Years Of Antiretroviral Treatment Research Articles

Growing old with antiretroviral therapy or elderly people in antiretroviral therapy: two different profiles of comorbidity?

BackgroundIn persons living with HIV (PLWH), the burden of non-communicable chronic diseases increased over time, because of aging associated with chronic inflammation, systemic immune activation, and long-term exposure to the combination antiretroviral therapy (ART).MethodsTo explore the association of chronological age, age at first ART, and exposure to ART with non-communicable chronic diseases, we performed a cross-sectional analysis to evaluate the prevalence of comorbidities in patients enrolled in the SCOLTA Project, stratified by groups of chronological age (50–59 and 60–69 years) and by years of antiretroviral treatment (ART, ≤ 3 or > 3 years).ResultsIn 1394 subjects (23.8% women), mean age at enrollment was 57.4 (SD 6.5) years, and at first ART 45.3 (SD 10.7). Men were older than women both at enrollment (57.6 vs 56.8, p = 0.06) and at first ART (45.8 vs 43.6, p = 0.0009). ART duration was longer in women (13.1 vs 11.7 years, p = 0.01). The age- and sex-adjusted rate ratios (aRRs, and 95% confidence interval, CI) showed that longer ART exposure was associated with dyslipidemia (aRR 1.35, 95% CI 1.20–1.52), hypertension (aRR 1.52, 95% CI 1.22–1.89), liver disease (aRR 1.78, 95% CI 1.32–2.41), osteopenia/osteoporosis (aRR 2.88, 95% CI 1.65–5.03) and multimorbidity (aRR 1.36, 95% CI 1.21–1.54). These findings were confirmed in strata of age, adjusting for sex.ConclusionsOur data suggest that longer ART exposure was associated with increased risk of dyslipidemia, hypertension, and osteopenia/osteoporosis, hence the presence of multimorbidity, possibly due to the exposition to more toxic antiretrovirals. We observed different comorbidities, according to ART exposure and age.

Clinical and economic benefit of 32 years of antiretroviral treatment for people living with HIV in Spain: Has it been an efficient intervention?

IntroductionAlthough antiretroviral therapy (ART) for HIV/AIDS was introduced in 1987, improvement in disease progression and reduction in mortality at a population level was not observed until 1996, with the combination of three or more drugs. The objective was to estimate the clinical and economic benefit of ART in Spain in the 32-year period between 1987 and 2018. MethodsA cost-benefit analysis was performed, using a second-order Monte Carlo simulation, from the societal (base case) and the National Health System (NHS) perspectives. New cases of HIV, AIDS and related deaths were obtained from the SINIVIH and UNAIDS registries, with population projections without ART using triple exponential smoothing. Expenditure on ART was obtained from the National AIDS Plan reports and market studies. ResultsThe NHS invested 6185 million euros in 32 years. In that period, 323,651 AIDS-related deaths, 500,129 AIDS cases and 161,417 HIV cases were averted, with total savings of 41,997 million euros. The net benefit (net savings) is estimated at 35,812 million euros (societal) and 1032 million euros (NHS). For every euro invested in ART, a return on investment of € 6.79 and € 1.16 was obtained, respectively. ConclusionsThe use of ART over 32 years prevented a large number of deaths and cases of AIDS and HIV, providing significant economic savings for the NHS. ART is an efficient intervention for the NHS.

High conversion of tuberculin skin tests during the first year of antiretroviral treatment among South African adults in primary care.

