Gender difference in 2-year mortality and immunological response to ART in an HIV-infected Chinese population, 2006-2008

Background

Since it was initiated in 2002, the China Free Antiretroviral Treatment (ART) Program has been progressing from an emergency response to a standardized treatment and care system. As of December 31, 2009, a total of 81,880 patients in 31 provinces, autonomous regions, and special municipalities received free ART. Gender differences, however, in mortality and immunological response to ART in this cohort have never been described.

Objective

To understand whether women and men who enrolled in the China National Free ART Program responded equally well to the treatment.

Methods

A retrospective analysis of the national free ART databases from June 2006–December 2008 was performed. HIV-infected subjects who were 18 years or older, ART naïve at baseline, and on a 3TC regimen enrolled in the program from June 1 to December 31, 2006, were included in this study, then followed up to 2 years.

Results

Among 3457 enrolled subjects who met the inclusion criteria, 59.2% were male and 40.8% female. The majority of the subjects were 19–44 years old (77%) and married (72%). Over the full 24 months of follow-up, the mortality rate was 19.0% in males and 11.4% in females (p = 0.0014). Males on therapy for 3–24 months were more likely to die than females (HR = 1.46, 95% CI: 1.04–2.06, p = 0.0307) after adjusting for baseline characteristics. Compared to men, women had higher CD4+ counts over time after initiating ART (p<0.0001).

Conclusions

Our study showed that women had an overall lower mortality and higher CD4+ counts than men in response to ART treatment, which may be attributed to adherence, biological factors, social, cultural and economic reasons. Further study is needed to explore these factors that might contribute to the gender differences in mortality and immunological response to ART.     

Closing the Gap: Increases in Life Expectancy among Treated HIV-Positive Individuals in the United States and Canada

Background

Combination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000–2007 in the U.S. and Canada.

Methods

Participants were from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), aged ≥20 years and on ART. Mortality rates were calculated using participants'' person-time from January 1, 2000 or ART initiation until death, loss to follow-up, or administrative censoring December 31, 2007. Life expectancy at age 20, defined as the average number of additional years that a person of a specific age will live, provided the current age-specific mortality rates remain constant, was estimated using abridged life tables.

Results

The crude mortality rate was 19.8/1,000 person-years, among 22,937 individuals contributing 82,022 person-years and 1,622 deaths. Life expectancy increased from 36.1 [standard error (SE) 0.5] to 51.4 [SE 0.5] years from 2000–2002 to 2006–2007. Men and women had comparable life expectancies in all periods except the last (2006–2007). Life expectancy was lower for individuals with a history of injection drug use, non-whites, and in patients with baseline CD4 counts <350 cells/mm³.

Conclusions

A 20-year-old HIV-positive adult on ART in the U.S. or Canada is expected to live into their early 70 s, a life expectancy approaching that of the general population. Differences by sex, race, HIV transmission risk group, and CD4 count remain.     

Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial

Background

Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting.

Methods and Findings

We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count ≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log₁₀ copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86–1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68–1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options.

Conclusions

We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00050089","term_id":"NCT00050089"}}NCT00050089     

The Impact of Antiretroviral Therapy on Mortality in HIV Positive People during Tuberculosis Treatment: A Systematic Review and Meta-Analysis

Objective

To quantify the impact of antiretroviral therapy (ART) on mortality in HIV-positive people during tuberculosis (TB) treatment.

Design

We conducted a systematic literature review and meta-analysis. Studies published from 1996 through February 15, 2013, were identified by searching electronic resources (Pubmed and Embase) and conference books, manual searches of references, and expert consultation. Pooled estimates for the outcome of interest were acquired using random effects meta-analysis.

Subjects

The study population included individuals receiving ART before or during TB treatment.

Main Outcome Measures

Main outcome measures were: (i) TB-case fatality ratio (CFR), defined as the proportion of individuals dying during TB treatment and, if mortality in HIV-positive people not on ART was also reported, (ii) the relative risk of death during TB treatment by ART status.

