiretroviral therapy, selection of antiretrovirals, and adherence to antiretroviral therapy in children and teenagers.

The guidelines now also include a rating system to indicate the strength of each recommendation, and formatting changes have been implemented to improve readability. For example, a section on drug side effects in children that includes information on risk factors, symptoms, preventative measures, and treatment options is now presented in a table format for ease of use.

The guidelines are intended for use by doctors and other health care professionals when treating HIV-positive children and teens.

Key updates to various sections of the guidelines are summarized below.

Diagnosis Of HIV In Infants

The guidelines now recommend HIV testing at birth for infants who are at high risk for contracting the virus. This includes babies born to HIV-positive mothers who did not receive prenatal care or prenatal antiretroviral therapy, or who had HIV viral loads (amount of virus in the blood) greater than 1,000 copies per milliliter near the time of delivery.

HIV infection in adults is usually diagnosed by looking for antibodies – proteins made by the immune system to help identify and fight bacteria and viruses. In infants, however, tests for HIV antibodies may lead to false-positive results, as children of this age group often still carry their mothers’ HIV antibodies.

To avoid a false diagnosis, the guidelines continue to recommend tests that detect the virus itself to determine HIV status in infants younger than 18 months. This includes HIV DNA PCR assays and HIV RNA tests, both of which can detect the HIV virus directly.

The guide also continues to recommend that babies be tested for HIV at 14 to 21 days after birth, age 1 to 2 months, and 4 to 6 months of age.

Start Of Antiretroviral Therapy

Suggestions for when to initiate antiretroviral therapy vary according to age group.

Antiretroviral therapy is now recommended for children older than 12 months who have normal CD4 (white blood cell) counts but HIV viral loads of 100,000 copies per milliliter of blood or higher, even if their symptoms are mild or nonexistent.

For children under the age of 12 months, the guidelines continue to recommend starting antiretroviral therapy regardless of CD4 count, viral load, or the presence or absence of symptoms. Several studies have shown that starting therapy early in children of this age significantly reduces the chances a child will progress to AIDS or die.

In children with normal CD4 counts whose HIV viral loads are less than 100,000 copies per milliliter, and who have mild or no symptoms, initiation of treatment can be either considered or deferred.

Selection Of Antiretroviral Drugs For Treatment Naïve Patients

As with adults, all HIV-positive children should be treated using combination therapy that includes at least three different antiretroviral drugs from two different classes.

However, the updated guidelines now indicate that non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy is not recommended for children younger than 3 years of age who have been exposed to single dose Viramune (nevirapine).

Viramune is often used to prevent mother-to-child transmission. Babies who have been exposed to Viramune before birth have a higher risk of drug resistance to Viramune after birth. They may also have a higher chance of treatment failure with NNRTI-based antiretroviral therapy.

For children under 3 years of age who have been exposed to Viramune, the preferred treatment is a Kaletra (lopinavir/ritonavir)-based regimen.

In addition, Viramune is not recommended in girls after puberty who have CD4 counts of 250 cells per microliter or higher, and Sustiva (efavirenz) is not recommended in sexually active teenage girls unless contraception can be reliably guaranteed.

Other antiretrovirals that are not recommended are Viracept (nelfinavir) for children under 2 years of age, Sustiva in children under 3 years of age, and unboosted Prezista (darunavir), Invirase (saquinavir mesylate), or Aptivus (tipranavir).

Drugs that should not be combined in children include Epivir (lamivudine) plus Emtriva (emtricitabine), zidovudine (Retrovir) plus stavudine (Zerit), or dual NNRTI regimens.

The guidelines also recommend against once daily (rather than twice daily) dosing of Kaletra, boosted Prezista, and boosted or unboosted Lexiva (fosamprenavir) in children. Although once-daily doses of these antiretrovirals have been approved in adults, the effectiveness of once-daily dosing versus twice-daily dosing has not been shown in children.

The guide continues to recommend that treatment naïve patients (patients who have never received antiretroviral therapy) complete antiretroviral drug resistance testing before choosing which drugs to use for treatment.

Adherence To Antiretroviral Therapy

Adherence to therapy can often be difficult for children and teenagers. Ensuring that patients follow their treatment regimens is important because missing doses can cause HIV to develop resistance to treatment, leading to treatment failure.

The guidelines now recommend that at least one method to monitor adherence, such as self-reporting of missed doses or pharmacy refill checks, be used in addition to viral load tests.

The updated guidelines also suggest prescribing once-daily antiretroviral therapy when possible rather than twice-daily dosing, since studies in adults have shown once-daily dosages promote better adherence.

For more information, please see the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection (pdf).

This cost-effective method can enhance clinical care for HIV infected adults and children in areas with limited sources. HIV infection can be combated more effectively in infants with early diagnosis and immediate treatment.

Current methods to diagnose and monitor HIV infection in resource limited areas are serological assays, analysis of blood stream, and CD4/CD8 counts. CD4 cells are healthy T4 cells that are the primary target of HIV; CD4 counts can be used as a marker for likely disease progression. However, these methods can diagnose only after eighteen months of age, are costly, and require a great amount of infrastructure.

In the study, a polymerase chain reaction (PCR) assay was used to measure viral loads using RNA extracted from filter paper containing DBS.

PCR is a technique to amplify a single or few copies of DNA, generating millions of copies of a particular DNA sequence. Through amplification, viruses such as HIV can be detected even at a very early stage of infection. This assay is reproducible, accurate, specific, sensitive, and cost effective.

DBS can be prepared either in a laboratory setting or in a clinical setting. Use of DBS provides an efficient and inexpensive method for obtaining blood samples for PCR analysis that minimizes contamination chances without sacrificing sample quality.

In this study, blood samples were collected from 33 HIV-1 positive children who had acquired the infection through mother-to-child transmission. These study participants ranged from 5 to 21 years of age. Additional blood samples were taken from 19 infants born to HIV-1 positive mothers, 4 HIV-1 positive adults, and 44 HIV-1 negative individuals.

PCR testing of DBS samples was found effective in early detection of HIV-1 in infants, the presence of specific antibodies, and drug resistance as well as monitoring viral load (the amount of virus in the blood) in laboratories and clinics that lack the resources for refrigeration or sample processing. Additionally, it is cost-effective and easily adaptable to areas with fewer resources, where the majority of new HIV-1 infections are seen today.

For more information, please visit the original study in PLos One.