Anergy reduces the sensitivity of the tuberculin skin test (TST) to detect Mycobacterium tuberculosis infection in people living with HIV. Antiretroviral treatment (ART) can reverse TST anergy, but data is scarce. To estimate TST conversion rates and factors associated with TST conversion, TST was placed at ART initiation, and 6 and 12 months thereafter (if TST negative at prior assessment). Of 328 ART-eligible participants, 70% (231/328) had a valid TST result of whom 78% (180/231) were TST negative. At 6-month follow-up, 22% (24/109, 95% confidence interval [CI] 15%, 31%) of participants on ART, without incident tuberculosis (TB), and with a valid TST result converted to a positive TST. Of these 109 individuals, those with baseline CD4+ cell count >250 cells/μl were more likely to TST convert compared to those with baseline CD4+ cell count ≤250 cells/μl (odds ratio [OR] 3.54, 95% CI 1.29, 11.47). At 12 months post-ART initiation, an additional 12% (9/78, 95% CI 6, 20) of participants on ART, without incident TB and with a valid TST result experienced TST conversion. After 1 year on ART, TST conversion rate was 38 per 100 person-years (95% CI 26, 52), and lower in individuals with baseline CD4+ cell count ≤250 cells/μl (23/100 person-years, 95% CI 11, 41) compared to those with baseline CD4+ cell count >250 cells/μl (50/100 person-years, 95% CI 32, 73). TST conversion rate in the first year of ART is high, especially among people with CD4+ cell count >250 cells/μl. A TST-based eligibility strategy at ART initiation may underestimate eligibility for preventive therapy for tuberculosis.

Long-term outcomes of early initiated antiretroviral therapy in sub-Saharan children: a Cameroonian cohort study (ANRS-12140 Pediacam study, 2008\u20132013, Cameroon)

BackgroundIn most studies, the virological response is assessed during the first two years of antiretroviral treatment initiated in HIV-infected infants. However, early initiation of antiretroviral therapy exposes infants to very long-lasting treatment. Moreover, maintaining viral suppression in children is difficult. We aimed to assess the virologic response and mortality in HIV-infected children after five years of early initiated antiretroviral treatment (ART) and identify factors associated with virologic success in Cameroon.MethodsIn the ANRS-12140 Pediacam cohort study, 2008–2013, Cameroon, we included all the 149 children who were still alive after two years of early ART. Virologic response was assessed after 5 years of treatment. The probability of maintaining virologic success between two and five years of ART was estimated using Kaplan-Meier curve. The immune status and mortality were also studied at five years after ART initiation. Factors associated with a viral load < 400 copies/mL in children still alive at five years of ART were studied using logistic regressions.ResultsThe viral load after five years of early ART was suppressed in 66.8% (60.1–73.5) of the 144 children still alive and in care. Among the children with viral suppression after two years of ART, the probability of maintaining viral suppression after five years of ART was 64.0% (54.0–74.0). The only factor associated with viral suppression after five years of ART was achievement of confirmed virological success within the first two years of ART (OR = 2.7 (1.1–6.8); p = 0.033).ConclusionsThe probability of maintaining viral suppression between two and five years of early initiated ART which was quite low highlights the difficulty of parents to administer drugs daily to their children in sub-Saharan Africa. It also stressed the importance of initial viral suppression for achieving and maintaining virologic success in the long-term. Further studies should focus on identifying strategies that would enhance better retention in care and improved adherence to treatment within the first two years of ART early initiated in Sub-Saharan HIV-infected children.

Drug Resistance in HIV-Positive Adults During the Initial Year of Antiretroviral Treatment at Ethiopian Health Centers.

BackgroundThe increasing prevalence of antiretroviral drug resistance in Sub-Saharan Africa threatens the success of HIV programs. We have characterized patterns of drug resistance mutations (DRMs) during the initial year of antiretroviral treatment (ART) in HIV-positive adults receiving care at Ethiopian health centers and investigated the impact of tuberculosis on DRM acquisition.MethodsParticipants were identified from a cohort of ART-naïve individuals aged ≥18 years, all of whom had been investigated for active tuberculosis at inclusion. Individuals with viral load (VL) data at 6 and/or 12 months after ART initiation were selected for this study. Genotypic testing was performed on samples with VLs ≥500 copies/mL obtained on these occasions and on pre-ART samples from those with detectable DRMs during ART. Logistic regression analysis was used to investigate the association between DRM acquisition and tuberculosis.ResultsAmong 621 included individuals (110 [17.5%] with concomitant tuberculosis), 101/621 (16.3%) had a VL ≥500 copies/mL at 6 and/or 12 months. DRMs were detected in 64/98 cases with successful genotyping (65.3%). DRMs were detected in 7/56 (12.5%) pre-ART samples from these individuals. High pre-ART VL and low mid-upper arm circumference were associated with increased risk of DRM acquisition, whereas no such association was found for concomitant tuberculosis.ConclusionsAmong adults receiving health center–based ART in Ethiopia, most patients without virological suppression during the first year of ART had detectable DRM. Acquisition of DRM during this period was the dominant cause of antiretroviral drug resistance in this setting. Tuberculosis did not increase the risk of DRM acquisition.