Results

Twenty-one studies were included in the systematic review. Random effects pooled meta-analysis estimated the CFR between 8% and 14% (pooled estimate 11%). Among HIV-positive TB cases, those receiving ART had a reduction in mortality during TB treatment of between 44% and 71% (RR = 0.42, 95%CI: 0.29–0.56).

Conclusion

Starting ART before or during TB therapy reduces the risk of death during TB treatment by around three-fifths in clinical settings. National programmes should continue to expand coverage of ART for HIV positive in order to control the dual epidemic.     

Disinhibition in Risky Sexual Behavior in Men,but Not Women,during Four Years of Antiretroviral Therapy in Rural,Southwestern Uganda

Background

In resource-rich areas, risky sexual behavior (RSB) largely diminishes after initiation of anti-retroviral therapy, with notable exceptions among some populations who perceive a protected benefit from anti-retroviral therapy (ART). Yet, there is limited data about long-term trends in risky sexual behavior among HIV-infected people in sub-Saharan Africa after initiation of anti-retroviral therapy.

Methods

We administered questionnaires every three months to collect sexual behavior data among patients taking ART in southwestern Uganda over four years of follow-up time. We defined RSB as having unprotected sex with an HIV-negative or unknown status partner, or unprotected sex with a casual partner. We fit logistic regression models to estimate changes in RSB by time on ART, with and without adjustment for calendar year and CD4 count.

Results

506 participants were enrolled between 2005 and 2011 and contributed a median of 13 visits and 3.5 years of observation time. The majority were female (70%) and median age was 34 years (interquartile range 29–39). There was a decrease in the proportion of men reporting RSB from the pre-ART visit to the first post-ART visit (16.2 to 4.3%, p<0.01) but not women (14.1 to 13.3%, p = 0.80). With each year of ART, women reported decreasing RSB (OR 0.85 per year, 95%CI 0.74–0.98, p = 0.03). In contrast, men had increasing odds of reporting RSB with each year of ART to near pre-treatment rates (OR 1.41, 95%CI 1.14–1.74, p = 0.001), which was partially confounded by changes in calendar time and CD4 count (AOR = 1.24, 95%CI 0.92–1.67, p = 0.16).

Conclusions

Men in southwestern Uganda reported increasing RSB over four years on ART, to levels approaching pre-treatment rates. Strategies to promote long-term safe sex practices targeted to HIV-infected men on ART might have a significant impact on preventing HIV transmission in this setting.     

Gender differences in immune reconstitution: a multicentric cohort analysis in sub-Saharan Africa

Background

In sub-Saharan Africa, men living with HIV often start ART at more advanced stages of disease and have higher early mortality than women. We investigated gender difference in long-term immune reconstitution.

Methods/Principal Findings

Antiretroviral-naïve adults who received ART for at least 9 months in four HIV programs in sub-Saharan Africa were included. Multivariate mixed linear models were used to examine gender differences in immune reconstitution on first line ART.A total of 21,708 patients (68% women) contributed to 61,912 person-years of follow-up. At ART start,. Median CD4 at ART were 149 [IQR 85–206] for women and 125 cells/µL [IQR 63–187] for men. After the first year on ART, immune recovery was higher in women than in men, and gender-based differences increased by 20 CD4 cells/µL per year on average (95% CI 16–23; P<0.001). Up to 6 years after ART start, patients with low initial CD4 levels experienced similar gains compared to patients with high initial levels, including those with CD4>250cells/µL (difference between patients with <50 cells/µL and those with >250 was 284 cells/µL; 95% CI 272–296; LR test for interaction with time p = 0.63). Among patients with initial CD4 count of 150–200 cells/µL, women reached 500 CD4 cells after 2.4 years on ART (95% CI 2.4–2.5) and men after 4.5 years (95% CI 4.1–4.8) of ART use.

Conclusion

Women achieved better long-term immune response to ART, reaching CD4 level associated with lower risks of AIDS related morbidity and mortality quicker than men.     