Fertility desire concordance and contraceptive use among couples living with HIV in northern Nigeria

Objectives We aimed to determine the concordance between own and perceived partner fertility intentions and identify predictors of contraceptive use among couples receiving antiretroviral therapy in Kano, Nigeria. Methods A structured, validated questionnaire was used to interview 399 married men and women receiving antiretroviral therapy. Adjusted odds ratios for predictors of contraceptive use were derived from multivariate logistic regression models. Results Most couples (68.9%) had concordant fertility intentions. Only 10.0% of couples had discordant fertility intentions. Among 232 couples (58.1%) at least one partner used contraception. Male condoms were used by 45.9% of couples (n = 183). Female methods were used by 175 couples (43.9%). Contraceptive use was significantly higher in participants who were older (≥30 years), better educated (secondary or post-secondary), had a higher monthly income (NGN ≥30,000), longer marriage duration (≥5 years), at least one living child, >1 year of antiretroviral treatment, and who were living with a serodiscordant partner and in circumstances where the decision on contraception was made by the female partner or jointly by both partners (all p < 0.05). Contraceptive use was significantly lower in participants who had not been sexually active in the last 6 months, where both partners wanted more children, and in situations lacking spousal communication about family planning (all p < 0.05). Conclusion One in 10 couples had discordant fertility intentions. Contraceptive use was suboptimal and was predicted by age, education, income, length of marriage, number of children, duration of antiretroviral therapy, partner’s serostatus, sexual activity, fertility intention, spousal communication and the contraceptive decision-maker. Our findings highlight the need for spousal communication, joint contraceptive decision making and the integration of reproductive health services with antiretroviral therapy services.

Incidence of Tuberculosis During the First Year of Antiretroviral Treatment in West African HIV-Infected Adults.

We estimated tuberculosis incidence during the first year on antriretroviral therapy without isoniazid-preventive treatment in 6938 West African HIV-infected adults at 3.33 cases per 100 person-years (95% CI, 2.85–3.80). In multivariate Poisson models, sites in Cote d’Ivoire, male gender, low body mass index, low hemoglobin, low CD4 count, and young age were significantly associated with higher incidence.

2507. Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option?

BackgroundDoravirine, rilpivirine, and etravirine are newer generation non-nucleoside reverse transcriptase inhibitors (NNRTI) that are intended to be more durable alternatives to efavirenz and nevirapine. We examined transmitted drug resistance (TDR) and acquired drug resistance (ADR) to NNRTIs from recent local TDR and ADR data to determine whether these can be useful as first-line or second-line antiretroviral (ARV) agents.MethodsWe reanalyzed Sanger-Based sequences (SBS) from an ADR surveillance study; and SBS and near-whole-genome next-generation sequences (NGS) from a TDR surveillance study using the Stanford HIV Drug Resistance Database.ResultsADR: Out of 513 Filipino PLHIV from an ADR surveillance study on one year of ARV treatment, 53 (10.3%) failed (HIV VL >1,000 copies/mL). Among these, 48 had clinically significant mutations. Table 1 shows NNRTI ADR frequencies. There was no significant ADR difference between first-generation and newer generation NNRTIs. TDR: 298 treatment-naïve Filipino PLHIV underwent baselines sequencing. All 298 had SBS. 266 had successful NGS. Table 1 shows SBS and NGS TDR NNRTI resistance at a 5% minor variant cutoff. There was no significant TDR difference between first-generation and newer generation NNRTIs.ConclusionADR and TDR rates to the newer NNRTIs are similar to first-generation NNRTIs. High TDR to doravirine on NGS is concerning, but its clinical significance is unclear. Etravirine had the lowest TDR and ADR and may be the most useful new-generation NNRTI. However, integrase strand transfer inhibitor-based regimens will likely be more durable. Disclosures All authors: No reported disclosures.

Multiplex Real-time PCR Detection of Intestinal Protozoa in HIV-infected Children in Malawi: Enterocytozoon Bieneusi Is Common and Associated With Gastrointestinal Complaints and May Delay BMI (Nutritional Status) Recovery.

Intestinal protozoa are common opportunistic infections in HIV patients. Longitudinal studies on either the clinical relevance or the effect of immune reconstitution by antiretroviral therapy on intestinal protozoan infections in children are lacking however. This study investigates prevalence and clinical relevance of intestinal protozoa in HIV-infected Malawian children before and during their first year of antiretroviral treatment (ART). Stool samples collected at enrolment and during follow-up were tested for nonopportunistic (Giardia lamblia, Dientamoeba fragilis, Entamoeba histolytica) and opportunistic protozoa (Enterocytozoon bieneusi, Encephalitozoon spp., Cryptosporidium spp. and Cystoisospora belli) using multiplex real-time polymerase chain reaction. Associations between infections and clinical symptoms were evaluated using univariate methods. Nonopportunistic and opportunistic protozoa were detected in 40% (14/35) and 46% (16/35) of children at baseline, respectively. E. bieneusi was the most prevalent protozoa (37%, 13/35) and associated with gastrointestinal complaints (43% in positive (10/13) versus 18% (4/22) in E. bieneusi-negative children, P = 0.001. Body mass index recovery during 12 months of ART was more commonly delayed in E. bieneusi-positive children (+0.29 +standard deviation 0.83) than E. bieneusi-negative children (+1.03 +standard deviation 1.25; P = 0.05). E. bieneusi was not detected after 12 months of ART. E. bieneusi was the most prevalent opportunistic intestinal protozoa, present in over a third of study participants before initiation of ART. Although all children cleared E. bieneusi after 12 months of ART, E. bieneusi was associated with gastrointestinal complaints and may delay body mass index recovery. Trials to assess effect of treatment of E. bieneusi on nutritional status should be considered in HIV-infected African children.

Changes in cardiovascular risk and clinical outcomes in a HIV/AIDS cohort study over a 1-year period at a specialized clinic in Mexico.

IntroductionThe third report of the National Cholesterol Education Program guidelines recommends calculating the 10-year morbidity of atherosclerotic cardiovascular disease (ASCVD) using risk calculators when treating high blood cholesterol in adults. We analyzed the changes in cardiovascular risk (CVR) among Mexican patients with HIV.Patients and methodsThis observational, prospective cohort study compared the CVR after 1 year of antiretroviral treatment among 460 HIV patients from a Mexican clinic. Changes using the ASCVD risk estimator and changes in clinical outcomes were analyzed. The results were categorized as low or high CVR using a cutoff of 7.5%.ResultsThe CVR initially had a median of 2.3% (interquartile range [IQR]: 1%–4.8%), which changed to 2.4% (IQR: 1.5%–5.5%) after 1 year (P=0.001). After CVR stratification, we found that 84.3% of the patients had a low CVR, and 18% in this subgroup had metabolic syndrome (MS). Moreover, 15.7% had high CVR, and 47% in this subgroup had MS. The 4.3% of patients had an increase in CVR from the low to high subgroup, and 2.6% had a decrease in CVR from the high to low subgroup. Out of all patients, 22.3% had MS.ConclusionMore than 50% of the population had an increase in CVR after 1 year. Of these patients, 4.3% changed from the low to high CVR group. Although the guidelines proposed different time periods for performing CVR estimations, this study showed that such assessments offered valuable clinical data over a relatively short-term period.