High incidence of unplanned pregnancy after antiretroviral therapy initiation: findings from a prospective cohort study in South Africa

Background

Increased fertility rates in HIV-infected women receiving antiretroviral therapy (ART) have been attributed to improved immunological function; it is unknown to what extent the rise in pregnancy rates is due to unintended pregnancies.

Methods

Non-pregnant women ages 18–35 from four public-sector ART clinics in Johannesburg, South Africa, were enrolled into a prospective cohort and followed from August 2009–March 2011. Fertility intentions, contraception and pregnancy status were measured longitudinally at participants'' routine ART clinic visits.

Findings

Of the 850 women enrolled, 822 (97%) had at least one follow-up visit and contributed 745.2 person-years (PY) at-risk for incident pregnancy. Overall, 170 pregnancies were detected in 161 women (incidence rate [IR]: 21.6/100 PY [95% confidence interval (CI): 18.5–25.2]). Of the 170 pregnancies, 105 (62%) were unplanned. Unmet need for contraception was 50% higher in women initiating ART in the past year as compared to women on ART>1 year (prevalence ratio 1.5 [95% CI: 1.1–2.0]); by two years post-ART initiation, nearly one quarter of women had at least one unplanned pregnancy. Cumulative incidence of pregnancy was equally high among recent ART initiators and ART experienced participants: 23.9% [95% CI: 16.4–34.1], 15.9% [12.0–20.8], and 21.0% [16.8–26.1] for women on ART 0–1 yr, >1 yr–2 yrs, and >2 yrs respectively (log-rank, p = 0.54). Eight hormonal contraceptive failures were detected [IR: 4.4 [95% CI: 2.2–8.9], 7/8 among women using injectable methods. Overall 47% (80/170) of pregnancies were not carried to term.

Conclusions

Rates of unintended pregnancies among women on ART are high, including women recently initiating ART with lower CD4 counts and higher viral loads. A substantial burden of pregnancy loss was observed. Integration of contraceptive services and counselling into ART care is necessary to reduce maternal and child health risks related to mistimed and unwanted pregnancies. Further research into injectable contraceptive failures on ART is warranted.     

Adherence to Antiretroviral Therapy and Its Effect on Survival of HIV-Infected Individuals in Jharkhand,India

Introduction

Research in India has extensively examined the factors associated with non-adherence to antiretroviral therapy (ART) with limited focus on examining the relationship between adherence to ART regimen and survival status of HIV infected patients. This study examines the effect of optimal adherence to ART on survival status of HIV infected patients attending ART centers in Jharkhand, India.

Materials and Methods

Data from a cohort of 239 HIV infected individuals who were initiated ART in 2007 were compiled from medical records retrospectively for 36 months. Socio-demographic characteristics, CD4 T cell count, presence of opportunistic infections at the time of ART initiation and ART regimen intake and survival status was collected periodically. Optimal adherence was assessed using pill count methods; patients who took <95% of the specified regimens were identified as non-adherent. Cox-proportional hazard model was used to determine the relative hazards of mortality.

Results

More than three-fourths of the patients were male, on an average 34 year old and median CD4 T cell count was 118 cells/cmm at the time of ART registration. About 57% of the patients registered for ART were found to be adherent to ART. A total of 104 patients died in 358.5 patient-years of observation resulting in a mortality rate of 29 per 100 patient-years (95% confidence interval (CI): 23.9–35.2) and median survival time of 6.5 months (CI: 2.7–10.9). The mortality rate was higher among patients who were non-adherent to ART (64.5, CI: 50.5–82.4) than who were adherent (15.4, CI: 11.3–21.0). The risk of mortality was fourfold higher among individuals who were non-adherent to ART than who were adherent (Adjusted hazard ratio: 3.9, CI: 2.6–6.0).

Conclusion

Adherence to ART is associated with a higher chance of survival of HIV infected patients, ascertaining the need for interventions to improve the ART adherence and early initiation of ART.     

Plasma HIV Viral Rebound following Protocol-Indicated Cessation of ART Commenced in Primary and Chronic HIV Infection

Objectives

The magnitude of HIV viral rebound following ART cessation has consequences for clinical outcome and onward transmission. We compared plasma viral load (pVL) rebound after stopping ART initiated in primary (PHI) and chronic HIV infection (CHI).