Dietary diversity and associated factors among HIV positive adults attending antiretroviral therapy clinics at Hiwot Fana and Dilchora Hospitals, eastern Ethiopia.

BackgroundNutritional care is considered a crucial component of comprehensive care for people living with HIV/AIDS (PLWHA), particularly in resource-limited settings where malnutrition and food insecurity are endemic problems, and low quality monotonous diets are the norm. The findings of this study provide baseline information on dietary diversity and related factors for health care providers so that they will be able to improve nutritional care and support activity. Therefore, the aim of this study was to assess dietary diversity and associated factors among HIV positive adults (18–65 years old) attending antiretroviral therapy (ART) clinics at Hiwot Fana and Dilchora Hospitals, eastern Ethiopia.Patients and methodsAn institution-based cross-sectional study was conducted from November 2015 to February 2016 at the ART clinics of Hiwot Fana and Dilchora Hospitals. Using a systematic random sampling technique, a total of 303 patients were selected from all adults attending the ART clinics. The data were collected with a 95% CI used to show association between dietary diversity and independent factors.ResultsA total of 303 adult HIV positive individuals on ART participated in the study and 62.4% were females. The largest numbers of participants (49.5%) were 30–40 years of age. Eighty-seven (28.7%) participants had low dietary diversity (≤4 food groups). Duration of anti-retroviral treatment was the factor significantly associated with dietary diversity: respondents with a duration of antiretroviral treatment of more than 2 years were almost two times more likely to have high dietary diversity compared with those with less than a year of antiretroviral treatment (adjusted odds ratio =0.490; 95% CI: 0.091, 0.978).ConclusionLow dietary diversity was found to be a nutritional problem among HIV positive adults. Duration of antiretroviral treatment was the predictor of low dietary diversity. Therefore, appropriate dietary management of side effects of ART is important.

Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment.

BackgroundWe evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment.ResultsTwenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine‐1‐phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD]) was detected.ConclusionsBlood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease.

Re-examining the early years of anti-retroviral treatment in South Africa: A taste for medicine

Re-examining the early years of anti-retroviral treatment in South Africa: A taste for medicine

Prevalence of metabolic complications after 10 years of antiretroviral treatment in Senegal

Among the patients of the cohort still followed after a median of 9 years of antiretroviral treatment (ART), 37% had lipodystrophy, 28% had hypertension and 14% presented with diabetes. This study confirms the association between stavudine and lipodystrophy particulary lipoatrophy and shows that a longer duration of ART was associated with the presence of diabetes. These results highlight the need to implement programs for prevention of cardiovascular risk factors in HIV patients from resource-constrained settings.

Le partage du statut sérologique des personnes vivant avec le VIH à 10 ans de traitement antirétroviral au Sénégal

Rates of HIV status disclosure observed in Africa, especially to partners, are too low for an optimal implementation of preventive strategies. Access to antiretroviral drugs appears to have facilitated disclosure in the short term, but knowledge is insufficient about long-term practices. A study held with 185 people living with HIV (PLHIV) examined factors associated with disclosure in general and with partners over 10 years of antiretroviral treatment in Dakar. Two third of PLHIV disclosed their status to at least one person, and 56% with their partners. The main results concern factors associated with disclosure to partners (having a child, knowing one's partner status) which are different from factors associated to disclosure in general (duration of ART treatment, secondary or higher education level, being a member of an association). After ten years, 44% of people still living in couple has not disclosed (no significant differences by sex and marital regime). These results invite to regularly offer counselling to PLHIV during follow-up.