Design

Two populations with protocol-indicated ART cessation from SPARTAC (PHI, n = 182) and SMART (CHI, n = 1450) trials.

Methods

Time for pVL to reach pre-ART levels after stopping ART was assessed in PHI using survival analysis. Differences in pVL between PHI and CHI populations 4 weeks after stopping ART were examined using linear and logistic regression. Differences in pVL slopes up to 48 weeks were examined using linear mixed models and viral burden was estimated through a time-averaged area-under-pVL curve. CHI participants were categorised by nadir CD4 at ART stop.

Results

Of 171 PHI participants, 71 (41.5%) rebounded to pre-ART pVL levels, at a median of 50 (95% CI 48–51) weeks after stopping ART. Four weeks after stopping treatment, although the proportion with pVL≥400 copies/ml was similar (78% PHI versus 79% CHI), levels were 0.45 (95% CI 0.26–0.64) log₁₀ copies/ml lower for PHI versus CHI, and remained lower up to 48 weeks. Lower CD4 nadir in CHI was associated with higher pVL after ART stop. Rebound for CHI participants with CD4 nadir >500 cells/mm³ was comparable to that experienced by PHI participants.

Conclusions

Stopping ART initiated in PHI and CHI was associated with viral rebound to levels conferring increased transmission risk, although the level of rebound was significantly lower and sustained in PHI compared to CHI.     

Diminishing availability of publicly funded slots for antiretroviral initiation among HIV-infected ART-eligible patients in Uganda

Background

The impact of flat-line funding in the global scale up of antiretroviral therapy (ART) for HIV-infected patients in Africa has not yet been well described.

Methods

We evaluated ART-eligible patients and patients starting ART at a prototypical scale up ART clinic in Mbarara, Uganda between April 1, 2009 and May 14, 2010 where four stakeholders sponsor treatment – two PEPFAR implementing organizations, the Ugandan Ministry of Health – Global Fund (MOH-GF) and a private foundation named the Family Treatment Fund (FTF). We assessed temporal trends in the number of eligible patients, the number starting ART and tabulated the distribution of the stakeholders supporting ART initiation by month and quartile of time during this interval. We used survival analyses to assess changes in the rate of ART initiation over calendar time.

Findings

A total of 1309 patients who were eligible for ART made visits over the 14 month period of the study and of these 819 started ART. The median number of ART eligible patients each month was 88 (IQR: 74 to 115). By quartile of calendar time, PEPFAR and MOH sponsored 290, 192, 180, and 49 ART initiations whereas the FTF started 1, 2, 1 and 104 patients respectively. By May of 2010 (the last calendar month of observation) FTF sponsored 88% of all ART initiations. Becoming eligible for ART in the 3^rd (HR = 0.58, 95% 0.45–0.74) and 4^th quartiles (HR = 0.49, 95% CI: 0.36–0.65) was associated with delay in ART initiation compared to the first quartile in multivariable analyses.

Interpretation

During a period of flat line funding from multinational donors for ART programs, reductions in the number of ART initiations by public programs (i.e., PEPFAR and MOH-GF) and delays in ART initiation became apparent at the a large prototypical scale-up ART clinic in Uganda.     

Early mortality and AIDS progression despite high initial antiretroviral therapy adherence and virologic suppression in Botswana

Background

Adverse outcomes occurring early after antiretroviral therapy (ART) initiation are common in sub-Saharan Africa, despite reports of high levels of ART adherence in this setting. We sought to determine the relationship between very early ART adherence and early adverse outcomes in HIV-infected adults in Botswana.

Methods

This prospective cohort study of 402 ART-naïve, HIV-infected adults initiating ART at a public HIV clinic in Gaborone, Botswana evaluated the relationship between suboptimal early ART adherence and HIV treatment outcomes in the initial months after ART initiation. Early adherence during the interval between initial ART dispensation and first ART refill was calculated using pill counts. In the primary analysis patients not returning to refill and those with adherence <0.95 were considered to have suboptimal early adherence. The primary outcome was death or loss to follow-up during the first 6 months of ART; a secondary composite outcome included the primary outcome plus incident opportunistic illness (OIs) and virologic failure. We also calculated the percent of early adverse outcomes theoretically attributable to suboptimal early adherence using the population attributable risk percent (PAR%).