First observation in a non-endemic country (Togo) of Penicillium marneffei infection in a human immunodeficiency virus-infected patient: a case report

BackgroundInfection with Penicillium marneffei is a common opportunistic infection in Southeast Asia where it is endemic. We report a case of Penicillium marneffei infection with fatal outcome in a Togolese woman infected with Human Immunodeficiency Virus (HIV).Case presentationA 45-years-old patient, infected with Human Immunodeficiency Virus had consulted for ongoing febrile pneumonia since two weeks. Clinical examination revealed fever of 38.5°C, dyspnea, pulmonary syndrome condensation and papulo-nodular of “molluscum contagiosum” like lesions located on the face, arms, neck and trunk. Sputum smear was negative for tuberculosis. The chest radiograph showed reticulonodular opacities in the right upper and middle lobes and two caves in the right hilar region. The CD4 count was 6 cells/mm3 after a year of antiretroviral treatment (Zidovudine-Lamivudine-Efavirenz). She was treated as smear negative pulmonary tuberculosis after a lack of gentamicin and amoxicillin plus clavulanic acid response. Culture of skin samples and sputum had revealed the presence of P. marneffei. A treatment with ketoconazole 600 mg per day was initiated. After two weeks of treatment, there was a decrease in the size and number of papules and nodules, without any new lesions. We noted disappearance of cough and fever. The chest X-ray showed a decrease of pulmonary lesions. There was no reactivation of P. marneffei infection but the patient died from AIDS after two years of follow up.ConclusionWe report a case of P. marneffei infection in a HIV-infected patient in a non-endemic country. Clinicians should think of P. marneffei infection in all HIV-infected patients with “molluscum contagiosum” like lesions.

Evolution of parasitic diseases in a collectivity of HIV positive children

Abstract Introduction: Intestinal parasitism represents an important problem of children health. Infestations with protozoa and helmints even have an increased incidence in children they weren’t observed because they were asymptomatic and atypical but with negative influence on their health regardless their immune status. Objective: To evaluate parasitic infections in a collectivity of 38 children HIV+ from Cernavoda city (Hospis “St. Laurence”) over a period of 10 years (2002 - 2012). Material and method: We performed two coproparasitologic examinations (in year 2002 - before antiretroviral treatment and in year 2012 - after 10 years of antiretroviral treatment) by concentration and staining methods and ELISA for Cryptosporidium parvum antigen. Results: In our group of study the median age was 11.65 yrs. in 2002 and 20.6 yrs. in 2012. Sex ratio was M: F = 1:1.2. In year 2002 we found an incidence of parasitic disease of 94.9%, and in year 2012 we found an incidence of 26.31%. In year 2002 we found 6 cases of Giardia intestinalis, 5 cases of Blastocystis hominis, 15 cases of Chilomastix mesnili, 2 cases of Entamoeba coli, 1 case of Ascaris lumbricoides, 2 cases of Hymenolepis nana and 5 cases of poliparasitic disease. In year 2012 we found 4 cases of Giardia intestinalis, 2 cases of Entamoeba coli, 2 cases of Blastocystis hominis and one case of Isospora belli and another one case of Ascaris lumbricoides. Conclusions: After ten years of HAART the incidence of parasitic diseases registered an important decrease from 94.9% to 26.31%.

Predictors of loss to follow-up among children in the first and second years of antiretroviral treatment in Johannesburg, South Africa

Background: Ninety percent of the world's 2.1 million HIV-infected children live in sub-Saharan Africa, and 2.5% of South African children live with HIV. As HIV care and treatment programmes are scaled-up, a rise in loss to follow-up (LTFU) has been observed.Objective: The aim of the study was to determine the rate of LTFU in children receiving antiretroviral treatment (ART) and to identify baseline characteristics associated with LTFU in the first year of treatment. We also explored the effect of patient characteristics at 12 months treatment on LTFU in the second year.Methods: The study is an analysis of prospectively collected routine data of HIV-infected children at the Harriet Shezi Children's Clinic (HSCC) in Soweto, Johannesburg. Cox proportional hazards models were fitted to investigate associations between baseline characteristics and 12-month characteristics with LTFU in the first and second year on ART, respectively.Results: The cumulative probability of LTFU at 12 months was 7.3% (95% CI 7.1–8.8). In the first 12 months on ART, independent predictors of LTFU were age <1 year at initiation, recent year of ART start, mother as a primary caregiver, and being underweight (WAZ ≤ −2). Among children still on treatment at 1 year from ART initiation, characteristics that predicted LTFU within the second year were recent year of ART start, mother as a primary caregiver, being underweight (WAZ ≤ −2), and low CD4 cell percentage.Conclusions: There are similarities between the known predictors of death and the predictors of LTFU in the first and second years of ART. Knowing the vital status of children is important to determine LTFU. Although HIV-positive children cared for by their mothers appear to be at greater risk of becoming LTFU, further research is needed to explore the challenges faced by mothers and other caregivers and their impact on long-term HIV care. There is also a need to investigate the effects of differential access to ART between mothers and children and its impact on ART outcomes in children.