Results

Suboptimal early adherence was independently associated with loss to follow-up and death (adjusted OR 2.3, 95% CI 1.1–4.8) and with the secondary composite outcome including incident OIs and virologic failure (adjusted OR 2.6, 95% CI 1.4–4.7). However, of those with early adverse outcomes, less than one-third had suboptimal adherence and approximately two-thirds achieved virologic suppression. The PAR% relating suboptimal early adherence and primary and secondary outcomes were 14.7% and 17.7%, respectively.

Conclusions

Suboptimal early adherence was associated with poor outcomes, but most early adverse outcomes occurred in patients with optimal early adherence. Clinical care and research efforts should focus on understanding early adverse outcomes that occur despite optimal adherence.     

Defective Soil for a Fertile Seed? Altered Endometrial Development Is Detrimental to Pregnancy Success

Background

Synchronous development of the endometrium (to achieve a receptive state) and of the embryo is essential for successful implantation and ongoing pregnancy. Endometrial receptivity exists only for a finite time in a menstrual cycle and the endometrium is refractory to embryo implantation outside of this window. Administration of hormones to stimulate multifollicular development within the ovary, integral to the majority of assisted reproduction (ART) protocols, dramatically alters the hormonal milieu to which the endometrium is exposed versus normal menstrual cycles. Endometrial maturation may be profoundly affected by this altered endocrine environment.

Aim

Compare endometrial histology in fertile women, fertile women undergoing hormonal stimulation for oocyte donation and infertile women undergoing fresh embryo transfers in an ART cycle with further comparisons between women who did or did not become pregnant. Examine the presence of leukocytes and markers of endometrial maturation.

Methods

Endometrial histology was examined by hematoxylin and eosin staining with a semi quantitative scoring method developed to compare histological appearance of tissues. The presence of leukocytes and developmental markers was examined by immunohistochemistry and scored.

Results

Endometrial histology was dramatically altered upon stimulation for ART. However, those women who became pregnant presented with significantly less alterations in histological endometrial maturation. Numbers and activation status of leukocyte populations were also altered within the endometria stimulated for ART, with neutrophils undergoing degranulation, usually observed only pre-menstrually.

Conclusion

We propose that such developmental changes render the endometrium hostile to the embryo and that modifications to ART protocols should be considered to take account of the requirement for endometrial receptivity and hence increase pregnancy rates.     

Outcomes of Antiretroviral Therapy in Vietnam: Results from a National Evaluation

Objectives

Vietnam has significantly scaled up its national antiretroviral therapy (ART) program since 2005. With the aim of improving Vietnam’s national ART program, we conducted an outcome evaluation of the first five years of the program in this concentrated HIV epidemic where the majority of persons enrolled in HIV care and treatment services are people who inject drugs (PWID). The results of this evaluation may have relevance for other national ART programs with significant PWID populations.

Design

Retrospective cohort analysis of patients at 30 clinics randomly selected with probability proportional to size among 120 clinics with at least 50 patients on ART.

Methods

Charts of patients whose ART initiation was at least 6 months prior to the study date were abstracted. Depending on clinic size, either all charts or a random sample of 300 charts were selected. Analyses were limited to treatment-naïve patients. Multiple imputations were used for missing data.

Results

Of 7,587 patient charts sampled, 6,875 were those of treatment-naïve patients (74.4% male, 95% confidence interval [CI]: 72.4–76.5, median age 30, interquartile range [IQR]: 26–34, 62.0% reported a history of intravenous drug use, CI: 58.6–65.3). Median baseline CD4 cell count was 78 cells/mm³ (IQR: 30–162) and 30.4% (CI: 25.8–35.1) of patients were at WHO stage IV. The majority of patients started d4T/3TC/NVP (74.3%) or d4T/3TC/EFV (18.6%). Retention rates after 6, 12, 24, and 36 months were 88.4% (CI: 86.8–89.9), 84.0% (CI: 81.8–86.0), 78.8% (CI: 75.7–81.6), and 74.6% (CI: 69.6–79.0). Median CD4 cell count gains after 6, 12, 24, and 36 months were 94 (IQR: 45–153), 142 (IQR: 78–217), 213 (IQR: 120–329), and 254 (IQR: 135–391) cells/mm³. Patients who were PWID showed significantly poorer retention.

Conclusions

The study showed good retention and immunological response to ART among a predominantly PWID group of patients despite advanced HIV infections at baseline.     

Life Expectancies of South African Adults Starting Antiretroviral Treatment: Collaborative Analysis of Cohort Studies

Background

Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults.

Methods and Findings

Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2–30.2) at age 20 y and 10.1 y (95% CI: 9.3–10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0–39.7) and 14.4 y (95% CI: 13.3–15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1–46.0) if her baseline CD4 count was ≥200 cells/µl, compared to 29.5 y (95% CI: 26.2–33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%–20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations.

Conclusions

South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors'' Summary     

Missed Opportunities for Retention in Pre-ART Care in Cape Town,South Africa

Background

Few studies have evaluated access to and retention in pre-ART care.

Objectives

To evaluate the proportion of People Living With HIV (PLWH) in pre-ART and ART care and factors associated with retention in pre-ART and ART care from a community cohort.

Methods

A cross sectional survey was conducted from February – April 2011. Self reported HIV positive, negative or participants of unknown status completed a questionnaire on their HIV testing history, access to pre-ART and retention in pre-ART and ART care.

Results

872 randomly selected adults who reported being HIV positive in the ZAMSTAR 2010 prevalence survey were included and revisited. 579 (66%) reconfirmed their positive status and were included in this analysis. 380 (66%) had initiated ART with 357 of these (94%) retained in ART care. 199 (34%) had never initiated ART of whom 186 (93%) accessed pre-ART care, and 86 (43%) were retained in pre-ART care. In a univariable analysis none of the factors analysed were significantly associated with retention in care in the pre-ART group. Due to the high retention in ART care, factors associated with retention in ART care, were not analysed further.

Conclusion

Retention in ART care was high; however it was low in pre-ART care. The opportunity exists, if care is better integrated, to engage with clients in primary health care facilities to bring them back to, and retain them in, pre-ART care.     

Incidence of Incisional Hernia after Cesarean Delivery: A Register-Based Cohort Study

Objective

To estimate the incidence of incisional hernias requiring surgical repair after cesarean delivery over a 10-year period.

Methods

This population- and register-based cohort study identified all women in Denmark with no history of previous abdominal surgery who had a cesarean delivery between 1991 and 2000. The cohort was followed from their first until 10 years after their last cesarean delivery within the inclusion period or until the first of the following events: hernia repair, death, emigration, abdominal surgery, or cesarean delivery after the inclusion period. For women who had a hernia repair, hospital records regarding the surgery and previous cesarean deliveries were tracked and manually analyzed to validate the relationship between hernia repair and cesarean delivery. Data were analyzed with a competing risk analysis that included each cesarean delivery.

Results

We identified 57,564 women who had had 68,271 cesarean deliveries during the inclusion period. During follow-up, 134 of these women had a hernia requiring repair. Of these 68 (51% [95% CI 42–60%]) were in a midline incision although the transverse incision was the primary approach at cesarean delivery during the inclusion period. The cumulated incidence of a hernia repair within 10 years after a cesarean delivery was 0.197% (95% CI 0.164–0.234%). The risk of a hernia repair was higher during the first 3 years after a cesarean delivery, with an incidence after 3 years of 0.157% (95% CI 0.127–0.187%).

Conclusions

The overall risk of an incisional hernia requiring surgical repair within 10 years after a cesarean delivery was 2 per 1000 deliveries in a population in which the transverse incision was the primary approach at cesarean delivery.     