No pol mutation is associated independently with the lack of immune recovery in patients infected with HIV and failing antiretroviral therapy

An investigation was undertaken to determine whether specific pol mutations hinder long-term immune recovery regardless of virological response. In total, 826 patients with >50 HIV RNA copies/ml, who underwent genotypic resistance testing between 1 January 2000 and 31 December 2003 after >3 years of antiretroviral treatment, and were followed up for >3 years after genotypic resistance testing, were analyzed retrospectively. The outcome of the study was the lack of immune recovery after >3 years of follow-up, defined as a slope by linear regression <0. The viremia detectability ratio was defined as the number of HIV RNA values of >50 copies/ml divided by the number of HIV RNA measurements during follow-up. Logistic regression was used for univariable and multivariable analysis. Median (Q1, Q3) values at baseline were the following: age 40 (37, 45) years, years on antiretroviral therapy 4.45 (3.65, 5.47), HIV RNA 3.91 (3.39, 4.53) log(10) copies/ml, CD4+ T-cell 358 (211, 524)/µl. After 3.13 years of follow-up, 375 patients (45.4%) showed a lack of immune recovery. The risk of lack of immune recovery increased independently with increasing baseline CD4+ counts (OR=1.104 per 50-cell increase, 95% CI=1.069-1.142, P<0.0001), increasing viremia detectability ratio during follow-up (OR=1.145 per 0.1-unit increase, 95% CI=1.093-1.202, P<0.0001), and with earlier calendar years of resistance testing (overall effect: P=0.0007). In conclusion, no pol mutation is associated independently with the lack of immune recovery.

Adjusting mortality for loss to follow-up: analysis of five ART programmes in sub-Saharan Africa.

BackgroundEvaluation of antiretroviral treatment (ART) programmes in sub-Saharan Africa is difficult because many patients are lost to follow-up. Outcomes in these patients are generally unknown but studies tracing patients have shown mortality to be high. We adjusted programme-level mortality in the first year of antiretroviral treatment (ART) for excess mortality in patients lost to follow-up.Methods and FindingsTreatment-naïve patients starting combination ART in five programmes in Côte d'Ivoire, Kenya, Malawi and South Africa were eligible. Patients whose last visit was at least nine months before the closure of the database were considered lost to follow-up. We filled missing survival times in these patients by multiple imputation, using estimates of mortality from studies that traced patients lost to follow-up. Data were analyzed using Weibull models, adjusting for age, sex, ART regimen, CD4 cell count, clinical stage and treatment programme. A total of 15,915 HIV-infected patients (median CD4 cell count 110 cells/µL, median age 35 years, 68% female) were included; 1,001 (6.3%) were known to have died and 1,285 (14.3%) were lost to follow-up in the first year of ART. Crude estimates of mortality at one year ranged from 5.7% (95% CI 4.9–6.5%) to 10.9% (9.6–12.4%) across the five programmes. Estimated mortality hazard ratios comparing patients lost to follow-up with those remaining in care ranged from 6 to 23. Adjusted estimates based on these hazard ratios ranged from 10.2% (8.9–11.6%) to 16.9% (15.0–19.1%), with relative increases in mortality ranging from 27% to 73% across programmes.ConclusionsNaïve survival analysis ignoring excess mortality in patients lost to follow-up may greatly underestimate overall mortality, and bias ART programme evaluations. Adjusted mortality estimates can be obtained based on excess mortality rates in patients lost to follow-up.