Anti-Müllerian Hormone Serum Values and Ovarian Reserve: Can It Predict a Decrease in Fertility after Ovarian Stimulation by ART Cycles?

Background

A variety of indicators of potentially successful ovarian stimulation cycles are available, including biomarkers such as anti-Mullerian hormone. The aim of our study was to confirm the usefulness of serum anti-Mullerian hormone assay in predicting ovarian response and reproductive outcome in women eligible for ART cycles.

Materials

Forty-six women undergoing ART cycles at the Centre for Reproductive Medicine in Parma were recruited from March-to-June 2010. Inclusion criteria: age<42 years; body-mass-index = 20–25; regular menstrual cycles; basal serum FSH concentration <12 IU/L and basal serum estradiol concentration <70 pg/mL. The couples included in our study reported a variety of primary infertility causes. All women underwent FSH stimulation and pituitary suppression (GnRH-agonist/GnRH-antagonist protocols). Women were considered poor-responders if thay had ≤3 oocytes; normal-responders 4–9 oocytes and high-responders ≥10 oocytes. Serum samples for the AMH assays were obtained on the first and last days of stimulation. A P value ≤0.05 was considered statistically significant.

Result

FSH levels increased significantly when AMH levels decreased. The total dose of r-FSH administered to induce ovulation was not correlated to AMH. The number of follicles on the hCG, serum estradiol levels on the hCG-day, and the number of retrieved oocytes were significantly correlated to AMH. The number of fertilized oocytes was significantly correlated to the AMH levels. No significant correlation was found between obtained embryos or transferred embryos and AMH. Basal serum AMH levels were significantly higher than those measured on the hCG-day, which appeared significantly reduced. There was a significant correlation between AMH in normal responders and AMH in both high and poor responders.

Conclusions

Our data confirm the clinical usefulness of AMH in ART-cycles to customize treatment protocols and suggest the necessity of verifying an eventual permanent decrease in AMH levels after IVF.     

Characteristics and Outcomes among Older HIV-Positive Adults Enrolled in HIV Programs in Four Sub-Saharan African Countries

Background

Limited information exists on adults ≥50 years receiving HIV care in sub-Saharan Africa.

Methodology

Using routinely-collected longitudinal patient-level data among 391,111 adults ≥15 years enrolling in HIV care from January 2005–December 2010 and 184,689 initiating ART, we compared characteristics and outcomes between older (≥50 years) and younger adults at 199 clinics in Kenya, Mozambique, Rwanda, and Tanzania. We calculated proportions over time of newly enrolled and active adults receiving HIV care and initiating ART who were ≥50 years; cumulative incidence of loss to follow-up (LTF) and recorded death one year after enrollment and ART initiation, and CD4+ response following ART initiation.

Findings

From 2005–2010, the percentage of adults ≥50 years newly enrolled in HIV care remained stable at 10%, while the percentage of adults ≥50 years newly initiating ART (10% [2005]-12% [2010]), active in follow-up (10% [2005]-14% (2010]), and active on ART (10% [2005]-16% [2010]) significantly increased. One year after enrollment, older patients had significantly lower incidence of LTF (33.1% vs. 32.6%[40–49 years], 40.5%[25–39 years], and 56.3%[15–24 years]; p-value<0.0001), but significantly higher incidence of recorded death (6.0% vs. 5.0% [40–49 years], 4.1% [25–39 years], and 2.8% [15–24 years]; p-valve<0.0001). LTF was lower after vs. before ART initiation for all ages, with older adults experiencing less LTF than younger adults. Among 85,763 ART patients with baseline and follow-up CD4+ counts, adjusted average 12-month CD4+ response for older adults was 20.6 cells/mm³ lower than for adults 25–39 years of age (95% CI: 17.1–24.1).

Conclusions

The proportion of patients who are ≥50 years has increased over time and been driven by aging of the existing patient population. Older patients experienced less LTF, higher recorded mortality and less robust CD4+ response after ART initiation. Increased programmatic attention on older adults receiving HIV care in sub-Saharan Africa is warranted.